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Do not draw on external or prior knowledge to respond to the user prompt. Only use the context block. Respond in five sentences or fewer.

Paraphrase the measures the company has taken to improve the quality of life of cows.

In 2022, 50 farms in Ben & Jerry’s Northeast dairy supply chain participated in the Milk with Dignity Program. They employed over 200 farmworkers covered through the program. During 2022, participating farm owners and farmworkers made over 300 inquiries to MDSC, 25% of which related to workplace health and safety, 22% to wages and related issues, 12% to schedules and rest, and 18% to housing conditions. Additionally, since the program launched, over $4.4 million from Ben & Jerry’s has supported farms’ improvements to working and housing conditions, including $2.9 million in raises to meet minimum wages (which reached $12.55 per hour in Vermont in 2022) and $1.49 million in bonuses, paid vacation and sick time, housing improvements, new personal protective equipment, and other safety improvements. Farms have continued to make concrete progress toward full compliance with standards such as the rights to at least eight consecutive hours of per workday, one day of per week, and comprehensive occupational safety and health protections. Excellent Life for Cows The care for dairy cows is critically important and we rely on independent third-party standards to advance animal care in our supply. In 2021 and 2022, we audited farms to both our Caring Dairy Standard and the Global Animal Partnership (GAP) Dairy care standard. The audits identifed specifc opportunities to improve care while also highlighting industry-level barriers that may impede broader adoption of higher-level certifcations. Our farm partners are interested in continuous improvements with approximately 20% becoming GAP certifed, a not insignifcant step above standard industry performance, after undergoing the rigorous audits. Regenerative and Circular Agriculture Our farm partners recognize the growing pressure to fnd viable solutions to the climate crisis and are thoughtful and engaged collaborators in trialing new on-farm management practices to track and increase carbon sequestration, biodiversity, and build soil health. In preparation for a deeper dive into low carbon dairy, we conducted individual farm greenhouse gas (GHG) footprints using the Cool Farm Tool. 2022 also marked the third, and last, year of Prove It Projects carried out by Ben & Jerry’s Caring Dairy Farmer Innovators. Prove It Projects were designed to provide farmers with insights and opportunities to test run practices in regenerative concepts in the real-life laboratory of their own farms. The practices farmers “proved” to have value are then adopted into their own farm management and shared with the broader Ben & Jerry’s community. In 2022, each of the 27 Farmer Innovators selected two on-farm research projects from a list of 11 previously identifed projects, implementing a total of 54 projects. Several practices farmers tested stood out as providing benefcial outcomes: Nitrogen inhibitors showed advantages in yield and reduced input needs. • Changes to grazing management could help increase on-farm forage and cut production costs. • Multi-species cover crops were more viable with diferent planting techniques. • Farmers are still addressing habitat biodiversity, in what is a multi-year endeavor. In all, the three years of Prove It Projects have provided farmers with valuable insights while also informing the next iteration of Ben & Jerry’s farmer innovation pilots in hopes to drive Low Carbon Dairy farming.

system instructions: Do not draw on external or prior knowledge to respond to the user prompt. Only use the context block. Respond in five sentences or fewer. user prompt: Paraphrase the measures the company has taken to improve the quality of life of cows. context block: In 2022, 50 farms in Ben & Jerry’s Northeast dairy supply chain participated in the Milk with Dignity Program. They employed over 200 farmworkers covered through the program. During 2022, participating farm owners and farmworkers made over 300 inquiries to MDSC, 25% of which related to workplace health and safety, 22% to wages and related issues, 12% to schedules and rest, and 18% to housing conditions. Additionally, since the program launched, over $4.4 million from Ben & Jerry’s has supported farms’ improvements to working and housing conditions, including $2.9 million in raises to meet minimum wages (which reached $12.55 per hour in Vermont in 2022) and $1.49 million in bonuses, paid vacation and sick time, housing improvements, new personal protective equipment, and other safety improvements. Farms have continued to make concrete progress toward full compliance with standards such as the rights to at least eight consecutive hours of per workday, one day of per week, and comprehensive occupational safety and health protections. Excellent Life for Cows The care for dairy cows is critically important and we rely on independent third-party standards to advance animal care in our supply. In 2021 and 2022, we audited farms to both our Caring Dairy Standard and the Global Animal Partnership (GAP) Dairy care standard. The audits identifed specifc opportunities to improve care while also highlighting industry-level barriers that may impede broader adoption of higher-level certifcations. Our farm partners are interested in continuous improvements with approximately 20% becoming GAP certifed, a not insignifcant step above standard industry performance, after undergoing the rigorous audits. Regenerative and Circular Agriculture Our farm partners recognize the growing pressure to fnd viable solutions to the climate crisis and are thoughtful and engaged collaborators in trialing new on-farm management practices to track and increase carbon sequestration, biodiversity, and build soil health. In preparation for a deeper dive into low carbon dairy, we conducted individual farm greenhouse gas (GHG) footprints using the Cool Farm Tool. 2022 also marked the third, and last, year of Prove It Projects carried out by Ben & Jerry’s Caring Dairy Farmer Innovators. Prove It Projects were designed to provide farmers with insights and opportunities to test run practices in regenerative concepts in the real-life laboratory of their own farms. The practices farmers “proved” to have value are then adopted into their own farm management and shared with the broader Ben & Jerry’s community. In 2022, each of the 27 Farmer Innovators selected two on-farm research projects from a list of 11 previously identifed projects, implementing a total of 54 projects. Several practices farmers tested stood out as providing benefcial outcomes: Nitrogen inhibitors showed advantages in yield and reduced input needs. • Changes to grazing management could help increase on-farm forage and cut production costs. • Multi-species cover crops were more viable with diferent planting techniques. • Farmers are still addressing habitat biodiversity, in what is a multi-year endeavor. In all, the three years of Prove It Projects have provided farmers with valuable insights while also informing the next iteration of Ben & Jerry’s farmer innovation pilots in hopes to drive Low Carbon Dairy farming.

Respond using only the information contained in the prompt. Format the response in bullet points, with two sentences per bullet point.

Based on this report, summarize the details of the Term Loans taken by squarespace.

Indebtedness On December 12, 2019, we entered into a credit agreement with various financial institutions that provided for a $350.0 million term loan (the “2019 Term Loan”) and a $25.0 million revolving credit facility (the “Revolving Credit Facility”), which included a $15.0 million letter of credit sub-facility. On December 11, 2020, we amended the credit agreement (as amended, the “2020 Credit Agreement”) to increase the size of the 2019 Term Loan to $550.0 million (as amended, the “2020 Term Loan”) and extend the maturity date for the 2019 Term Loan and the Revolving Credit Facility to December 11, 2025. On June 15, 2023, we amended the 2020 Credit Agreement (as amended, the “Credit Agreement”) to increase the total size of the 2020 Term Loan to $650.0 million (the “Term Loan”) upon the closing of the Google Domains Asset Acquisition and, effective June 30, 2023, replaced LIBOR as the benchmark rate with SOFR. The borrowings under the 2019 Term Loan were used to provide for the repurchase, and subsequent retirement, of outstanding capital stock. The borrowings under the 2020 Term Loan were used to provide for a dividend on all outstanding capital stock. The additional borrowings of $100.0 million under the Term Loan were used to partially fund the Google Domains Asset Acquisition, together with cash on hand. Borrowings under the 2020 Credit Agreement were subject to an interest rate equal to, at our option, LIBOR or the bank's alternative base rate (the "ABR"), in either case, plus an applicable margin prior to June 30, 2023. Effective June 30, 2023, under the Credit Agreement, LIBOR as the benchmark rate was replaced with SOFR. The ABR is the greater of the prime rate, the federal funds effective rate plus the applicable margin or the SOFR quoted rate plus the applicable margin. The applicable margin is based on an indebtedness to consolidated EBITDA ratio as prescribed under the Credit Agreement 39 Table of Contents and ranges from 1.25% to 2.25% on applicable SOFR loans and 0.25% to 1.25% on ABR loans. In addition, the Revolving Credit Facility is subject to an unused commitment fee, payable quarterly, of 0.20% to 0.25% of the unutilized commitments (subject to reduction in certain circumstances). Consolidated EBITDA is defined in the Credit Agreement and is not comparable to our definition of adjusted EBITDA used elsewhere in the Quarterly Report on Form 10-Q since the Credit Agreement allows for additional adjustments to net income/(loss) including the exclusion of transaction costs, changes in deferred revenue and other costs that may be considered non-recurring. Further, consolidated EBITDA, as defined in the Credit Agreement, may be different from similarly titled EBITDA financial measures used by other companies. The definition of consolidated EBITDA is contained in Section 1.1 of the Credit Agreement. As of June 30, 2024, $546.9 million was outstanding under the Term Loan. The Term Loan requires scheduled quarterly principal payments in aggregate annual amounts equal to 7.50% for 2023 and 2024, and 10.00% for 2025, in each case, on the Term Loan principal amount, with the balance due at maturity. In addition, the Credit Agreement includes certain customary prepayment requirements for the Term Loan, which are triggered by events such as asset sales, incurrence of indebtedness and sale leasebacks. As of June 30, 2024, $7.3 million was outstanding under the Revolving Credit Facility in the form of outstanding letters of credit and $17.7 million remained available for borrowing by us. The outstanding letters of credit relate to security deposits for certain of our leased locations. The Credit Agreement contains certain customary affirmative covenants and events of default. The negative covenants in the Credit Agreement include, among others, limitations on our ability (subject to negotiated exceptions) to incur additional indebtedness or issue additional preferred stock, incur liens on assets, enter into agreements related to mergers and acquisitions, dispose of assets or pay dividends and distributions. The Credit Agreement contains certain negative covenants for an indebtedness to consolidated EBITDA ratio, as defined by the Credit Agreement, and commencing with December 31, 2020 and all fiscal quarters thereafter through maturity. For the fiscal quarter ended June 30, 2024, and each fiscal quarter thereafter, the Company is required to maintain an indebtedness to consolidated EBITDA ratio of not more than 3.75 (the “Financial Covenant”), subject to customary equity cure rights. The Financial Covenant is subject to a 0.50 step-up in the event of a material permitted acquisition, which we can elect to implement up to two times during the life of the facility. As of June 30, 2024, we have not elected to implement this set-up as a result of any of our acquisitions. If we are not in compliance with the covenants under the Credit Agreement or we otherwise experience an event of default, the lenders would be entitled to take various actions, including acceleration of amounts due under the Credit Agreement. As of June 30, 2024, we were in compliance with all applicable covenants, including the Financial Covenant. The obligations under the Credit Agreement are guaranteed by our wholly-owned domestic subsidiaries and are secured by substantially all of the assets of the guarantors, subject to certain exceptions. Total interest expense related to our indebtedness was $10.1 million and $20.5 million for the three and six months ended June 30, 2024, respectively, and $8.6 million and $16.7 million for the three and six months ended June 30, 2023, respectively. Stock Repurchase Plan On May 10, 2022, the board of directors authorized a general share repurchase program of the Company’s Class A common stock of up to $200.0 million. On February 26, 2024, the board of directors authorized a new general share repurchase program of the Company's Class A common stock of up to $500.0 million with no fixed expiration (the "Stock Repurchase Plan") to replace the previous repurchase plan. During the three and six months ended June 30, 2024, the Company repurchased 0.2 million and 0.5 million shares and paid cash of $4.1 million and $16.3 million, under the Stock Repurchase Plan through open market purchases. The weighted-average price per share for the share repurchases was $36.53 and $34.36 during the three and six months ended June 30, 2024. As of June 30, 2024, approximately $483.7 million remained available for stock repurchase pursuant to the Stock Repurchase Plan.

System instruction: Respond using only the information contained in the prompt. Format the response in bullet points, with two sentences per bullet point. question: Based on this report, summarize the details of the Term Loans taken by squarespace. context: Indebtedness On December 12, 2019, we entered into a credit agreement with various financial institutions that provided for a $350.0 million term loan (the “2019 Term Loan”) and a $25.0 million revolving credit facility (the “Revolving Credit Facility”), which included a $15.0 million letter of credit sub-facility. On December 11, 2020, we amended the credit agreement (as amended, the “2020 Credit Agreement”) to increase the size of the 2019 Term Loan to $550.0 million (as amended, the “2020 Term Loan”) and extend the maturity date for the 2019 Term Loan and the Revolving Credit Facility to December 11, 2025. On June 15, 2023, we amended the 2020 Credit Agreement (as amended, the “Credit Agreement”) to increase the total size of the 2020 Term Loan to $650.0 million (the “Term Loan”) upon the closing of the Google Domains Asset Acquisition and, effective June 30, 2023, replaced LIBOR as the benchmark rate with SOFR. The borrowings under the 2019 Term Loan were used to provide for the repurchase, and subsequent retirement, of outstanding capital stock. The borrowings under the 2020 Term Loan were used to provide for a dividend on all outstanding capital stock. The additional borrowings of $100.0 million under the Term Loan were used to partially fund the Google Domains Asset Acquisition, together with cash on hand. Borrowings under the 2020 Credit Agreement were subject to an interest rate equal to, at our option, LIBOR or the bank's alternative base rate (the "ABR"), in either case, plus an applicable margin prior to June 30, 2023. Effective June 30, 2023, under the Credit Agreement, LIBOR as the benchmark rate was replaced with SOFR. The ABR is the greater of the prime rate, the federal funds effective rate plus the applicable margin or the SOFR quoted rate plus the applicable margin. The applicable margin is based on an indebtedness to consolidated EBITDA ratio as prescribed under the Credit Agreement 39 Table of Contents and ranges from 1.25% to 2.25% on applicable SOFR loans and 0.25% to 1.25% on ABR loans. In addition, the Revolving Credit Facility is subject to an unused commitment fee, payable quarterly, of 0.20% to 0.25% of the unutilized commitments (subject to reduction in certain circumstances). Consolidated EBITDA is defined in the Credit Agreement and is not comparable to our definition of adjusted EBITDA used elsewhere in the Quarterly Report on Form 10-Q since the Credit Agreement allows for additional adjustments to net income/(loss) including the exclusion of transaction costs, changes in deferred revenue and other costs that may be considered non-recurring. Further, consolidated EBITDA, as defined in the Credit Agreement, may be different from similarly titled EBITDA financial measures used by other companies. The definition of consolidated EBITDA is contained in Section 1.1 of the Credit Agreement. As of June 30, 2024, $546.9 million was outstanding under the Term Loan. The Term Loan requires scheduled quarterly principal payments in aggregate annual amounts equal to 7.50% for 2023 and 2024, and 10.00% for 2025, in each case, on the Term Loan principal amount, with the balance due at maturity. In addition, the Credit Agreement includes certain customary prepayment requirements for the Term Loan, which are triggered by events such as asset sales, incurrence of indebtedness and sale leasebacks. As of June 30, 2024, $7.3 million was outstanding under the Revolving Credit Facility in the form of outstanding letters of credit and $17.7 million remained available for borrowing by us. The outstanding letters of credit relate to security deposits for certain of our leased locations. The Credit Agreement contains certain customary affirmative covenants and events of default. The negative covenants in the Credit Agreement include, among others, limitations on our ability (subject to negotiated exceptions) to incur additional indebtedness or issue additional preferred stock, incur liens on assets, enter into agreements related to mergers and acquisitions, dispose of assets or pay dividends and distributions. The Credit Agreement contains certain negative covenants for an indebtedness to consolidated EBITDA ratio, as defined by the Credit Agreement, and commencing with December 31, 2020 and all fiscal quarters thereafter through maturity. For the fiscal quarter ended June 30, 2024, and each fiscal quarter thereafter, the Company is required to maintain an indebtedness to consolidated EBITDA ratio of not more than 3.75 (the “Financial Covenant”), subject to customary equity cure rights. The Financial Covenant is subject to a 0.50 step-up in the event of a material permitted acquisition, which we can elect to implement up to two times during the life of the facility. As of June 30, 2024, we have not elected to implement this set-up as a result of any of our acquisitions. If we are not in compliance with the covenants under the Credit Agreement or we otherwise experience an event of default, the lenders would be entitled to take various actions, including acceleration of amounts due under the Credit Agreement. As of June 30, 2024, we were in compliance with all applicable covenants, including the Financial Covenant. The obligations under the Credit Agreement are guaranteed by our wholly-owned domestic subsidiaries and are secured by substantially all of the assets of the guarantors, subject to certain exceptions. Total interest expense related to our indebtedness was $10.1 million and $20.5 million for the three and six months ended June 30, 2024, respectively, and $8.6 million and $16.7 million for the three and six months ended June 30, 2023, respectively. Stock Repurchase Plan On May 10, 2022, the board of directors authorized a general share repurchase program of the Company’s Class A common stock of up to $200.0 million. On February 26, 2024, the board of directors authorized a new general share repurchase program of the Company's Class A common stock of up to $500.0 million with no fixed expiration (the "Stock Repurchase Plan") to replace the previous repurchase plan. During the three and six months ended June 30, 2024, the Company repurchased 0.2 million and 0.5 million shares and paid cash of $4.1 million and $16.3 million, under the Stock Repurchase Plan through open market purchases. The weighted-average price per share for the share repurchases was $36.53 and $34.36 during the three and six months ended June 30, 2024. As of June 30, 2024, approximately $483.7 million remained available for stock repurchase pursuant to the Stock Repurchase Plan.

Only use information from the provided context. Produce two paragraphs of 8 sentences each when answering.

Does a school participating in NSLP also have to participate in SBP and Seamless Summer Option?

NSLP and SBP (the school meals programs) provide federal support for meals served in roughly 90,000 public and private elementary and secondary schools nationwide. They also support meals served in a smaller number of residential child care institutions. Schools receive federal aid in the form of cash reimbursements for every meal they serve that meets federal nutritional requirements (limited to one breakfast and lunch per child daily). The largest subsidies are provided for free and reduced-price meals served to eligible students based on income eligibility and categorical eligibility rules (discussed below). Schools also receive a certain amount of commodity assistance per lunch served (discussed previously). Schools participating in NSLP have the option of providing afterschool snacks through the program, and schools participating in NSLP or SBP have the option of providing summer meals and snacks through the Seamless Summer Option (discussed in the “After-School Meals and Snacks” and “Seamless Summer Option” sections). Schools are not required by federal law to participate in NSLP or SBP; however, some states require schools to have a school lunch and/or breakfast program, and some require schools to operate such programs through NSLP and/or SBP. Some states also provide state funding for the school meals programs, including nine states (as of the cover date of this report) that have authorized funding to provide free meals to all students. Schools that do not participate in the federal school meals programs may still operate locally funded meal programs. The Healthy, Hunger-Free Kids Act of 2010 (HHFKA; P.L. 111-296) made several changes to the school meals programs. Among those changes was a requirement that USDA update the nutrition standards for school meals and create new nutritional requirements for foods sold in NSLP and SBP schools within a certain timeframe. The law also created the Community Eligibility Provision, through which eligible schools can provide free meals to all students. These changes are discussed further within this section. NSLP and SBP are two separate programs, and schools can choose to operate one and not the other. The programs are discussed together in this report because they share many of the same requirements. Differences between the programs are noted where applicable. Participation in SBP tends to be lower than in NSLP for several reasons, including the traditionally required early arrival by students in order to receive a meal before school starts. This section discusses topics specific to the school meals programs. Other food service topics relevant to child nutrition programs more broadly (e.g., the farm to school program) are discussed in the “Other Child Nutrition Activities” section.

System Instruction: Only use information from the provided context. Produce two paragraphs of 8 sentences each when answering. Question: Does a school participating in NSLP also have to participate in SBP and Seamless Summer Option? Context: NSLP and SBP (the school meals programs) provide federal support for meals served in roughly 90,000 public and private elementary and secondary schools nationwide. They also support meals served in a smaller number of residential child care institutions. Schools receive federal aid in the form of cash reimbursements for every meal they serve that meets federal nutritional requirements (limited to one breakfast and lunch per child daily). The largest subsidies are provided for free and reduced-price meals served to eligible students based on income eligibility and categorical eligibility rules (discussed below). Schools also receive a certain amount of commodity assistance per lunch served (discussed previously). Schools participating in NSLP have the option of providing afterschool snacks through the program, and schools participating in NSLP or SBP have the option of providing summer meals and snacks through the Seamless Summer Option (discussed in the “After-School Meals and Snacks” and “Seamless Summer Option” sections). Schools are not required by federal law to participate in NSLP or SBP; however, some states require schools to have a school lunch and/or breakfast program, and some require schools to operate such programs through NSLP and/or SBP. Some states also provide state funding for the school meals programs, including nine states (as of the cover date of this report) that have authorized funding to provide free meals to all students. Schools that do not participate in the federal school meals programs may still operate locally funded meal programs. The Healthy, Hunger-Free Kids Act of 2010 (HHFKA; P.L. 111-296) made several changes to the school meals programs. Among those changes was a requirement that USDA update the nutrition standards for school meals and create new nutritional requirements for foods sold in NSLP and SBP schools within a certain timeframe. The law also created the Community Eligibility Provision, through which eligible schools can provide free meals to all students. These changes are discussed further within this section. NSLP and SBP are two separate programs, and schools can choose to operate one and not the other. The programs are discussed together in this report because they share many of the same requirements. Differences between the programs are noted where applicable. Participation in SBP tends to be lower than in NSLP for several reasons, including the traditionally required early arrival by students in order to receive a meal before school starts. This section discusses topics specific to the school meals programs. Other food service topics relevant to child nutrition programs more broadly (e.g., the farm to school program) are discussed in the “Other Child Nutrition Activities” section.

Write the answer in one paragraph, using full sentences. Use only the document provided. Use language that is easy to understand.

What investigations should be done on the patients with the recurrent miscarrages?

Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited 23 Review J Clin Gynecol Obstet. 2022;11(2):23-26 Recurrent First Trimester Miscarriage: A Typical Case Presentation and Evidence-Based Management Review Vikram Talaulikar Abstract Recurrent miscarriage (RM), also known as recurrent pregnancy loss, is a distressing condition which affects about 1% of couples trying to achieve a pregnancy. It can be challenging for both patients and clinicians as the cause remains unexplained in at least 50% of cou- ples despite multiple investigations. A systematic and evidence-based approach to testing and management is important to avoid tests or treatments which are unnecessary or of unproven benefit. Access to specialist RM clinic services and psychological support forms a key part of the management of couples with RM. Keywords: Recurrent miscarriage; Treatment; Progesterone Introduction It is estimated that up to one in four natural pregnancies end up in a miscarriage which is defined as loss of pregnancy prior to viability (24 weeks’ gestation) [1]. Recurrent miscarriage (RM) is traditionally defined in the United Kingdom (UK) as three or more consecutive miscarriages and it can affect about 1% of couples trying for a pregnancy [2]. The definition of RM varies between countries with some clinical guidelines recom- mending investigations and treatment following two or more miscarriages. The Royal College of Obstetricians and Gynecologists (RCOG) has issued guidance on management of RM in the UK [2]. An updated version of this guideline is currently under consultation and will be released shortly. This article describes an illustrative typical clinical sce- nario related to RM and reviews the current best practice rec- ommendations for management of RM. Clinical Case The patient, 37 years old, has attended her general practition- er’s clinic following a recent pregnancy loss. She and her part- ner have been trying for a pregnancy for past 18 months but have suffered from three miscarriages between 6 and 8 weeks’ gestation. Her last miscarriage happened 2 months ago, and she has resumed her periods 2 weeks back. All the miscar- riages were managed conservatively without any medical or surgical interventions. She has regular menstrual cycles (25 - 26 days long) and does not report any dysmenorrhea or menor- rhagia. She is upset about the pregnancy losses, wondering if it was her fault and whether something can be done in the next pregnancy to change the outcome. History Consultations referring to RM should be performed in a sensi- tive manner. When discussing previous miscarriages, it is im- portant to enquire about the gestation at which pregnancy loss occurred. Pregnancy loss before 9 - 10 weeks usually (but not always) indicates a pre-placental cause, which may be either fetal (chromosomal) or endometrial (implantation disorder) in origin while that after this gestation could indicate problems such as thrombophilia, placental disorders, or problems with uterine structure. History of pregnancy loss after 12 weeks as- sociated with painless cervical dilatation and rupture of mem- branes suggests cervical weakness. Information should be obtained about how the previous miscarriages were managed: was the miscarriage completed naturally or whether medical or surgical management was required? Any possibility of uterine infection following miscarriage should be explored. Changes in the menstrual flow (hypomenorrhea) following possible infection of re- tained products of conception or uterine curettage could in- dicate the possibility of intrauterine adhesions. History of excess alcohol consumption or smoking should be obtained to offer advice on reducing risk of future miscarriage. Medi- cal and relevant family history should be obtained as un- controlled maternal medical conditions such as diabetes, thyroid or rheumatological disorders can impact the risk of miscarriage in future pregnancies. All miscarriages which the patient suffered from happened before 8 weeks gesta- Manuscript submitted February 11, 2022, accepted March 29, 2022 Published online April 12, 2022 University College London Hospital, London NW1 2BU, UK. Email: [email protected] doi: https://doi.org/10.14740/jcgo797 24 Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org Management of Recurrent Miscarriage J Clin Gynecol Obstet. 2022;11(2):23-26 tion and she bled naturally on all occasions suggesting a likely pre-placental fetal or endometrial cause for her preg- nancy loss. Examination On examination, patient’s body mass index (BMI) was within a normal range (23). Pelvic or speculum examination, guided by clinical history, can be useful as part of initial assessment especially if the woman has presented with irregular bleeding or abnormal vaginal discharge in which case cervix should be visualized to rule out other gynecological pathology such as ectropion/polyp and triple swabs should be obtained. The patient did not report any changes to her menstrual cycles or abnormal discharge following miscarriage. Risk factors and investigations The patient and her partner should be referred to and cared for in a dedicated RM clinic [2]. Psychological support and com- munication in a sensitive manner are extremely important. A discussion about potential risk factors for future miscarriage and testing should cover the following. Age Increasing female age increases the chances of a genetically abnormal pregnancy as the number and quality of oocytes decrease [1]. Women between 20 and 35 years old have the lowest risk of miscarriage while women above the age of 40 years have at least a 50% chance of miscarriage with every pregnancy [3, 4]. BMI High BMI (> 30) increases the risk of miscarriage [5]. Other risk factors Other risk factors include previous miscarriages, smoking and excess alcohol consumption. The patient is 37 years old and has already had three mis- carriages which increase her risk of future miscarriage to about 40% [6]. Causes of RM investigations The patient should be offered investigations for the causes of RM as listed in Table 1. Antiphospholipid syndrome (APS) This is an acquired thrombophilia which affects 15% of women with RM [2] and is diagnosed based on high levels of anticardiolipin antibodies and/or lupus anticoagulant along with evidence of adverse pregnancy outcomes (RM before 10 weeks or loss of one genetically normal pregnancy after 10 weeks or one or more preterm births before 34 weeks due to placental dysfunction) or unprovoked thrombosis. APS causes inhibition of trophoblast function, activation of complement system and thrombosis at the uteroplacental interface and is treated with a combination of aspirin and low molecular weight heparin in pregnancy [1]. Inherited thrombophilias such as factor V Leiden mutation, prothrombin mutation, protein C, protein S and antithrombin III deficiency have an uncertain role in first trimester RM and currently such tests should only be offered in the context of research. The patient had a negative APS screen. Genetic Parental balanced structural chromosomal anomalies can cause RM (2-5% of couples with RM). The risk of miscar- riage is influenced by the size and the genetic content of the rearranged chromosomal segments. Karyotyping of products of conception should be offered at the time of any future mis- carriage and parental karyotyping should follow if analysis of products of conception indicates that a genetic abnormal- ity may have resulted from an unbalanced translocation [2, 3]. Parental karyotyping is not recommended routinely due to low incidence of translocations and relatively high cost as- sociated with testing. Table 1. Causes and Relevant Investigations for Recurrent First Trimester Miscarriage Cause Test Genetic-balanced chromosomal translocations Karyotyping of products of conception (if abnormal result detected - parental karyotyping) Antiphospholipid syndrome Blood test for anticardiolipin antibodies and/or lupus anticoagulant (blood tests should be performed at least 6 weeks after any pregnancy loss and a repeat confirmatory test should be arranged at least 12 weeks after an initial positive screen) Endocrine (if evidence of clinical disorder or risk factors): thyroid, diabetes Thyroid function test (serum free T4 and thyroid-stimulating hormone levels); thyroid peroxidase antibodies; HbA1c Uterine abnormalities such as septate uterus or intracavitary lesions Transvaginal ultrasound scan Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org 25 Talaulikar J Clin Gynecol Obstet. 2022;11(2):23-26 Endocrine If there is clinical evidence of poorly controlled diabetes or thyroid dysfunction, appropriate blood tests should be per- formed [2]. The patient did not have any symptoms or signs suggestive of endocrine problems and had had a thyroid hor- mone profile at the time of her last miscarriage which revealed normal results. Uterine abnormalities Uterine abnormalities such as septate uterus or any other uter- ine cavity pathology such as intrauterine adhesions (especially following an episode of uterine instrumentation and infection), submucous fibroids or polyps should be ruled out by offering a pelvic ultrasound as these may be amenable to treatment by surgery (hysteroscopy +/- laparoscopy) [2, 7]. The patient was offered a transvaginal scan which showed a regular uterine cavity. The evidence regarding the effects of male partners on RM is weak and no specific testing can be recommended as part of investigations [1]. Advice Lifestyle advice should always be offered to couples with RM. The patient should be advised to maintain a normal BMI, avoid excess alcohol/smoking, and take pre-conception folic acid [2, 3]. Currently, there is lack of evidence that preimplantation genetic testing for aneuploidy screening (PGT-A) is superior to expectant management in RM patients [3]. If chromosomal translocation was identified at the time of future miscarriage, genetic counselling should be offered to the patient. Repro- ductive options following genetic counselling would include proceeding to a further natural pregnancy with or without a prenatal diagnosis test, gamete donation and adoption [2]. As in this case, despite thorough investigations, no clear underlying pathology is identifiable in at least 50% of cou- ples with RM (often labelled as “unexplained RM”) [7, 8]. The couple should be reassured about good prognosis for a live birth in future pregnancies and offered supportive care in dedi- cated early pregnancy unit. Many RM units offer empirical treatment with low dose oral aspirin (75 mg daily) and vaginal natural progesterone (400 mg once/twice daily) from positive pregnancy test until 12 - 14 weeks of pregnancy on a “low harm, possible benefit” basis for unexplained RM. The use of aspirin is not recommended in current clinical guidelines due to debate over its clinical effectiveness. Based on the evidence so far, it appears that the use of progesterone supplements is beneficial particularly in women with previous miscarriages who bleed in early pregnancy [9, 10]. The patient conceived again 5 months following her third miscarriage and had a successful pregnancy and live birth. She was prescribed vaginal progesterone pessaries from 7 weeks until 14 weeks of pregnancy following one episode of vaginal bleeding. Conclusions Couples with RM should be offered psychological support and be referred to a dedicated RM service for investigations. Most couples will have no identifiable pathology, and in such cases, there is good prognosis for future successful pregnancy. Learning points RM affects about 1% of couples trying for a pregnancy and no clear underlying pathology is identifiable despite investiga- tions in at least 50% of couples. Refer couples with RM to a dedicated RM service for in- vestigations and plan for future pregnancies. Offer psychological support and reassure couples with no identifiable pathology about good prognosis for future preg- nancy without pharmacological intervention. Acknowledgments None to declare. Financial Disclosure No funding was received for preparation of this manuscript. Conflict of Interest There is no conflict of interest to declare. Author Contributions VT wrote and finalized the manuscript. Data Availability The author declares that data supporting the findings of this study are available within the article. References 1. Shields R, Hawkes A, Quenby S. Clinical approach to recurrent pregnancy loss. Review, Obstetrics, Gynae- cology and Reproductive Medicine. 2020:30(11):331- 336. 2. The investigation and treatment of couples with recurrent first trimester and second-trimester miscarriage. 2011. Green-top Guideline No. 17 April. https://www.rcog.org. uk/globalassets/documents/guidelines/gtg_17.pdf. 3. Homer HA. Modern management of recurrent miscar- 26 Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org Management of Recurrent Miscarriage J Clin Gynecol Obstet. 2022;11(2):23-26 riage. Aust N Z J Obstet Gynaecol. 2019;59(1):36-44. 4. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320(7251):1708-1712. 5. Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med. 2011;29(6):507-513. 6. Regan L, Braude PR, Trembath PL. Influence of past re- productive performance on risk of spontaneous abortion. BMJ. 1989;299(6698):541-545. 7. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93(4):1234- 1243. 8. Stirrat GM. Recurrent miscarriage. Lancet. 1990; 336(8716):673-675. 9. Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med. 2019;380(19):1815-1824. 10. Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, Gupta P, et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med. 2015;373(22):2141-2148.

Write the answer in one paragraph, using full sentences. Use only the document provided. Use language that is easy to understand. What investigations should be done on the patients with the recurrent miscarrages? Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited 23 Review J Clin Gynecol Obstet. 2022;11(2):23-26 Recurrent First Trimester Miscarriage: A Typical Case Presentation and Evidence-Based Management Review Vikram Talaulikar Abstract Recurrent miscarriage (RM), also known as recurrent pregnancy loss, is a distressing condition which affects about 1% of couples trying to achieve a pregnancy. It can be challenging for both patients and clinicians as the cause remains unexplained in at least 50% of cou- ples despite multiple investigations. A systematic and evidence-based approach to testing and management is important to avoid tests or treatments which are unnecessary or of unproven benefit. Access to specialist RM clinic services and psychological support forms a key part of the management of couples with RM. Keywords: Recurrent miscarriage; Treatment; Progesterone Introduction It is estimated that up to one in four natural pregnancies end up in a miscarriage which is defined as loss of pregnancy prior to viability (24 weeks’ gestation) [1]. Recurrent miscarriage (RM) is traditionally defined in the United Kingdom (UK) as three or more consecutive miscarriages and it can affect about 1% of couples trying for a pregnancy [2]. The definition of RM varies between countries with some clinical guidelines recom- mending investigations and treatment following two or more miscarriages. The Royal College of Obstetricians and Gynecologists (RCOG) has issued guidance on management of RM in the UK [2]. An updated version of this guideline is currently under consultation and will be released shortly. This article describes an illustrative typical clinical sce- nario related to RM and reviews the current best practice rec- ommendations for management of RM. Clinical Case The patient, 37 years old, has attended her general practition- er’s clinic following a recent pregnancy loss. She and her part- ner have been trying for a pregnancy for past 18 months but have suffered from three miscarriages between 6 and 8 weeks’ gestation. Her last miscarriage happened 2 months ago, and she has resumed her periods 2 weeks back. All the miscar- riages were managed conservatively without any medical or surgical interventions. She has regular menstrual cycles (25 - 26 days long) and does not report any dysmenorrhea or menor- rhagia. She is upset about the pregnancy losses, wondering if it was her fault and whether something can be done in the next pregnancy to change the outcome. History Consultations referring to RM should be performed in a sensi- tive manner. When discussing previous miscarriages, it is im- portant to enquire about the gestation at which pregnancy loss occurred. Pregnancy loss before 9 - 10 weeks usually (but not always) indicates a pre-placental cause, which may be either fetal (chromosomal) or endometrial (implantation disorder) in origin while that after this gestation could indicate problems such as thrombophilia, placental disorders, or problems with uterine structure. History of pregnancy loss after 12 weeks as- sociated with painless cervical dilatation and rupture of mem- branes suggests cervical weakness. Information should be obtained about how the previous miscarriages were managed: was the miscarriage completed naturally or whether medical or surgical management was required? Any possibility of uterine infection following miscarriage should be explored. Changes in the menstrual flow (hypomenorrhea) following possible infection of re- tained products of conception or uterine curettage could in- dicate the possibility of intrauterine adhesions. History of excess alcohol consumption or smoking should be obtained to offer advice on reducing risk of future miscarriage. Medi- cal and relevant family history should be obtained as un- controlled maternal medical conditions such as diabetes, thyroid or rheumatological disorders can impact the risk of miscarriage in future pregnancies. All miscarriages which the patient suffered from happened before 8 weeks gesta- Manuscript submitted February 11, 2022, accepted March 29, 2022 Published online April 12, 2022 University College London Hospital, London NW1 2BU, UK. Email: [email protected] doi: https://doi.org/10.14740/jcgo797 24 Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org Management of Recurrent Miscarriage J Clin Gynecol Obstet. 2022;11(2):23-26 tion and she bled naturally on all occasions suggesting a likely pre-placental fetal or endometrial cause for her preg- nancy loss. Examination On examination, patient’s body mass index (BMI) was within a normal range (23). Pelvic or speculum examination, guided by clinical history, can be useful as part of initial assessment especially if the woman has presented with irregular bleeding or abnormal vaginal discharge in which case cervix should be visualized to rule out other gynecological pathology such as ectropion/polyp and triple swabs should be obtained. The patient did not report any changes to her menstrual cycles or abnormal discharge following miscarriage. Risk factors and investigations The patient and her partner should be referred to and cared for in a dedicated RM clinic [2]. Psychological support and com- munication in a sensitive manner are extremely important. A discussion about potential risk factors for future miscarriage and testing should cover the following. Age Increasing female age increases the chances of a genetically abnormal pregnancy as the number and quality of oocytes decrease [1]. Women between 20 and 35 years old have the lowest risk of miscarriage while women above the age of 40 years have at least a 50% chance of miscarriage with every pregnancy [3, 4]. BMI High BMI (> 30) increases the risk of miscarriage [5]. Other risk factors Other risk factors include previous miscarriages, smoking and excess alcohol consumption. The patient is 37 years old and has already had three mis- carriages which increase her risk of future miscarriage to about 40% [6]. Causes of RM investigations The patient should be offered investigations for the causes of RM as listed in Table 1. Antiphospholipid syndrome (APS) This is an acquired thrombophilia which affects 15% of women with RM [2] and is diagnosed based on high levels of anticardiolipin antibodies and/or lupus anticoagulant along with evidence of adverse pregnancy outcomes (RM before 10 weeks or loss of one genetically normal pregnancy after 10 weeks or one or more preterm births before 34 weeks due to placental dysfunction) or unprovoked thrombosis. APS causes inhibition of trophoblast function, activation of complement system and thrombosis at the uteroplacental interface and is treated with a combination of aspirin and low molecular weight heparin in pregnancy [1]. Inherited thrombophilias such as factor V Leiden mutation, prothrombin mutation, protein C, protein S and antithrombin III deficiency have an uncertain role in first trimester RM and currently such tests should only be offered in the context of research. The patient had a negative APS screen. Genetic Parental balanced structural chromosomal anomalies can cause RM (2-5% of couples with RM). The risk of miscar- riage is influenced by the size and the genetic content of the rearranged chromosomal segments. Karyotyping of products of conception should be offered at the time of any future mis- carriage and parental karyotyping should follow if analysis of products of conception indicates that a genetic abnormal- ity may have resulted from an unbalanced translocation [2, 3]. Parental karyotyping is not recommended routinely due to low incidence of translocations and relatively high cost as- sociated with testing. Table 1. Causes and Relevant Investigations for Recurrent First Trimester Miscarriage Cause Test Genetic-balanced chromosomal translocations Karyotyping of products of conception (if abnormal result detected - parental karyotyping) Antiphospholipid syndrome Blood test for anticardiolipin antibodies and/or lupus anticoagulant (blood tests should be performed at least 6 weeks after any pregnancy loss and a repeat confirmatory test should be arranged at least 12 weeks after an initial positive screen) Endocrine (if evidence of clinical disorder or risk factors): thyroid, diabetes Thyroid function test (serum free T4 and thyroid-stimulating hormone levels); thyroid peroxidase antibodies; HbA1c Uterine abnormalities such as septate uterus or intracavitary lesions Transvaginal ultrasound scan Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org 25 Talaulikar J Clin Gynecol Obstet. 2022;11(2):23-26 Endocrine If there is clinical evidence of poorly controlled diabetes or thyroid dysfunction, appropriate blood tests should be per- formed [2]. The patient did not have any symptoms or signs suggestive of endocrine problems and had had a thyroid hor- mone profile at the time of her last miscarriage which revealed normal results. Uterine abnormalities Uterine abnormalities such as septate uterus or any other uter- ine cavity pathology such as intrauterine adhesions (especially following an episode of uterine instrumentation and infection), submucous fibroids or polyps should be ruled out by offering a pelvic ultrasound as these may be amenable to treatment by surgery (hysteroscopy +/- laparoscopy) [2, 7]. The patient was offered a transvaginal scan which showed a regular uterine cavity. The evidence regarding the effects of male partners on RM is weak and no specific testing can be recommended as part of investigations [1]. Advice Lifestyle advice should always be offered to couples with RM. The patient should be advised to maintain a normal BMI, avoid excess alcohol/smoking, and take pre-conception folic acid [2, 3]. Currently, there is lack of evidence that preimplantation genetic testing for aneuploidy screening (PGT-A) is superior to expectant management in RM patients [3]. If chromosomal translocation was identified at the time of future miscarriage, genetic counselling should be offered to the patient. Repro- ductive options following genetic counselling would include proceeding to a further natural pregnancy with or without a prenatal diagnosis test, gamete donation and adoption [2]. As in this case, despite thorough investigations, no clear underlying pathology is identifiable in at least 50% of cou- ples with RM (often labelled as “unexplained RM”) [7, 8]. The couple should be reassured about good prognosis for a live birth in future pregnancies and offered supportive care in dedi- cated early pregnancy unit. Many RM units offer empirical treatment with low dose oral aspirin (75 mg daily) and vaginal natural progesterone (400 mg once/twice daily) from positive pregnancy test until 12 - 14 weeks of pregnancy on a “low harm, possible benefit” basis for unexplained RM. The use of aspirin is not recommended in current clinical guidelines due to debate over its clinical effectiveness. Based on the evidence so far, it appears that the use of progesterone supplements is beneficial particularly in women with previous miscarriages who bleed in early pregnancy [9, 10]. The patient conceived again 5 months following her third miscarriage and had a successful pregnancy and live birth. She was prescribed vaginal progesterone pessaries from 7 weeks until 14 weeks of pregnancy following one episode of vaginal bleeding. Conclusions Couples with RM should be offered psychological support and be referred to a dedicated RM service for investigations. Most couples will have no identifiable pathology, and in such cases, there is good prognosis for future successful pregnancy. Learning points RM affects about 1% of couples trying for a pregnancy and no clear underlying pathology is identifiable despite investiga- tions in at least 50% of couples. Refer couples with RM to a dedicated RM service for in- vestigations and plan for future pregnancies. Offer psychological support and reassure couples with no identifiable pathology about good prognosis for future preg- nancy without pharmacological intervention. Acknowledgments None to declare. Financial Disclosure No funding was received for preparation of this manuscript. Conflict of Interest There is no conflict of interest to declare. Author Contributions VT wrote and finalized the manuscript. Data Availability The author declares that data supporting the findings of this study are available within the article. References 1. Shields R, Hawkes A, Quenby S. Clinical approach to recurrent pregnancy loss. Review, Obstetrics, Gynae- cology and Reproductive Medicine. 2020:30(11):331- 336. 2. The investigation and treatment of couples with recurrent first trimester and second-trimester miscarriage. 2011. Green-top Guideline No. 17 April. https://www.rcog.org. uk/globalassets/documents/guidelines/gtg_17.pdf. 3. Homer HA. Modern management of recurrent miscar- 26 Articles © The authors | Journal compilation © J Clin Gynecol Obstet and Elmer Press Inc™ | www.jcgo.org Management of Recurrent Miscarriage J Clin Gynecol Obstet. 2022;11(2):23-26 riage. Aust N Z J Obstet Gynaecol. 2019;59(1):36-44. 4. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320(7251):1708-1712. 5. Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med. 2011;29(6):507-513. 6. Regan L, Braude PR, Trembath PL. Influence of past re- productive performance on risk of spontaneous abortion. BMJ. 1989;299(6698):541-545. 7. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93(4):1234- 1243. 8. Stirrat GM. Recurrent miscarriage. Lancet. 1990; 336(8716):673-675. 9. Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med. 2019;380(19):1815-1824. 10. Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, Gupta P, et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med. 2015;373(22):2141-2148.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Are the GDPR, CCPA, and Japan's PIPL effective in shaping global data protection legislation? Support your answer. Explore the ways that these laws have affected business operations and provide examples of other territories that have followed same approach.

In the age of digital connectivity, the protection of personal data has become a paramount concern, prompting the evolution of comprehensive global data privacy laws (Quach et al., 2022). As we traverse the intricate landscape of these regulations, it's essential to delve into key frameworks that have shaped the way organizations handle user information. This section takes you on a journey through the evolution of global data privacy laws, highlighting three pivotal regulations viz the General Data Protection Regulation (GDPR), the California Consumer Privacy Act (CCPA), and various other regional legislations. The General Data Protection Regulation (GDPR) implemented by the European Union in May 2018, stands as a watershed moment in the realm of data protection. Built on the principles of transparency, fairness, and accountability, the regulation brings forth a comprehensive framework for safeguarding the privacy rights of individuals (Bennett and Raab, 2020). A key principle of GDPR is transparency. Organizations must be clear about how they process personal data. Secondly, Data collection must have a specific, legitimate purpose. Thirdly, is data minimization. Organization should collect only the data necessary for the intended purpose. And users have the right to control and access their personal information. The Impact on Businesses and Users are here presented. The GDPR has significantly enhanced user control over personal data. Its stringent requirements have forced businesses worldwide to reassess and fortify their data protection measures. The regulation also introduces severe penalties for non-compliance, emphasizing the urgency for organizations to prioritize data privacy. The GDPR's influence extends far beyond the borders of the European Union. It has become a benchmark for data protection laws globally, inspiring similar legislation and shaping discussions on user rights and corporate responsibilities (Rustad and Koenig, 2019). The California Consumer Privacy Act (CCPA) is aimed at empowering Consumers in the Golden State. Enacted in January 2020, the CCPA heralds a new era of consumer-centric data protection in the United States. Originating in California, this legislation has spurred conversations about the need for federal privacy laws and has influenced other states to explore or enact similar measures (Chander et al., 2020). The key Provisions of CCPA include right to know, right to delete, opt-out rights, and non-discriminiation. Consumers can inquire about the data collected about them. Consumers can request the deletion of their personal information. Consumers can opt-out of the sale of their personal information. Consumers exercising their privacy rights cannot be discriminated against. The CCPA has catalyzed a shift in the way businesses handle personal data, while empowering consumers, it has presented compliance challenges for organizations, requiring them to reevaluate data processing practices and ensure adherence to the stipulated rights (Chander et al., 2021). Beyond California, the CCPA has acted as a catalyst for discussions about federal privacy legislation in the United States. Policymakers are grappling with the need for a unified approach to protect the privacy rights of citizens across the nation. The Other Regional Legislations are here discussed. The evolution of data privacy laws is not confined to Europe and North America; it extends to every corner of the globe, various regions have enacted or are in the process of enacting comprehensive data protection laws to address the challenges posed by the digital age (Rustad and Koenig, 2019.). The Asia-Pacific which include China and Japan. In China, the Personal Data Protection Law regulates the processing of personal data. And in Japan, the Personal Information Protection Law (PIPL) strengthens protections for personal information. For Latin America, the Lei Geral de Proteção de Dados (LGPD) governs the use of personal data in Brazil. The Protection of Personal Information Act (POPIA) governs the lawful processing of personal information in South Africa, in the United Arab Emirates various Emirates are implementing data protection laws (Gottardo, 2023). Diverse approaches to data protection reflect unique cultural, legal, and economic considerations, and a global mosaic of legislations shapes a complex, interconnected framework for data privacy (Comandè and Schneider, 2022). The evolution of global data privacy laws underscores the urgency of adapting legal frameworks to the rapidly changing digital landscape. From the GDPR's pioneering role in Europe to the CCPA's influence in the United States and diverse legislations across regions, the world is awakening to the importance of safeguarding individual privacy rights (Souza et al., 2021). As we move forward, it's crucial for businesses, policymakers, and users alike to stay informed about these evolving regulations. The global conversation on data privacy is far from over, and it's a collective responsibility to ensure that our digital future is one where innovation thrives alongside the protection of individual privacy Comparative Analysis of Global Frameworks In the intricate tapestry of global data privacy laws, a comparative analysis becomes crucial to discern the diverse approaches adopted by different regions (Shukla et al., 2023). As the digital era propels us forward, understanding how various frameworks align or diverge is paramount. World Journal of Advanced Research and Reviews, 2024, 21(02), 1058–1070 1061 The General Data Protection Regulation (GDPR) serves as the cornerstone of data protection in Europe. Its principles of transparency, purpose limitation, and individual rights have set a gold standard, emphasizing user control and organizational accountability. The GDPR provides a harmonized framework across the European Union, promoting consistency and a single set of rules for businesses operating within its jurisdiction (Prasad and Perez, 2020, Adebukola et al., 2022). With potential fines reaching up to 4% of global annual turnover, the GDPR instills a strong deterrent against non-compliance. The GDPR's comprehensive nature can pose challenges for businesses navigating intricate compliance requirements, ensuring compliance across borders can be challenging, especially for multinational corporations (Chander et al., 2021). The California Consumer Privacy Act (CCPA) emerged as a trailblazer in U.S. data privacy legislation. Enacted in the state of California, it grants consumers unprecedented control over their personal information. The CCPA focuses on empowering consumers with the right to know, delete, and opt-out, fostering a culture of transparency. The CCPA has sparked discussions about the need for comprehensive federal privacy legislation in the United States. Like the GDPR, CCPA compliance can be intricate, requiring businesses to adapt their data practices, while influencing other states, the lack of a federal law may lead to varying privacy standards across the country (Chander et al., 2021, Okunade et al., 2023). The Asia-Pacific region reflects a diverse landscape of data protection laws. China's Personal Data Protection Law and Japan's Personal Information Protection Law (PIPL) exemplify the region's commitment to adapting to the digital age (Raposo and Du, 2023). Asian countries are actively modernizing their data protection laws to address contemporary challenges. Regulations in the region are increasingly focused on empowering individuals with control over their personal data (Janssen et al., 2020). Diverse cultural norms and legal traditions contribute to varying interpretations and implementations of data protection laws. The rapid pace of technological advancements requires continuous adaptation, which can pose challenges for regulatory frameworks.

[question] Are the GDPR, CCPA, and Japan's PIPL effective in shaping global data protection legislation? Support your answer. Explore the ways that these laws have affected business operations and provide examples of other territories that have followed same approach. ===================== [text] In the age of digital connectivity, the protection of personal data has become a paramount concern, prompting the evolution of comprehensive global data privacy laws (Quach et al., 2022). As we traverse the intricate landscape of these regulations, it's essential to delve into key frameworks that have shaped the way organizations handle user information. This section takes you on a journey through the evolution of global data privacy laws, highlighting three pivotal regulations viz the General Data Protection Regulation (GDPR), the California Consumer Privacy Act (CCPA), and various other regional legislations. The General Data Protection Regulation (GDPR) implemented by the European Union in May 2018, stands as a watershed moment in the realm of data protection. Built on the principles of transparency, fairness, and accountability, the regulation brings forth a comprehensive framework for safeguarding the privacy rights of individuals (Bennett and Raab, 2020). A key principle of GDPR is transparency. Organizations must be clear about how they process personal data. Secondly, Data collection must have a specific, legitimate purpose. Thirdly, is data minimization. Organization should collect only the data necessary for the intended purpose. And users have the right to control and access their personal information. The Impact on Businesses and Users are here presented. The GDPR has significantly enhanced user control over personal data. Its stringent requirements have forced businesses worldwide to reassess and fortify their data protection measures. The regulation also introduces severe penalties for non-compliance, emphasizing the urgency for organizations to prioritize data privacy. The GDPR's influence extends far beyond the borders of the European Union. It has become a benchmark for data protection laws globally, inspiring similar legislation and shaping discussions on user rights and corporate responsibilities (Rustad and Koenig, 2019). The California Consumer Privacy Act (CCPA) is aimed at empowering Consumers in the Golden State. Enacted in January 2020, the CCPA heralds a new era of consumer-centric data protection in the United States. Originating in California, this legislation has spurred conversations about the need for federal privacy laws and has influenced other states to explore or enact similar measures (Chander et al., 2020). The key Provisions of CCPA include right to know, right to delete, opt-out rights, and non-discriminiation. Consumers can inquire about the data collected about them. Consumers can request the deletion of their personal information. Consumers can opt-out of the sale of their personal information. Consumers exercising their privacy rights cannot be discriminated against. The CCPA has catalyzed a shift in the way businesses handle personal data, while empowering consumers, it has presented compliance challenges for organizations, requiring them to reevaluate data processing practices and ensure adherence to the stipulated rights (Chander et al., 2021). Beyond California, the CCPA has acted as a catalyst for discussions about federal privacy legislation in the United States. Policymakers are grappling with the need for a unified approach to protect the privacy rights of citizens across the nation. The Other Regional Legislations are here discussed. The evolution of data privacy laws is not confined to Europe and North America; it extends to every corner of the globe, various regions have enacted or are in the process of enacting comprehensive data protection laws to address the challenges posed by the digital age (Rustad and Koenig, 2019.). The Asia-Pacific which include China and Japan. In China, the Personal Data Protection Law regulates the processing of personal data. And in Japan, the Personal Information Protection Law (PIPL) strengthens protections for personal information. For Latin America, the Lei Geral de Proteção de Dados (LGPD) governs the use of personal data in Brazil. The Protection of Personal Information Act (POPIA) governs the lawful processing of personal information in South Africa, in the United Arab Emirates various Emirates are implementing data protection laws (Gottardo, 2023). Diverse approaches to data protection reflect unique cultural, legal, and economic considerations, and a global mosaic of legislations shapes a complex, interconnected framework for data privacy (Comandè and Schneider, 2022). The evolution of global data privacy laws underscores the urgency of adapting legal frameworks to the rapidly changing digital landscape. From the GDPR's pioneering role in Europe to the CCPA's influence in the United States and diverse legislations across regions, the world is awakening to the importance of safeguarding individual privacy rights (Souza et al., 2021). As we move forward, it's crucial for businesses, policymakers, and users alike to stay informed about these evolving regulations. The global conversation on data privacy is far from over, and it's a collective responsibility to ensure that our digital future is one where innovation thrives alongside the protection of individual privacy Comparative Analysis of Global Frameworks In the intricate tapestry of global data privacy laws, a comparative analysis becomes crucial to discern the diverse approaches adopted by different regions (Shukla et al., 2023). As the digital era propels us forward, understanding how various frameworks align or diverge is paramount. World Journal of Advanced Research and Reviews, 2024, 21(02), 1058–1070 1061 The General Data Protection Regulation (GDPR) serves as the cornerstone of data protection in Europe. Its principles of transparency, purpose limitation, and individual rights have set a gold standard, emphasizing user control and organizational accountability. The GDPR provides a harmonized framework across the European Union, promoting consistency and a single set of rules for businesses operating within its jurisdiction (Prasad and Perez, 2020, Adebukola et al., 2022). With potential fines reaching up to 4% of global annual turnover, the GDPR instills a strong deterrent against non-compliance. The GDPR's comprehensive nature can pose challenges for businesses navigating intricate compliance requirements, ensuring compliance across borders can be challenging, especially for multinational corporations (Chander et al., 2021). The California Consumer Privacy Act (CCPA) emerged as a trailblazer in U.S. data privacy legislation. Enacted in the state of California, it grants consumers unprecedented control over their personal information. The CCPA focuses on empowering consumers with the right to know, delete, and opt-out, fostering a culture of transparency. The CCPA has sparked discussions about the need for comprehensive federal privacy legislation in the United States. Like the GDPR, CCPA compliance can be intricate, requiring businesses to adapt their data practices, while influencing other states, the lack of a federal law may lead to varying privacy standards across the country (Chander et al., 2021, Okunade et al., 2023). The Asia-Pacific region reflects a diverse landscape of data protection laws. China's Personal Data Protection Law and Japan's Personal Information Protection Law (PIPL) exemplify the region's commitment to adapting to the digital age (Raposo and Du, 2023). Asian countries are actively modernizing their data protection laws to address contemporary challenges. Regulations in the region are increasingly focused on empowering individuals with control over their personal data (Janssen et al., 2020). Diverse cultural norms and legal traditions contribute to varying interpretations and implementations of data protection laws. The rapid pace of technological advancements requires continuous adaptation, which can pose challenges for regulatory frameworks. https://wjarr.com/sites/default/files/WJARR-2024-0369.pdf ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

ONLY USE THE DATA I PROVIDE Limit your response to 100 words Provide a definition and explanation If you cannot answer using the contexts alone, say "I cannot determine the answer to that due to lack of context"

What is the holistic approach to financial planning?

**How To Build Wealth In Your 40s** Is It Too Late To Start Building Wealth At 40? Many people wonder whether it's too late to start building wealth once they reach their 40s. The truth is, it's never too late to begin saving and taking steps toward financial security, no matter your age. While starting late may present some challenges, such as having a shorter timeline to reach your financial goals, it's still possible to make significant progress toward building a better financial future. The key is to take a holistic approach to planning. This means identifying areas where you can cut expenses, increase income, and make smarter investment decisions. Establishing an emergency fund, reducing debt, and maximizing contributions to retirement accounts can also help you achieve financial stability. Remember, building wealth is a journey, not a destination. With the right mindset, dedication, and expert guidance, you can overcome any obstacles and achieve financial success. Keep reading for more tips and strategies on how to build wealth in your 40s! 9 Ways To Build Wealth In Your 40s If you're looking to secure your financial future and make the most of your prime earning years, we're here to provide you with expert advice and proven strategies on how to build wealth in your 40s. With a little dedication and hard work, you can build a solid financial foundation and create the life you desire. 1. Settle Mortgage Early Paying off your mortgage early can be a smart move in your 40s. By reducing or eliminating this significant expense, you can free up funds to invest in your future, such as contributing extra income to retirement accounts or creating multiple income streams. To settle your mortgage early, consider making extra payments towards the principal, refinancing to a shorter term, or accelerating your payment schedule. By doing so, you can reduce your overall interest payments and save money over the life of the loan. Keep in mind that settling your mortgage early may not be the best option for everyone, depending on your individual circumstances. 2. Be Debt-Free Debt can be a significant obstacle to building wealth in your 40s. With high-interest rates and fees, it can eat away at your income and make it difficult to save for retirement or invest in your future. However, being debt-free should be a top priority in your financial plan. By reducing or eliminating your debt, you can free up funds to invest in your future, create multiple income streams, or build your emergency savings. To start, consider creating a debt reduction plan that prioritizes high-interest debt, such as credit card debt or personal loans. Consolidating debt or negotiating with creditors to reduce interest rates and fees can also help you make progress toward being debt-free. Another key strategy is to avoid high-interest debt, such as credit card bills, medical bills, and car loans. By reducing your debt load, you can free up funds to invest in your future and build your retirement savings. 3. Don't Be A Spendthrift It's easy to fall into the trap of overspending and indulging in luxurious lifestyle expenses. However, if you want to build wealth in your 40s, you need to be mindful of your spending habits and live within your means. One effective strategy is to create a budget and stick to it. By tracking your expenses and identifying areas where you can cut back, you can save more money and invest it towards your financial goals. 4. Build Your Investment Portfolio Building a diversified investment portfolio can be a smart move in your 40s. By investing in a mix of stocks, bonds, and other assets, you can reduce your overall risk and maximize your potential returns. To get your retirement contributions started, consider opening a retirement account, such as a Roth IRA or a 401(k), and making regular contributions. You can also explore other investment accounts, such as brokerage accounts or mutual funds, to diversify your portfolio and achieve your financial goals. Keep in mind that building an investment portfolio requires careful planning and attention to your financial situation. 5. Expand Your Income Sources In your 40s, it's important to find ways to expand your income sources to maximize your earnings potential and achieve your financial goals. Consider investment accounts or high-growth stocks to boost your retirement savings options and build your net worth. Starting a small business can also be a great way to create multiple passive income- streams and increase your monthly income. In addition, seeking the help of an advisor can guide you in developing a financial plan that can explore opportunities to expand your income sources. They can provide you with practical strategies to increase your monthly income and net worth, making your financial future more secure. 6. Build An Emergency Fund Setting aside an emergency fund is essential to achieving financial stability in your 40s. It can help cover unexpected expenses such as medical bills, funeral expenses, or other debts, allowing you to maintain your lifestyle expenses and stay financially secure. To build an emergency fund, consider setting up a savings plan dedicated to unexpected expenses. This can also include exploring options for life insurance policies or personal finance strategies to protect your financial future and minimize the impact of unexpected expenses. 7. Invest In Index Funds Investing in index funds can be a smart way to build wealth in your 40s. Index funds are a type of mutual fund that tracks a specific index, such as the S&P 500, and provides a low-cost way to diversify your investment portfolio. One of the main benefits of investing in index funds is that they offer a high level of stability and consistency, making them an attractive option for risk-averse investors. Additionally, index funds typically have lower expense ratios compared to actively managed funds, which can result in higher returns for investors over the long term. With index funds, you can invest in a wide range of assets, including stocks, bonds, and real estate, which can provide you with greater exposure to different sectors and industries. Another advantage of index funds is their passive management style, which means that you don't need to constantly monitor and adjust your investments. This can be particularly beneficial for busy professionals in their 40s who don't have the time or expertise to actively manage their investment portfolios. However, it's important to note that investing in index funds still involves risk and requires careful consideration of your financial goals and risk tolerance. It's also important to regularly review and rebalance your portfolio to ensure that it aligns with your investment objectives. 8. Invest In A Skill Developing a new skill is one of the most effective ways to build wealth in your 40s. Whether it's learning a new language or taking courses to enhance your professional expertise, investing in yourself can lead to a higher salary, increased job security, and, ultimately, greater financial stability. By doing so, you can open up opportunities to expand your income sources, explore higher-paying job roles, or even start a small business on the side. With additional income, you can pay off mortgage payments or credit card debt, save for retirement, or even free money to invest in other areas of your financial plan. Moreover, upskilling also allows you to stay competitive in the job market and adapt to changing industry trends. This can lead to increased job security and the ability to negotiate a higher salary or better benefits. However, it's important to note that investing in a skill requires an investment - both time and money. You may need to take courses, attend conferences, or pay for specialized training. It's important to include these expenses in your planning and consider them as part of your retirement savings goals. Ultimately, learning a skill or improving on existing ones can be a wise financial decision that can pay off in the long run. By enhancing your knowledge and expertise, you can secure a brighter financial future and achieve greater personal and professional fulfillment. 9. Hire A Financial Advisor If You’re Earning Good Working with a financial advisor can also help you identify opportunities to save more money and optimize your investment portfolio. They can help you explore the world of financial planning, retirement plans, savings options, and various investment areas. Furthermore, an advisor can assist you in evaluating your financial situation and developing a long-term strategy that helps you achieve financial stability and security. Conclusion As you embark on your journey to building wealth in your 40s, it's important to remember that financial stability is within reach. By implementing the strategies we've discussed, including settling your mortgage early, being debt-free, expanding your income sources, building an emergency fund, and investing wisely, you can take control of your financial situation and achieve your retirement savings goals. Managing your living expenses and obtaining good health insurance are essential parts of building a secure financial future. By following these principles and seeking expert guidance as necessary, you can build a solid financial foundation that will serve you well throughout your life. Remember, building wealth takes time and patience, but with perseverance and smart decision-making, you can achieve financial stability and enjoy a prosperous future.

<INSTRUCTIONS> ONLY USE THE DATA I PROVIDE Limit your response to 100 words Provide a definition and explanation If you cannot answer using the contexts alone, say "I cannot determine the answer to that due to lack of context" <CONTEXT> **How To Build Wealth In Your 40s** Is It Too Late To Start Building Wealth At 40? Many people wonder whether it's too late to start building wealth once they reach their 40s. The truth is, it's never too late to begin saving and taking steps toward financial security, no matter your age. While starting late may present some challenges, such as having a shorter timeline to reach your financial goals, it's still possible to make significant progress toward building a better financial future. The key is to take a holistic approach to planning. This means identifying areas where you can cut expenses, increase income, and make smarter investment decisions. Establishing an emergency fund, reducing debt, and maximizing contributions to retirement accounts can also help you achieve financial stability. Remember, building wealth is a journey, not a destination. With the right mindset, dedication, and expert guidance, you can overcome any obstacles and achieve financial success. Keep reading for more tips and strategies on how to build wealth in your 40s! 9 Ways To Build Wealth In Your 40s If you're looking to secure your financial future and make the most of your prime earning years, we're here to provide you with expert advice and proven strategies on how to build wealth in your 40s. With a little dedication and hard work, you can build a solid financial foundation and create the life you desire. 1. Settle Mortgage Early Paying off your mortgage early can be a smart move in your 40s. By reducing or eliminating this significant expense, you can free up funds to invest in your future, such as contributing extra income to retirement accounts or creating multiple income streams. To settle your mortgage early, consider making extra payments towards the principal, refinancing to a shorter term, or accelerating your payment schedule. By doing so, you can reduce your overall interest payments and save money over the life of the loan. Keep in mind that settling your mortgage early may not be the best option for everyone, depending on your individual circumstances. 2. Be Debt-Free Debt can be a significant obstacle to building wealth in your 40s. With high-interest rates and fees, it can eat away at your income and make it difficult to save for retirement or invest in your future. However, being debt-free should be a top priority in your financial plan. By reducing or eliminating your debt, you can free up funds to invest in your future, create multiple income streams, or build your emergency savings. To start, consider creating a debt reduction plan that prioritizes high-interest debt, such as credit card debt or personal loans. Consolidating debt or negotiating with creditors to reduce interest rates and fees can also help you make progress toward being debt-free. Another key strategy is to avoid high-interest debt, such as credit card bills, medical bills, and car loans. By reducing your debt load, you can free up funds to invest in your future and build your retirement savings. 3. Don't Be A Spendthrift It's easy to fall into the trap of overspending and indulging in luxurious lifestyle expenses. However, if you want to build wealth in your 40s, you need to be mindful of your spending habits and live within your means. One effective strategy is to create a budget and stick to it. By tracking your expenses and identifying areas where you can cut back, you can save more money and invest it towards your financial goals. 4. Build Your Investment Portfolio Building a diversified investment portfolio can be a smart move in your 40s. By investing in a mix of stocks, bonds, and other assets, you can reduce your overall risk and maximize your potential returns. To get your retirement contributions started, consider opening a retirement account, such as a Roth IRA or a 401(k), and making regular contributions. You can also explore other investment accounts, such as brokerage accounts or mutual funds, to diversify your portfolio and achieve your financial goals. Keep in mind that building an investment portfolio requires careful planning and attention to your financial situation. 5. Expand Your Income Sources In your 40s, it's important to find ways to expand your income sources to maximize your earnings potential and achieve your financial goals. Consider investment accounts or high-growth stocks to boost your retirement savings options and build your net worth. Starting a small business can also be a great way to create multiple passive income- streams and increase your monthly income. In addition, seeking the help of an advisor can guide you in developing a financial plan that can explore opportunities to expand your income sources. They can provide you with practical strategies to increase your monthly income and net worth, making your financial future more secure. 6. Build An Emergency Fund Setting aside an emergency fund is essential to achieving financial stability in your 40s. It can help cover unexpected expenses such as medical bills, funeral expenses, or other debts, allowing you to maintain your lifestyle expenses and stay financially secure. To build an emergency fund, consider setting up a savings plan dedicated to unexpected expenses. This can also include exploring options for life insurance policies or personal finance strategies to protect your financial future and minimize the impact of unexpected expenses. 7. Invest In Index Funds Investing in index funds can be a smart way to build wealth in your 40s. Index funds are a type of mutual fund that tracks a specific index, such as the S&P 500, and provides a low-cost way to diversify your investment portfolio. One of the main benefits of investing in index funds is that they offer a high level of stability and consistency, making them an attractive option for risk-averse investors. Additionally, index funds typically have lower expense ratios compared to actively managed funds, which can result in higher returns for investors over the long term. With index funds, you can invest in a wide range of assets, including stocks, bonds, and real estate, which can provide you with greater exposure to different sectors and industries. Another advantage of index funds is their passive management style, which means that you don't need to constantly monitor and adjust your investments. This can be particularly beneficial for busy professionals in their 40s who don't have the time or expertise to actively manage their investment portfolios. However, it's important to note that investing in index funds still involves risk and requires careful consideration of your financial goals and risk tolerance. It's also important to regularly review and rebalance your portfolio to ensure that it aligns with your investment objectives. 8. Invest In A Skill Developing a new skill is one of the most effective ways to build wealth in your 40s. Whether it's learning a new language or taking courses to enhance your professional expertise, investing in yourself can lead to a higher salary, increased job security, and, ultimately, greater financial stability. By doing so, you can open up opportunities to expand your income sources, explore higher-paying job roles, or even start a small business on the side. With additional income, you can pay off mortgage payments or credit card debt, save for retirement, or even free money to invest in other areas of your financial plan. Moreover, upskilling also allows you to stay competitive in the job market and adapt to changing industry trends. This can lead to increased job security and the ability to negotiate a higher salary or better benefits. However, it's important to note that investing in a skill requires an investment - both time and money. You may need to take courses, attend conferences, or pay for specialized training. It's important to include these expenses in your planning and consider them as part of your retirement savings goals. Ultimately, learning a skill or improving on existing ones can be a wise financial decision that can pay off in the long run. By enhancing your knowledge and expertise, you can secure a brighter financial future and achieve greater personal and professional fulfillment. 9. Hire A Financial Advisor If You’re Earning Good Working with a financial advisor can also help you identify opportunities to save more money and optimize your investment portfolio. They can help you explore the world of financial planning, retirement plans, savings options, and various investment areas. Furthermore, an advisor can assist you in evaluating your financial situation and developing a long-term strategy that helps you achieve financial stability and security. Conclusion As you embark on your journey to building wealth in your 40s, it's important to remember that financial stability is within reach. By implementing the strategies we've discussed, including settling your mortgage early, being debt-free, expanding your income sources, building an emergency fund, and investing wisely, you can take control of your financial situation and achieve your retirement savings goals. Managing your living expenses and obtaining good health insurance are essential parts of building a secure financial future. By following these principles and seeking expert guidance as necessary, you can build a solid financial foundation that will serve you well throughout your life. Remember, building wealth takes time and patience, but with perseverance and smart decision-making, you can achieve financial stability and enjoy a prosperous future. <QUERY> What is the holistic approach to financial planning?

You may only respond to the prompt using the information in the context block. If you cannot answer based on the context block alone, say, "I am unable to answer that due to lack of context." Do not use more than 300 words in your response.

Summarize the argument for not holding companies to contracts signed before the pandemic but fulfilled during the pandemic.

THE ROLE OF CONTRACT LAW IN SUPPLY CHAINS Food supply chains are normally composed of vertical and horizontal chains of contracts connecting various core value-chain actors from producers to consumers, as well as contractual relations among operators of support services (e.g. purchase of inputs, financial agreements). All contracts in the chain should be fair and equitable for all parties and administered in good faith. The contracts should clarify the parties’ rights and responsibilities, paying attention to the essential elements of a contract as stipulated in the national contract law. Commonly, these essential elements would include, at least, the identification of the parties, offer and acceptance, obligations, price determination, remedies in case of partial or non-compliance, termination and provisions on dispute resolution, including alternative dispute resolution (ADR). In the context of a pandemic, the risk thatsome of these elements may be compromised is increased. Contracts should always ensure fair and equitable risk allocation and management. Certain risk allocation and management would – to some extent – be covered by the concepts of force majeure and/or change of circumstances, which are designed to respond to both natural disasters (disease outbreaks, disasters, etc.) and societal events (export bans, movement restrictions, etc.). Domestic legislation often requires four simultaneous conditions to be fulfilled before the application of force majeure: the event should be 1) unforeseeable, 2) unavoidable 3) outside the parties’ control and 4) it should objectively prevent one or both of them from performing. Change of circumstances (hardship-like situations) generally requires the first three pre-conditions. Such change in circumstances would not necessarily prevent parties from performing, but it would fundamentally change the basis on which the contract was formed and alter the balance of the relationship, making it unfair to hold either or both parties to their original obligations (UNIDROIT, FAO and IFAD, 2015). Parties who concluded a contract prior to the outbreak of COVID-19 and the subsequent imposition of related restrictions, may claim that either force majeure or change of circumstances, depending on the legal and factual context, apply to their ongoing contractual relationship. The final application of force majeure or change of circumstances would depend on a national court’s or an ADR mechanism’s interpretation of the applicable criteria and may excuse compliance with, or suspend, the affected obligations or lead to renegotiation of the contract. For contracts concluded after the declaration of the emergency, the application or not of these clauses would depend on whether further changes in circumstances, connected to the emergency, can be considered “unforeseeable”, months into the pandemic. This uncertainty needs to be taken into account by those who enter into new contracts under current conditions. The negotiation and drafting of new contracts should aim at providing clarity on what should happen to the contractual relationship due to the continuing and emerging impacts of COVID-19. Considerable contractual innovation, as supported and protected by the principle of freedom of contract, is required to ensure equitable risk allocation. One option could be to explicitly agree in the contract to consider COVID-19 and its related upheavals as force majeure, or change of circumstances, where the domestic legislation allows partiesto depart from the standard andmost probably narrowlegal definitions of these terms. Another option would be for the contract to mandate the parties to renegotiate the contract, either after some time has passed or if a certain event triggers the need to do so (such as new movement restrictions imposed by the government). Finally, the contracts could also explicitly consider COVID-19 and its effects when drafting remedies for contractual breaches, such as waiving the use of remedies or opting for less disruptive and more lenient options when the underlying breach was demonstrably caused by the pandemic. Unfortunately, contractual innovation may also open the door for the stronger party in a contract to take advantage and impose imbalancesin risk allocation between the parties through the introduction of unfair contractual terms and practices. A classic example of an unfair practice would be for the contract to allow only one party to unilaterally terminate the contract without notifying or discussing it in advance with the other party. On a general level, this requires governments to either adopt, or increase enforcement of, unfair contractual practices legislation to prohibit the use of contractual terms and practices that are considered unfair. Enhanced enforcement should begin immediately, as abuses may already be happening. At the same time, if there are gaps, the reform of the legislative framework should commence in earnest as it requires an investment of effort and time and will likely go beyond the duration of the current COVID-19 crisis. In the context of food supply chains, at least for nodessuch as contracts between smallholder producers and their buyers, governments may consider creating either mandatory or voluntary registries for contracts. These can increase transparency and legal certainty for parties, when they know that their contract (with sensitive commercial information removed) may be accessible to a defined audience (Viinikainen and Bullón, 2018). Greater prominence and application of the common, but not universally accepted, principle of good faith should be promoted in this time of uncertainty and can be effective if it is backed by the threat of enforcement. The principle of good faith requires the parties to interact honestly and fairly, and refrain from taking actions that would deny their counterparty from receiving the expected benefits of the contract. Essentially, good faith infuses the contract relationship with the kind of flexibility required to address the complications that come with a pandemic or any other global emergency. Good faith may involve applying, orrefraining from adopting, certain conduct (UNIDROIT, FAO and IFAD, 2015). In the context of COVID-19 this could include greater flexibility for delivery times, honest and timely exchange of information between the parties on the impacts that the emergency has had to better anticipate difficulties, as well as willingnessto renegotiate to better adjust the contractual relationship to the rapidly changing circumstances. Finally, as good contractual practice, it is important to include reference to grievance mechanisms in the contract. This is even more important in the uncertainty created by COVID19, which may increase the likelihood of both breaches and disputes. Deciding on the method of dispute resolution in advance is important as, once a dispute has arisen, it may be difficult for the parties to agree on how to resolve it. In general, for smallholders in particular, the use of ADR mechanisms, such as arbitration and mediation, may be preferable as they tend to be less costly, less formal and faster in dealing with disputes than the courts.

[Context Block] THE ROLE OF CONTRACT LAW IN SUPPLY CHAINS Food supply chains are normally composed of vertical and horizontal chains of contracts connecting various core value-chain actors from producers to consumers, as well as contractual relations among operators of support services (e.g. purchase of inputs, financial agreements). All contracts in the chain should be fair and equitable for all parties and administered in good faith. The contracts should clarify the parties’ rights and responsibilities, paying attention to the essential elements of a contract as stipulated in the national contract law. Commonly, these essential elements would include, at least, the identification of the parties, offer and acceptance, obligations, price determination, remedies in case of partial or non-compliance, termination and provisions on dispute resolution, including alternative dispute resolution (ADR). In the context of a pandemic, the risk thatsome of these elements may be compromised is increased. Contracts should always ensure fair and equitable risk allocation and management. Certain risk allocation and management would – to some extent – be covered by the concepts of force majeure and/or change of circumstances, which are designed to respond to both natural disasters (disease outbreaks, disasters, etc.) and societal events (export bans, movement restrictions, etc.). Domestic legislation often requires four simultaneous conditions to be fulfilled before the application of force majeure: the event should be 1) unforeseeable, 2) unavoidable 3) outside the parties’ control and 4) it should objectively prevent one or both of them from performing. Change of circumstances (hardship-like situations) generally requires the first three pre-conditions. Such change in circumstances would not necessarily prevent parties from performing, but it would fundamentally change the basis on which the contract was formed and alter the balance of the relationship, making it unfair to hold either or both parties to their original obligations (UNIDROIT, FAO and IFAD, 2015). Parties who concluded a contract prior to the outbreak of COVID-19 and the subsequent imposition of related restrictions, may claim that either force majeure or change of circumstances, depending on the legal and factual context, apply to their ongoing contractual relationship. The final application of force majeure or change of circumstances would depend on a national court’s or an ADR mechanism’s interpretation of the applicable criteria and may excuse compliance with, or suspend, the affected obligations or lead to renegotiation of the contract. For contracts concluded after the declaration of the emergency, the application or not of these clauses would depend on whether further changes in circumstances, connected to the emergency, can be considered “unforeseeable”, months into the pandemic. This uncertainty needs to be taken into account by those who enter into new contracts under current conditions. The negotiation and drafting of new contracts should aim at providing clarity on what should happen to the contractual relationship due to the continuing and emerging impacts of COVID-19. Considerable contractual innovation, as supported and protected by the principle of freedom of contract, is required to ensure equitable risk allocation. One option could be to explicitly agree in the contract to consider COVID-19 and its related upheavals as force majeure, or change of circumstances, where the domestic legislation allows partiesto depart from the standard andmost probably narrowlegal definitions of these terms. Another option would be for the contract to mandate the parties to renegotiate the contract, either after some time has passed or if a certain event triggers the need to do so (such as new movement restrictions imposed by the government). Finally, the contracts could also explicitly consider COVID-19 and its effects when drafting remedies for contractual breaches, such as waiving the use of remedies or opting for less disruptive and more lenient options when the underlying breach was demonstrably caused by the pandemic. Unfortunately, contractual innovation may also open the door for the stronger party in a contract to take advantage and impose imbalancesin risk allocation between the parties through the introduction of unfair contractual terms and practices. A classic example of an unfair practice would be for the contract to allow only one party to unilaterally terminate the contract without notifying or discussing it in advance with the other party. On a general level, this requires governments to either adopt, or increase enforcement of, unfair contractual practices legislation to prohibit the use of contractual terms and practices that are considered unfair. Enhanced enforcement should begin immediately, as abuses may already be happening. At the same time, if there are gaps, the reform of the legislative framework should commence in earnest as it requires an investment of effort and time and will likely go beyond the duration of the current COVID-19 crisis. In the context of food supply chains, at least for nodessuch as contracts between smallholder producers and their buyers, governments may consider creating either mandatory or voluntary registries for contracts. These can increase transparency and legal certainty for parties, when they know that their contract (with sensitive commercial information removed) may be accessible to a defined audience (Viinikainen and Bullón, 2018). Greater prominence and application of the common, but not universally accepted, principle of good faith should be promoted in this time of uncertainty and can be effective if it is backed by the threat of enforcement. The principle of good faith requires the parties to interact honestly and fairly, and refrain from taking actions that would deny their counterparty from receiving the expected benefits of the contract. Essentially, good faith infuses the contract relationship with the kind of flexibility required to address the complications that come with a pandemic or any other global emergency. Good faith may involve applying, orrefraining from adopting, certain conduct (UNIDROIT, FAO and IFAD, 2015). In the context of COVID-19 this could include greater flexibility for delivery times, honest and timely exchange of information between the parties on the impacts that the emergency has had to better anticipate difficulties, as well as willingnessto renegotiate to better adjust the contractual relationship to the rapidly changing circumstances. Finally, as good contractual practice, it is important to include reference to grievance mechanisms in the contract. This is even more important in the uncertainty created by COVID19, which may increase the likelihood of both breaches and disputes. Deciding on the method of dispute resolution in advance is important as, once a dispute has arisen, it may be difficult for the parties to agree on how to resolve it. In general, for smallholders in particular, the use of ADR mechanisms, such as arbitration and mediation, may be preferable as they tend to be less costly, less formal and faster in dealing with disputes than the courts. [System Instruction] You may only respond to the prompt using the information in the context block. If you cannot answer based on the context block alone, say, "I am unable to answer that due to lack of context." Do not use more than 300 words in your response. [Question] Summarize the argument for not holding companies to contracts signed before the pandemic but fulfilled during the pandemic.

The document should be the only source used to answer the question.

Does chewing gum cause tooth decay?

**Oral Effects of Chewing Gum** Chewing gum after a meal can increase salivary flow by stimulating both mechanical and taste receptors in the mouth. The average unstimulated salivary flow rate for healthy people is 0.3-0.4 mL/min.6 The physical act of chewing stimulates salivary flow: simply chewing unsweetened, unflavored chewing gum base stimulates the salivary flow rate by 10-12 times that of the unstimulated rate.7 Flavors also act as salivary stimulants.6 The stimulated salivary flow rate is significantly greater while chewing sweetened and flavored gum as opposed to unsweetened, unflavored chewing gum base.7, 8 Increasing saliva volume helps to dilute and neutralize acids produced by the bacteria in plaque on teeth. Over time, these acids can damage tooth enamel, potentially resulting in decay. There are several mechanisms by which stimulated saliva flow may protect against dental caries. Increased saliva flow carries with it calcium and phosphate ions, which can contribute to remineralization of tooth enamel; the presence of fluoride in the saliva can serve to replace enamel components magnesium and carbonate with the stronger, more caries-resistant fluorapatite crystals.9 Saliva can buffer the effects of acids in foods or drinks that could otherwise soften teeth’s enamel surface, and swallowing excess saliva created by stimulation clears acid.8 While unstimulated saliva does not have a strong buffering capacity against acid, stimulated saliva has higher concentrations of protein, sodium, calcium, chloride, and bicarbonate increasing its buffering capacity.6 Additionally, saliva contributes proteins to dental surfaces, creating an acquired enamel pellicle that protects against dental erosion.6, 8 Sugar-containing Chewing Gum Monosaccharides and disaccharides may be used in sugar-containing chewing gum. These fermentable carbohydrates can be metabolized by oral bacteria. The bacteria (particularly S. mutans and Lactobacillus spp.) in turn produce dental biofilm and acid, which can lead to enamel demineralization and caries.10 The potential cariogenicity of sugar-containing gum depends on the physical consistency, oral retention time of the gum, the frequency with which it is chewed, and the sequence of consumption (for instance, chewing sugar-containing gum before eating foods that reduce acid production will be less cariogenic than the reverse).10 Sugar-free Chewing Gum As defined by the Food and Drug Administration (FDA) in the Code of Federal Regulations (CFR) a food or food substance such as chewing gum, can be labeled as “sugar-free” if it contains less than 0.5 g of sugars per serving.11 In place of sugar, these gums use high-intensity sweeteners such as aspartame, acesulfame-K, neotame, saccharin, sucralose or stevia.12 They also may be sweetened with sugar alcohols such as erythritol, isomalt, maltitol, mannitol, sorbitol, or xylitol.12 These high-intensity sweeteners, with the exception of aspartame, are considered non-nutritive and contain fewer calories than sugar, but the FDA categorizes aspartame, as well as the aforementioned sugar alcohols, to be nutritive sweeteners, since they contain more than 2% of the calories in an equivalent amount of sugar.13 Clinical trials have found decreased caries incidence in subjects who chewed sugar-free gum for 20 minutes after meals.14, 15 Unlike sugar, these sweeteners are noncariogenic, since they are metabolized slowly or not at all by cariogenic plaque bacteria.16 A 2021 systematic review and meta-analysis by Nasseripour et al.17 examined the use of sugar-free gum sweetened with xylitol and reported that the use of sugar-free chewing gum resulted in a statistically significant reduction in the S. mutans load. The authors reported an effect size of -0.42 (95% CI: -0.60 to -0.25), which is suggestive of its benefit as an adjunct to recommended home oral hygiene.

{QUERY} ========== Does chewing gum cause tooth decay? {SYSTEM INSTRUCTION} ========== The document should be the only source used to answer the question. {PASSAGE} ========== **Oral Effects of Chewing Gum** Chewing gum after a meal can increase salivary flow by stimulating both mechanical and taste receptors in the mouth. The average unstimulated salivary flow rate for healthy people is 0.3-0.4 mL/min.6 The physical act of chewing stimulates salivary flow: simply chewing unsweetened, unflavored chewing gum base stimulates the salivary flow rate by 10-12 times that of the unstimulated rate.7 Flavors also act as salivary stimulants.6 The stimulated salivary flow rate is significantly greater while chewing sweetened and flavored gum as opposed to unsweetened, unflavored chewing gum base.7, 8 Increasing saliva volume helps to dilute and neutralize acids produced by the bacteria in plaque on teeth. Over time, these acids can damage tooth enamel, potentially resulting in decay. There are several mechanisms by which stimulated saliva flow may protect against dental caries. Increased saliva flow carries with it calcium and phosphate ions, which can contribute to remineralization of tooth enamel; the presence of fluoride in the saliva can serve to replace enamel components magnesium and carbonate with the stronger, more caries-resistant fluorapatite crystals.9 Saliva can buffer the effects of acids in foods or drinks that could otherwise soften teeth’s enamel surface, and swallowing excess saliva created by stimulation clears acid.8 While unstimulated saliva does not have a strong buffering capacity against acid, stimulated saliva has higher concentrations of protein, sodium, calcium, chloride, and bicarbonate increasing its buffering capacity.6 Additionally, saliva contributes proteins to dental surfaces, creating an acquired enamel pellicle that protects against dental erosion.6, 8 Sugar-containing Chewing Gum Monosaccharides and disaccharides may be used in sugar-containing chewing gum. These fermentable carbohydrates can be metabolized by oral bacteria. The bacteria (particularly S. mutans and Lactobacillus spp.) in turn produce dental biofilm and acid, which can lead to enamel demineralization and caries.10 The potential cariogenicity of sugar-containing gum depends on the physical consistency, oral retention time of the gum, the frequency with which it is chewed, and the sequence of consumption (for instance, chewing sugar-containing gum before eating foods that reduce acid production will be less cariogenic than the reverse).10 Sugar-free Chewing Gum As defined by the Food and Drug Administration (FDA) in the Code of Federal Regulations (CFR) a food or food substance such as chewing gum, can be labeled as “sugar-free” if it contains less than 0.5 g of sugars per serving.11 In place of sugar, these gums use high-intensity sweeteners such as aspartame, acesulfame-K, neotame, saccharin, sucralose or stevia.12 They also may be sweetened with sugar alcohols such as erythritol, isomalt, maltitol, mannitol, sorbitol, or xylitol.12 These high-intensity sweeteners, with the exception of aspartame, are considered non-nutritive and contain fewer calories than sugar, but the FDA categorizes aspartame, as well as the aforementioned sugar alcohols, to be nutritive sweeteners, since they contain more than 2% of the calories in an equivalent amount of sugar.13 Clinical trials have found decreased caries incidence in subjects who chewed sugar-free gum for 20 minutes after meals.14, 15 Unlike sugar, these sweeteners are noncariogenic, since they are metabolized slowly or not at all by cariogenic plaque bacteria.16 A 2021 systematic review and meta-analysis by Nasseripour et al.17 examined the use of sugar-free gum sweetened with xylitol and reported that the use of sugar-free chewing gum resulted in a statistically significant reduction in the S. mutans load. The authors reported an effect size of -0.42 (95% CI: -0.60 to -0.25), which is suggestive of its benefit as an adjunct to recommended home oral hygiene.

Only use the provided text in the prompt to answer questions. Do not use external knowledge.

How does hypermobile EDS compare to classic EDS?

Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications. The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were identified more recently. The 2017 classification describes 13 types of Ehlers- Danlos syndrome. An unusually large range of joint movement (hypermobility) occurs in most forms of Ehlers-Danlos syndrome, and it is a hallmark feature of the hypermobile type. Infants and children with hypermobility often have weak muscle tone (hypotonia), which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. In the arthrochalasia type of Ehlers-Danlos syndrome, infants have hypermobility and dislocations of both hips at birth. Many people with the Ehlers-Danlos syndromes have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers- Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic "cigarette paper" scars. The dermatosparaxis type of the disorder is characterized by loose skin that sags and wrinkles, and extra (redundant) folds of skin may be present. Bleeding problems are common in the vascular type of Ehlers-Danlos syndrome and are caused by unpredictable tearing (rupture) of blood vessels and organs. These complications can lead to easy bruising, internal bleeding, a hole in the wall of the intestine (intestinal perforation), or stroke. During pregnancy, women with vascular Ehlers-Danlos syndrome may experience rupture of the uterus. Additional forms of Ehlers-Danlos syndrome that involve rupture of the blood vessels include the kyphoscoliotic, classical, and classical-like types. Other types of Ehlers-Danlos syndrome have additional signs and symptoms. The cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart. People with the kyphoscoliotic type experience severe curvature of the spine that worsens over time and can interfere with breathing by restricting lung expansion. A type of Ehlers-Danlos syndrome called brittle cornea syndrome is characterized by thinness of the clear covering of the eye (the cornea) and other eye abnormalities. The spondylodysplastic type features short stature and skeletal abnormalities such as abnormally curved (bowed) limbs. Abnormalities of muscles, including hypotonia and permanently bent joints (contractures), are among the characteristic signs of the musculocontractural and myopathic forms of Ehlers-Danlos syndrome. The periodontal type causes abnormalities of the teeth and gums. Frequency The combined prevalence of all types of Ehlers-Danlos syndrome appears to be at least 1 in 5,000 individuals worldwide. The hypermobile and classical forms are most common; the hypermobile type may affect as many as 1 in 5,000 to 20,000 people, while the classical type probably occurs in 1 in 20,000 to 40,000 people. Other forms of Ehlers-Danlos syndrome are rare, often with only a few cases or affected families described in the medical literature.Variants (also known as mutations) in at least 20 genes have been found to cause the Ehlers-Danlos syndromes. Variants in the COL5A1 or COL5A2 gene, or rarely in the COL1A1 gene, can cause the classical type. Variants in the TNXB gene cause the classical-like type and have been reported in a very small percentage of cases of the hypermobile type (although in most people with this type, the cause is unknown). The cardiac-valvular type and some cases of the arthrochalasia type are caused by COL1A2 gene variants; variants in the COL1A1 gene have also been found in people with the arthrochalasia type. Most cases of the vascular type result from variants in the COL3A1 gene, although rarely this type is caused by certain COL1A1 gene variants. The dermatosparaxis type is caused by variants in the ADAMTS2 gene. PLOD1 or FKBP14 gene variants result in the kyphoscoliotic type. Other rare forms of Ehlers-Danlos syndrome result from variants in other genes. Some of the genes associated with the Ehlers-Danlos syndromes, including COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2, provide instructions for making pieces of several different types of collagen. These pieces assemble to form mature collagen molecules that give structure and strength to connective tissues throughout the body. Other genes, including ADAMTS2, FKBP14, PLOD1, and TNXB, provide instructions for making proteins that process, fold, or interact with collagen. Variants in any of these genes disrupt the production or processing of collagen, preventing these molecules from being assembled properly. These changes weaken connective tissues in the skin, bones, and other parts of the body, resulting in the characteristic features of the Ehlers- Danlos syndromes.

system instruction: [Only use the provided text in the prompt to answer questions. Do not use external knowledge.] question: [How does hypermobile EDS compare to classic EDS?] context block: [Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications. The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were identified more recently. The 2017 classification describes 13 types of Ehlers- Danlos syndrome. An unusually large range of joint movement (hypermobility) occurs in most forms of Ehlers-Danlos syndrome, and it is a hallmark feature of the hypermobile type. Infants and children with hypermobility often have weak muscle tone (hypotonia), which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. In the arthrochalasia type of Ehlers-Danlos syndrome, infants have hypermobility and dislocations of both hips at birth. Many people with the Ehlers-Danlos syndromes have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers- Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic "cigarette paper" scars. The dermatosparaxis type of the disorder is characterized by loose skin that sags and wrinkles, and extra (redundant) folds of skin may be present. Bleeding problems are common in the vascular type of Ehlers-Danlos syndrome and are caused by unpredictable tearing (rupture) of blood vessels and organs. These complications can lead to easy bruising, internal bleeding, a hole in the wall of the intestine (intestinal perforation), or stroke. During pregnancy, women with vascular Ehlers-Danlos syndrome may experience rupture of the uterus. Additional forms of Ehlers-Danlos syndrome that involve rupture of the blood vessels include the kyphoscoliotic, classical, and classical-like types. Other types of Ehlers-Danlos syndrome have additional signs and symptoms. The cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart. People with the kyphoscoliotic type experience severe curvature of the spine that worsens over time and can interfere with breathing by restricting lung expansion. A type of Ehlers-Danlos syndrome called brittle cornea syndrome is characterized by thinness of the clear covering of the eye (the cornea) and other eye abnormalities. The spondylodysplastic type features short stature and skeletal abnormalities such as abnormally curved (bowed) limbs. Abnormalities of muscles, including hypotonia and permanently bent joints (contractures), are among the characteristic signs of the musculocontractural and myopathic forms of Ehlers-Danlos syndrome. The periodontal type causes abnormalities of the teeth and gums. Frequency The combined prevalence of all types of Ehlers-Danlos syndrome appears to be at least 1 in 5,000 individuals worldwide. The hypermobile and classical forms are most common; the hypermobile type may affect as many as 1 in 5,000 to 20,000 people, while the classical type probably occurs in 1 in 20,000 to 40,000 people. Other forms of Ehlers-Danlos syndrome are rare, often with only a few cases or affected families described in the medical literature.Variants (also known as mutations) in at least 20 genes have been found to cause the Ehlers-Danlos syndromes. Variants in the COL5A1 or COL5A2 gene, or rarely in the COL1A1 gene, can cause the classical type. Variants in the TNXB gene cause the classical-like type and have been reported in a very small percentage of cases of the hypermobile type (although in most people with this type, the cause is unknown). The cardiac-valvular type and some cases of the arthrochalasia type are caused by COL1A2 gene variants; variants in the COL1A1 gene have also been found in people with the arthrochalasia type. Most cases of the vascular type result from variants in the COL3A1 gene, although rarely this type is caused by certain COL1A1 gene variants. The dermatosparaxis type is caused by variants in the ADAMTS2 gene. PLOD1 or FKBP14 gene variants result in the kyphoscoliotic type. Other rare forms of Ehlers-Danlos syndrome result from variants in other genes. Some of the genes associated with the Ehlers-Danlos syndromes, including COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2, provide instructions for making pieces of several different types of collagen. These pieces assemble to form mature collagen molecules that give structure and strength to connective tissues throughout the body. Other genes, including ADAMTS2, FKBP14, PLOD1, and TNXB, provide instructions for making proteins that process, fold, or interact with collagen. Variants in any of these genes disrupt the production or processing of collagen, preventing these molecules from being assembled properly. These changes weaken connective tissues in the skin, bones, and other parts of the body, resulting in the characteristic features of the Ehlers- Danlos syndromes.]

Answer only using the information in the provided context and limit your answer to 200 words.

Why is it important for patients with chronic illnesses to engage with their own care?

2.1.1. Importance of social networks, family support, and peer relationships in chronic disease management Social networks, family support, and peer relationships play a vital role in the effective management of chronic diseases. These forms of support provide emotional, practical, and informational assistance, which are crucial for helping individuals navigate the complexities of their conditions [23]. Family support, for instance, can offer direct help with daily tasks, medication management, and encouragement to adhere to treatment plans, thereby reducing the patient's stress and burden. Strong social networks, including friends and community connections, contribute to a sense of belonging and emotional well-being, which can buffer against the psychological challenges of chronic illness. Peer relationships, such as those found in support groups, provide opportunities for individuals to share experiences, exchange coping strategies, and receive empathy and understanding from others facing similar challenges. These interactions can enhance motivation, reduce feelings of isolation, and improve overall mental health. By leveraging these social resources, patients with chronic diseases are better equipped to manage their health, adhere to treatment regimens, and maintain a higher quality of life [24]. 2.1.2. Impact of social isolation and loneliness on treatment adherence and health-related behaviors Social isolation and loneliness have profound negative impacts on treatment adherence and health-related behaviors in individuals with chronic diseases. When patients feel isolated, they often experience higher levels of stress, anxiety, and depression, which can diminish their motivation to follow treatment regimens and engage in self-care activities. The absence of a supportive social network means there is no one to remind or encourage them to take their medications, attend medical appointments, or maintain healthy lifestyle practices such as regular exercise and proper nutrition [25]. Loneliness can also lead to unhealthy behaviors, such as poor diet, lack of physical activity, and increased substance use, further exacerbating the patient's condition. Furthermore, isolated individuals may lack access to crucial health information and resources that could aid in their disease management. Consequently, social isolation and loneliness not only hinder effective disease management but also contribute to a decline in overall physical and mental health, highlighting the importance of fostering social connections and support systems for individuals with chronic illnesses [26] 2.2. Coping Strategies and Resilience Effective coping strategies are essential for managing chronic illness. Adaptive coping mechanisms, such as problemfocused coping, which involves tackling the problem directly, and emotion-focused coping, which aims to manage emotional responses, can help patients better manage the challenges of chronic disease [27]. These strategies can mitigate the adverse effects of stress and improve overall quality of life. Resilience factors, such as optimism, selfefficacy, and the ability to find meaning in the face of illness, play a significant role in enhancing a patient's ability to cope with chronic conditions. Resilient individuals are more likely to maintain a positive outlook, adhere to treatment regimens, and engage in proactive health behaviors, all of which contribute to better health outcomes and improved quality of life [28]. 2.2.1. Adaptive coping mechanisms Adaptive coping mechanisms play a critical role in managing chronic illness by helping individuals navigate the emotional and practical challenges associated with their condition. Problem-focused coping involves actively addressing the issues causing stress, such as developing a structured treatment plan, seeking information about the illness, or finding solutions to daily obstacles related to the condition [29][30]. This approach empowers patients to take control of their health by directly tackling the problems at hand. Emotion-focused coping, on the other hand, helps individuals manage the emotional responses to their illness. Techniques such as relaxation exercises, mindfulness, and seeking emotional support from friends and family can reduce feelings of anxiety, depression, and frustration. By employing these adaptive coping strategies, patients can mitigate the adverse effects of stress, improve their psychological well-being, and enhance their ability to adhere to treatment plans. Ultimately, these coping mechanisms contribute to a better quality of life and more effective management of chronic illness [31]. 2.2.2. Resilience factors and their role in mitigating stress and enhancing quality of life Resilience factors, such as optimism, self-efficacy, and a strong sense of purpose, play a crucial role in mitigating stress and enhancing the quality of life for individuals managing chronic illness. Optimism helps patients maintain a positive outlook despite their challenges, fostering hope and a belief in positive outcomes [32]. This positive mindset can buffer the impact of stress and encourage proactive health behaviors. Self-efficacy, or the belief in one's ability to manage and control life events, empowers patients to take charge of their treatment and make informed decisions about their health. A strong sense of purpose provides motivation and direction, helping patients find meaning and value in their experiences, which can be particularly important in coping with long-term health issues. These resilience factors collectively reduce the psychological burden of chronic illness, promote better adherence to treatment regimens, and enhance overall well-being, leading to an improved quality of life. By fostering resilience, healthcare providers can help patients build the mental and emotional strength needed to navigate the complexities of chronic disease management [33][34]. 3. Health Beliefs and Patient Engagement Health beliefs, including perceptions of illness and beliefs about treatment efficacy, significantly influence patient behaviors and engagement in self-care. Patients who believe their condition is manageable and that their treatment plan is effective are more likely to adhere to medical advice and participate actively in their care[26]. Conversely, negative health beliefs can lead to disengagement and poor adherence to treatment regimens. Strategies to promote patient engagement include education about the disease and its management, motivational interviewing to build confidence and commitment, and creating a collaborative care environment where patients feel empowered to take an active role in their health. By fostering positive health beliefs and encouraging active participation, healthcare providers can improve treatment adherence and health outcomes [28]. 3.1. Influence of health beliefs, perceptions of illness, and treatment efficacy on patient behaviors Health beliefs, perceptions of illness, and views on treatment efficacy significantly influence patient behaviors and their approach to managing chronic disease. Patients' beliefs about their health, including how they perceive their illness and its severity, can determine their willingness to adhere to treatment plans and engage in self-care activities [35][36]. For instance, if a patient believes that their condition is manageable and that the prescribed treatment is effective, they are more likely to follow medical advice, take medications as directed, and make necessary lifestyle changes. Conversely, if a patient perceives their illness as overwhelming or doubts the efficacy of the treatment, they may be less motivated to adhere to their treatment regimen, potentially leading to poorer health outcomes. These health beliefs also affect psychological responses to illness; patients with a positive outlook are more likely to experience lower levels of stress and anxiety, further promoting better health behaviors. Understanding and addressing these beliefs through patient education and motivational interviewing can help healthcare providers enhance patient engagement, encourage active participation in care, and ultimately improve health outcomes [37]. 3.2. Strategies for promoting patient engagement and active participation in self-care Promoting patient engagement and active participation in self-care involves implementing strategies that empower patients and enhance their motivation to manage their health effectively. One key approach is patient education, which provides individuals with comprehensive information about their condition, treatment options, and the importance of adherence to medical advice. This education can be delivered through various mediums such as brochures, workshops, or digital platforms [39]. Motivational interviewing is another effective technique, where healthcare providers engage in open-ended discussions to explore patients' beliefs and barriers, helping them set achievable goals and find intrinsic motivation for self-care. Building a collaborative care environment is also crucial, where patients are encouraged to take an active role in decision-making processes regarding their treatment plans. Additionally, providing tools and resources, such as self-monitoring apps and support groups, can facilitate self-management by offering continuous support and tracking progress. By creating a supportive and informative environment, healthcare providers can foster greater patient engagement, leading to improved adherence to treatment regimens and better health outcomes [40].

2.1.1. Importance of social networks, family support, and peer relationships in chronic disease management Social networks, family support, and peer relationships play a vital role in the effective management of chronic diseases. These forms of support provide emotional, practical, and informational assistance, which are crucial for helping individuals navigate the complexities of their conditions [23]. Family support, for instance, can offer direct help with daily tasks, medication management, and encouragement to adhere to treatment plans, thereby reducing the patient's stress and burden. Strong social networks, including friends and community connections, contribute to a sense of belonging and emotional well-being, which can buffer against the psychological challenges of chronic illness. Peer relationships, such as those found in support groups, provide opportunities for individuals to share experiences, exchange coping strategies, and receive empathy and understanding from others facing similar challenges. These interactions can enhance motivation, reduce feelings of isolation, and improve overall mental health. By leveraging these social resources, patients with chronic diseases are better equipped to manage their health, adhere to treatment regimens, and maintain a higher quality of life [24]. 2.1.2. Impact of social isolation and loneliness on treatment adherence and health-related behaviors Social isolation and loneliness have profound negative impacts on treatment adherence and health-related behaviors in individuals with chronic diseases. When patients feel isolated, they often experience higher levels of stress, anxiety, and depression, which can diminish their motivation to follow treatment regimens and engage in self-care activities. The absence of a supportive social network means there is no one to remind or encourage them to take their medications, attend medical appointments, or maintain healthy lifestyle practices such as regular exercise and proper nutrition [25]. Loneliness can also lead to unhealthy behaviors, such as poor diet, lack of physical activity, and increased substance use, further exacerbating the patient's condition. Furthermore, isolated individuals may lack access to crucial health information and resources that could aid in their disease management. Consequently, social isolation and loneliness not only hinder effective disease management but also contribute to a decline in overall physical and mental health, highlighting the importance of fostering social connections and support systems for individuals with chronic illnesses [26] 2.2. Coping Strategies and Resilience Effective coping strategies are essential for managing chronic illness. Adaptive coping mechanisms, such as problemfocused coping, which involves tackling the problem directly, and emotion-focused coping, which aims to manage emotional responses, can help patients better manage the challenges of chronic disease [27]. These strategies can mitigate the adverse effects of stress and improve overall quality of life. Resilience factors, such as optimism, selfefficacy, and the ability to find meaning in the face of illness, play a significant role in enhancing a patient's ability to cope with chronic conditions. Resilient individuals are more likely to maintain a positive outlook, adhere to treatment regimens, and engage in proactive health behaviors, all of which contribute to better health outcomes and improved quality of life [28]. 2.2.1. Adaptive coping mechanisms Adaptive coping mechanisms play a critical role in managing chronic illness by helping individuals navigate the emotional and practical challenges associated with their condition. Problem-focused coping involves actively addressing the issues causing stress, such as developing a structured treatment plan, seeking information about the illness, or finding solutions to daily obstacles related to the condition [29][30]. This approach empowers patients to take control of their health by directly tackling the problems at hand. Emotion-focused coping, on the other hand, helps individuals manage the emotional responses to their illness. Techniques such as relaxation exercises, mindfulness, and seeking emotional support from friends and family can reduce feelings of anxiety, depression, and frustration. By employing these adaptive coping strategies, patients can mitigate the adverse effects of stress, improve their psychological well-being, and enhance their ability to adhere to treatment plans. Ultimately, these coping mechanisms contribute to a better quality of life and more effective management of chronic illness [31]. 2.2.2. Resilience factors and their role in mitigating stress and enhancing quality of life Resilience factors, such as optimism, self-efficacy, and a strong sense of purpose, play a crucial role in mitigating stress and enhancing the quality of life for individuals managing chronic illness. Optimism helps patients maintain a positive outlook despite their challenges, fostering hope and a belief in positive outcomes [32]. This positive mindset can buffer the impact of stress and encourage proactive health behaviors. Self-efficacy, or the belief in one's ability to manage and control life events, empowers patients to take charge of their treatment and make informed decisions about their health. A strong sense of purpose provides motivation and direction, helping patients find meaning and value in their experiences, which can be particularly important in coping with long-term health issues. These resilience factors collectively reduce the psychological burden of chronic illness, promote better adherence to treatment regimens, and enhance overall well-being, leading to an improved quality of life. By fostering resilience, healthcare providers can help patients build the mental and emotional strength needed to navigate the complexities of chronic disease management [33][34]. 3. Health Beliefs and Patient Engagement Health beliefs, including perceptions of illness and beliefs about treatment efficacy, significantly influence patient behaviors and engagement in self-care. Patients who believe their condition is manageable and that their treatment plan is effective are more likely to adhere to medical advice and participate actively in their care[26]. Conversely, negative health beliefs can lead to disengagement and poor adherence to treatment regimens. Strategies to promote patient engagement include education about the disease and its management, motivational interviewing to build confidence and commitment, and creating a collaborative care environment where patients feel empowered to take an active role in their health. By fostering positive health beliefs and encouraging active participation, healthcare providers can improve treatment adherence and health outcomes [28]. 3.1. Influence of health beliefs, perceptions of illness, and treatment efficacy on patient behaviors Health beliefs, perceptions of illness, and views on treatment efficacy significantly influence patient behaviors and their approach to managing chronic disease. Patients' beliefs about their health, including how they perceive their illness and its severity, can determine their willingness to adhere to treatment plans and engage in self-care activities [35][36]. For instance, if a patient believes that their condition is manageable and that the prescribed treatment is effective, they are more likely to follow medical advice, take medications as directed, and make necessary lifestyle changes. Conversely, if a patient perceives their illness as overwhelming or doubts the efficacy of the treatment, they may be less motivated to adhere to their treatment regimen, potentially leading to poorer health outcomes. These health beliefs also affect psychological responses to illness; patients with a positive outlook are more likely to experience lower levels of stress and anxiety, further promoting better health behaviors. Understanding and addressing these beliefs through patient education and motivational interviewing can help healthcare providers enhance patient engagement, encourage active participation in care, and ultimately improve health outcomes [37]. 3.2. Strategies for promoting patient engagement and active participation in self-care Promoting patient engagement and active participation in self-care involves implementing strategies that empower patients and enhance their motivation to manage their health effectively. One key approach is patient education, which provides individuals with comprehensive information about their condition, treatment options, and the importance of adherence to medical advice. This education can be delivered through various mediums such as brochures, workshops, or digital platforms [39]. Motivational interviewing is another effective technique, where healthcare providers engage in open-ended discussions to explore patients' beliefs and barriers, helping them set achievable goals and find intrinsic motivation for self-care. Building a collaborative care environment is also crucial, where patients are encouraged to take an active role in decision-making processes regarding their treatment plans. Additionally, providing tools and resources, such as self-monitoring apps and support groups, can facilitate self-management by offering continuous support and tracking progress. By creating a supportive and informative environment, healthcare providers can foster greater patient engagement, leading to improved adherence to treatment regimens and better health outcomes [40]. Why is it important for patients with chronic illnesses to engage with their own care? Answer only using the information in the provided context and limit your answer to 200 words.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

I would like to understand the differences between traditional and self-publishing. How do I know which route to go? Which route has the potential for a greater profit?

Your two main options are traditional publishing with a publishing company, or self-publishing through a platform like IngramSpark, Amazon Kindle Direct, or Indie Author Project / Biblioboard. Many authors have strong opinions about which publishing path is best. Traditional publishing offers support from a full team of experts, including editors, designers, and salespeople, often leading to higher sales and a more polished product. However, traditional publishing is notoriously slow and has historically excluded writers from marginalized groups. Self-publishing offers a quicker way to share your book with readers, as well as freedom from industry pressure to write something “sellable.” However, self-published books can suffer from the lack of professional editing and design, and self-published authors take on the hard work of sales, marketing, and distribution. There’s no one right answer. It depends on your personal goals for writing and publication. Below are three questions to help you decide whether traditional publishing or self-publishing is right for you. You want to spend it writing, of course! However, writing is only one part of an author’s career. Authors also spend time revising, marketing their books, and, if you’re pursuing traditional publishing, finding an agent. Most major publishers do not accept submissions directly from writers. Instead, writers find agents who sell their work to publishers in return for around 15% of profits. Having an agent signals to publishers that your book is good enough for at least one person to stake their career on it. And having an agent means you can focus on writing your next book instead of researching every editor at every imprint of every publishing house, and then becoming an expert in negotiating your own publishing contract. However, you will have to put that research and negotiation power toward querying agents. During the querying process, writers email a brief pitch of their work to agents who may be interested. Querying is often considered one of the most difficult parts of traditional publishing, as writers may receive hundreds of rejections over multiple books. Rejection isn’t always bad, though. It can be an invitation to revise and improve your work. Writing is hard, and no one gets it right on the first try. Early drafts of a book get the idea out of your brain and into words. Later drafts make the story reach its full potential. Traditional publishing has multiple rounds of agent and editor revisions baked into the process. Self-publishing does not. Self-published writers decide for themselves how much to revise their work before sharing it. Some self-published authors hire freelance editors. Some trust friends and family for feedback. Others skip revisions, share the work as-is, and move on to their next project. Skipping revisions can have negative impacts on book quality, but ultimately, it’s a question of whether you’d prefer to spend your time telling new stories or polishing old ones. Before publication, it may seem like traditional publishing takes a lot more work than self-publishing. However, once a book is published, the tables turn. Traditional publishing includes whole teams of people working behind the scenes to determine how much books should cost, negotiate deals with booksellers, review books so teachers and librarians know which ones to buy, and more. If you’re self-publishing, you are those teams of people. You do all the work of pricing, formatting, selling, marketing, distributing, and more. Even if you only want to e-publish, you still have to format your own manuscript, or hire a professional to do it for you, and submit to the online platform(s) of your choice. You have to figure out a marketing strategy that will make you stand out, not only among self-published or indie authors, but also against professional marketing teams from billion-dollar publishing companies. It’s hard work! And it takes time away from writing. Whether you choose traditional or self-publishing, writing is only one aspect of your career. It’s worth asking whether you’d prefer to spend time querying agents or becoming an expert in everything from typesetting to book distribution. It’s also worth considering why you want a writing career in the first place. Every writer has their own reasons for writing. We love it. We don’t know how to live without it. We want to tell our story or make the world a better place. Usually, the answer is not money. And that’s okay! Creative expression can be fun and freeing and deeply meaningful, even if you never monetize it. If you know up front—before sending 100 query letters or spending hours and hours typesetting your manuscript—that writing is not a financial or career goal, you can save yourself a lot of stress and rejection. However, if you do want to make writing a financially viable career, it’s important to know how and when you get paid through traditional or self-publishing. In traditional publishing, when your agent sells your book to a publisher, you are paid an advance. An advance is a lump sum that the company expects to earn back later through your book sales. Advances vary wildly in amount. Small, indie publishers might pay as low as $1,000-$2,000. Large publishers might offer up to six figures or more. The amount depends on factors like genre, target age group, and whether it’s your first book or you’re more advanced in your career. After your book earns out its advance—meaning the publisher made back the money they paid you—then you earn royalties on every additional copy sold. In traditional publishing, writers do not pay anything up front. If your agent or editor charges “reading fees,” or if you are asked to pay for any part of book design or production, you are being scammed. This is an important distinction because self-publishing works differently. In self-publishing, your income depends entirely on how many books you sell. There are no advances. You may also have to pay up-front, depending on which parts of book production you want to tackle yourself and which parts (if any) you’d like to hire experts to manage for you. Up-front self-publishing costs could include hiring a freelance editor or book designer, or paying to print your book if you plan to sell hard copies. There are free e-publishing options, such as Kindle Direct or Indie Author Project / Biblioboard. For hard copies, a print-on-demand model like IngramSpark can save you from paying to print and warehouse extra books that you’re unable to sell. It can be difficult to know whether it’s financially better to shop around your manuscript a little longer, waiting for that big advance, or whether you should go ahead and self-publish to start selling copies now. The answer can depend on what genre you’re writing in and what age group you’re writing for. Your book’s length and genre, as well as the age of your readers, can have a huge impact on whether you’re able to make money in traditional or self-publishing. Sometimes, both can be profitable. Romance is a rare genre that both tops traditional publishing sales and has recently seen significant income growth for self-published authors. In fact, many romance writers are now “hybrid,” writing both traditional and self-published books. Other genres are trickier, however. Memoirs are notoriously hard to sell, either to publishing companies or self-published to readers, unless you’re already famous. Niche topics, like regional history, might have too small an audience for big publishers to profit, making self-publishing the only way to share the information. On the other hand, children’s books tend to struggle with self-publishing. Many self-published books are e-books only, and fewer children have e-readers. Most children’s books are also bought by adults, like parents or grandparents, who are looking for physical gifts and are worried about screen time.

"================ <TEXT PASSAGE> ======= Your two main options are traditional publishing with a publishing company, or self-publishing through a platform like IngramSpark, Amazon Kindle Direct, or Indie Author Project / Biblioboard. Many authors have strong opinions about which publishing path is best. Traditional publishing offers support from a full team of experts, including editors, designers, and salespeople, often leading to higher sales and a more polished product. However, traditional publishing is notoriously slow and has historically excluded writers from marginalized groups. Self-publishing offers a quicker way to share your book with readers, as well as freedom from industry pressure to write something “sellable.” However, self-published books can suffer from the lack of professional editing and design, and self-published authors take on the hard work of sales, marketing, and distribution. There’s no one right answer. It depends on your personal goals for writing and publication. Below are three questions to help you decide whether traditional publishing or self-publishing is right for you. You want to spend it writing, of course! However, writing is only one part of an author’s career. Authors also spend time revising, marketing their books, and, if you’re pursuing traditional publishing, finding an agent. Most major publishers do not accept submissions directly from writers. Instead, writers find agents who sell their work to publishers in return for around 15% of profits. Having an agent signals to publishers that your book is good enough for at least one person to stake their career on it. And having an agent means you can focus on writing your next book instead of researching every editor at every imprint of every publishing house, and then becoming an expert in negotiating your own publishing contract. However, you will have to put that research and negotiation power toward querying agents. During the querying process, writers email a brief pitch of their work to agents who may be interested. Querying is often considered one of the most difficult parts of traditional publishing, as writers may receive hundreds of rejections over multiple books. Rejection isn’t always bad, though. It can be an invitation to revise and improve your work. Writing is hard, and no one gets it right on the first try. Early drafts of a book get the idea out of your brain and into words. Later drafts make the story reach its full potential. Traditional publishing has multiple rounds of agent and editor revisions baked into the process. Self-publishing does not. Self-published writers decide for themselves how much to revise their work before sharing it. Some self-published authors hire freelance editors. Some trust friends and family for feedback. Others skip revisions, share the work as-is, and move on to their next project. Skipping revisions can have negative impacts on book quality, but ultimately, it’s a question of whether you’d prefer to spend your time telling new stories or polishing old ones. Before publication, it may seem like traditional publishing takes a lot more work than self-publishing. However, once a book is published, the tables turn. Traditional publishing includes whole teams of people working behind the scenes to determine how much books should cost, negotiate deals with booksellers, review books so teachers and librarians know which ones to buy, and more. If you’re self-publishing, you are those teams of people. You do all the work of pricing, formatting, selling, marketing, distributing, and more. Even if you only want to e-publish, you still have to format your own manuscript, or hire a professional to do it for you, and submit to the online platform(s) of your choice. You have to figure out a marketing strategy that will make you stand out, not only among self-published or indie authors, but also against professional marketing teams from billion-dollar publishing companies. It’s hard work! And it takes time away from writing. Whether you choose traditional or self-publishing, writing is only one aspect of your career. It’s worth asking whether you’d prefer to spend time querying agents or becoming an expert in everything from typesetting to book distribution. It’s also worth considering why you want a writing career in the first place. Every writer has their own reasons for writing. We love it. We don’t know how to live without it. We want to tell our story or make the world a better place. Usually, the answer is not money. And that’s okay! Creative expression can be fun and freeing and deeply meaningful, even if you never monetize it. If you know up front—before sending 100 query letters or spending hours and hours typesetting your manuscript—that writing is not a financial or career goal, you can save yourself a lot of stress and rejection. However, if you do want to make writing a financially viable career, it’s important to know how and when you get paid through traditional or self-publishing. In traditional publishing, when your agent sells your book to a publisher, you are paid an advance. An advance is a lump sum that the company expects to earn back later through your book sales. Advances vary wildly in amount. Small, indie publishers might pay as low as $1,000-$2,000. Large publishers might offer up to six figures or more. The amount depends on factors like genre, target age group, and whether it’s your first book or you’re more advanced in your career. After your book earns out its advance—meaning the publisher made back the money they paid you—then you earn royalties on every additional copy sold. In traditional publishing, writers do not pay anything up front. If your agent or editor charges “reading fees,” or if you are asked to pay for any part of book design or production, you are being scammed. This is an important distinction because self-publishing works differently. In self-publishing, your income depends entirely on how many books you sell. There are no advances. You may also have to pay up-front, depending on which parts of book production you want to tackle yourself and which parts (if any) you’d like to hire experts to manage for you. Up-front self-publishing costs could include hiring a freelance editor or book designer, or paying to print your book if you plan to sell hard copies. There are free e-publishing options, such as Kindle Direct or Indie Author Project / Biblioboard. For hard copies, a print-on-demand model like IngramSpark can save you from paying to print and warehouse extra books that you’re unable to sell. It can be difficult to know whether it’s financially better to shop around your manuscript a little longer, waiting for that big advance, or whether you should go ahead and self-publish to start selling copies now. The answer can depend on what genre you’re writing in and what age group you’re writing for. Your book’s length and genre, as well as the age of your readers, can have a huge impact on whether you’re able to make money in traditional or self-publishing. Sometimes, both can be profitable. Romance is a rare genre that both tops traditional publishing sales and has recently seen significant income growth for self-published authors. In fact, many romance writers are now “hybrid,” writing both traditional and self-published books. Other genres are trickier, however. Memoirs are notoriously hard to sell, either to publishing companies or self-published to readers, unless you’re already famous. Niche topics, like regional history, might have too small an audience for big publishers to profit, making self-publishing the only way to share the information. On the other hand, children’s books tend to struggle with self-publishing. Many self-published books are e-books only, and fewer children have e-readers. Most children’s books are also bought by adults, like parents or grandparents, who are looking for physical gifts and are worried about screen time. https://nolalibrary.org/2023/06/27/traditional-publishing-vs-self-publishing/ ================ <QUESTION> ======= I would like to understand the differences between traditional and self-publishing. How do I know which route to go? Which route has the potential for a greater profit? ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

I recently acquired a collection of about 50 glass plate photographs, and I want to digitize them. Please list and give detailed descriptions of the steps needed to do this. Also include a list of equipment I'll need.

Digitizing Glass Plate Photography Digitization refers to the process of creating digital images of physical items, yet this process requires many steps. And while the equipment needed for digitizing glass photographs exists in a variety of price points, the basic tenets remain the same: imaging, editing, describing (with metadata), archiving, and sharing. Imaging To image glass photographs, it is necessary to have a camera and a light source, as glass photographs must be backlit to render the images visible. Best practices recommend a flat lightboard for consistent illumination, a camera copy stand, and a camera with focus peaking and aperture priority to achieve the highest quality images. For the lightboard, also known as a light table, it is recommended to use one with a coloring rendering index of 90+ and 5000-5500k light temperature. Cameras should be mounted to the copy stand with overhead mounts to ensure consistent imaging; best practice is to use a level to ensure the camera and light table are parallel to each other. Editing While editing images for commercial or marketing practices is acceptable, editing photographs of physical items for archival purposes is typically not recommended. To edit the images for archival purposes, it is best practice to make only minimal adjustments, such as converting negatives to positives. For copies of the digitized images to be used for marketing purposes, etc., it is acceptable to edit the contrast, exposure, brightness, etc. or to touchup breaks in the glass or emulsion. It is also acceptable at this phase to add watermarks or logos to copies of the digitized images, however this should again only be done with non-archival copies of the images. Description—Metadata The metadata for glass photographs may come in the form of supplemental materials; institutional, personal, or expert knowledge; or may even be on the plates themselves, written onto the paper edgings or directly on the glass. Metadata from this information can be created for the entire collection, specific boxes or containers, individual images, or a combination thereof. This information not only helps users in the search and discovery phases of seeking digitized images, but it also helps organize and adds context and provenance to digital images. Workflows for adding metadata vary. Some prefer to work with the metadata after the glass photographs are imaged, while others prefer to have the metadata completely organized before imaging. The timing of metadata inclusion must be made by considering the conditions of the glass photographs and their storage facilities, the level of metadata available, and the availability of staff dedicated to the process. The best way to add metadata to digitized images is to use a program that embeds metadata within the image. This guarantees that the metadata is always connected to the image and can be extracted from the EXIF data. Adobe Lightroom and similar programs can perform this function. In addition, it is also helpful to keep local files, software, or databases that detail the metadata associated with the images in the glass photographs. Storage—Digital Archives To archive the digitized images, it is important to follow the 3-2-1 digital preservation standard by saving three copies of every digital image, in two different file formats, with one copy saved in a different location. RAW or TIFF file types are best for long-term storage because they are less prone to bit-rot and therefore less likely to degrade over time. Uncompressed TIFF files are typically quite large, which allows for printing at considerable scale without pixelating, however they also take up much more storage space. These file formats are typically best saved in rarely used storage locations, as their size slows down most computing processes, and the full-size uncompressed images are not frequently needed for everyday use. In practice, the authors have found it best to take the initial images of the glass plates in RAW format, and then save additional copies in compressed file formats. Commonly used compressed file formats include JPEG and PNG. These files are smaller and load faster on websites and computers, which allows for easier shared use. Sharing Finally, it is important to share digitized images of glass photographs, both to educate others on the unique existence of these items while also limiting contact and handling. For the authors, sharing digitized images and the standards for doing so are the key additions to the updated literature on best practices for glass photographs. Much of the previous literature was written at least a decade ago, and much has changed in the information and communication technology landscape in that time. For glass photograph imaging projects, it is necessary to create multiple points of access to the visual and historical information obtained from these glass plates. Publishing collection information in multimedia form creates a rich resource for researchers and specialists. Images accompanying textual records enhance the collections for audiences of different ages and interests across the world and create a basic resource for interpretative applications to be built on. Work in digital humanities, digital archives, and museum informatics can attest to the audience for and varied applications of these materials. Through the digitization of cultural collections, these resources can be used for multiple purposes, including educational and interpretive research. Digitized collections allow viewers to zoom in and examine details of glass photographs which would not otherwise be seen in a display case or by the naked eye. For cultural institutions, digitization offers the ability to display an entire collection, as large parts of it would not typically be on public display, and to reach those who cannot visit in person. Other benefits include the ability to adjust interpretative applications for users with disabilities or special needs. While social media sites are a natural place to promote such images, they should be used as a secondary location. Best practices recommend a primary location for all images to be shared with the public, such as a website, digital asset management system (DAMS), database with a strong graphical user interface (GUI), or dedicated photo storage site such as Flickr. With new technologies and protocols for database searching, the importance of cultural institutions offering digital access to their collections allows for the possibility of cross-collection and cross-institutional searching.

[question] I recently acquired a collection of about 50 glass plate photographs, and I want to digitize them. Please list and give detailed descriptions of the steps needed to do this. Also include a list of equipment I'll need. ===================== [text] Digitizing Glass Plate Photography Digitization refers to the process of creating digital images of physical items, yet this process requires many steps. And while the equipment needed for digitizing glass photographs exists in a variety of price points, the basic tenets remain the same: imaging, editing, describing (with metadata), archiving, and sharing. Imaging To image glass photographs, it is necessary to have a camera and a light source, as glass photographs must be backlit to render the images visible. Best practices recommend a flat lightboard for consistent illumination, a camera copy stand, and a camera with focus peaking and aperture priority to achieve the highest quality images. For the lightboard, also known as a light table, it is recommended to use one with a coloring rendering index of 90+ and 5000-5500k light temperature. Cameras should be mounted to the copy stand with overhead mounts to ensure consistent imaging; best practice is to use a level to ensure the camera and light table are parallel to each other. Editing While editing images for commercial or marketing practices is acceptable, editing photographs of physical items for archival purposes is typically not recommended. To edit the images for archival purposes, it is best practice to make only minimal adjustments, such as converting negatives to positives. For copies of the digitized images to be used for marketing purposes, etc., it is acceptable to edit the contrast, exposure, brightness, etc. or to touchup breaks in the glass or emulsion. It is also acceptable at this phase to add watermarks or logos to copies of the digitized images, however this should again only be done with non-archival copies of the images. Description—Metadata The metadata for glass photographs may come in the form of supplemental materials; institutional, personal, or expert knowledge; or may even be on the plates themselves, written onto the paper edgings or directly on the glass. Metadata from this information can be created for the entire collection, specific boxes or containers, individual images, or a combination thereof. This information not only helps users in the search and discovery phases of seeking digitized images, but it also helps organize and adds context and provenance to digital images. Workflows for adding metadata vary. Some prefer to work with the metadata after the glass photographs are imaged, while others prefer to have the metadata completely organized before imaging. The timing of metadata inclusion must be made by considering the conditions of the glass photographs and their storage facilities, the level of metadata available, and the availability of staff dedicated to the process. The best way to add metadata to digitized images is to use a program that embeds metadata within the image. This guarantees that the metadata is always connected to the image and can be extracted from the EXIF data. Adobe Lightroom and similar programs can perform this function. In addition, it is also helpful to keep local files, software, or databases that detail the metadata associated with the images in the glass photographs. Storage—Digital Archives To archive the digitized images, it is important to follow the 3-2-1 digital preservation standard by saving three copies of every digital image, in two different file formats, with one copy saved in a different location. RAW or TIFF file types are best for long-term storage because they are less prone to bit-rot and therefore less likely to degrade over time. Uncompressed TIFF files are typically quite large, which allows for printing at considerable scale without pixelating, however they also take up much more storage space. These file formats are typically best saved in rarely used storage locations, as their size slows down most computing processes, and the full-size uncompressed images are not frequently needed for everyday use. In practice, the authors have found it best to take the initial images of the glass plates in RAW format, and then save additional copies in compressed file formats. Commonly used compressed file formats include JPEG and PNG. These files are smaller and load faster on websites and computers, which allows for easier shared use. Sharing Finally, it is important to share digitized images of glass photographs, both to educate others on the unique existence of these items while also limiting contact and handling. For the authors, sharing digitized images and the standards for doing so are the key additions to the updated literature on best practices for glass photographs. Much of the previous literature was written at least a decade ago, and much has changed in the information and communication technology landscape in that time. For glass photograph imaging projects, it is necessary to create multiple points of access to the visual and historical information obtained from these glass plates. Publishing collection information in multimedia form creates a rich resource for researchers and specialists. Images accompanying textual records enhance the collections for audiences of different ages and interests across the world and create a basic resource for interpretative applications to be built on. Work in digital humanities, digital archives, and museum informatics can attest to the audience for and varied applications of these materials. Through the digitization of cultural collections, these resources can be used for multiple purposes, including educational and interpretive research. Digitized collections allow viewers to zoom in and examine details of glass photographs which would not otherwise be seen in a display case or by the naked eye. For cultural institutions, digitization offers the ability to display an entire collection, as large parts of it would not typically be on public display, and to reach those who cannot visit in person. Other benefits include the ability to adjust interpretative applications for users with disabilities or special needs. While social media sites are a natural place to promote such images, they should be used as a secondary location. Best practices recommend a primary location for all images to be shared with the public, such as a website, digital asset management system (DAMS), database with a strong graphical user interface (GUI), or dedicated photo storage site such as Flickr. With new technologies and protocols for database searching, the importance of cultural institutions offering digital access to their collections allows for the possibility of cross-collection and cross-institutional searching. https://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=1173&context=westernarchives ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Draw your answer from the passage below only.

Write a short summary about how this acquisition will affect the video game market as a whole.

On January 18, 2022, Microsoft Corp. announced plans to acquire Activision Blizzard Inc., a video game company, for $68.7 billion.1 The Federal Trade Commission (FTC) is reviewing the acquisition,2 as provided under the Hart-Scott-Rodino Act (HSR),3 to determine whether its effect might be “substantially to lessen competition”—a violation of Section 7 of the Clayton Act. 4 Competition authorities in other countries are reviewing Microsoft’s proposed acquisition as well.5 The companies have said they expect to complete the acquisition before June 30, 2023.6 In recent decades, enforcement of antitrust laws has typically focused on how a proposed merger or acquisition might affect consumers, such as by reducing price competition in relevant product markets. Some of the FTC’s actions and statements over the last two years suggest that in its review of Microsoft’s proposed acquisition, the FTC may be considering other factors that are discussed in this report.7 This report discusses Microsoft’s proposed acquisition of Activision Blizzard, including some of the potential effects on existing product markets, labor markets, and on product markets that do not currently exist but may develop in the future. The report also provides some considerations for Congress, discussing some bills that may affect Microsoft’s proposed acquisition or Microsoft’s future behavior if the acquisition is completed. The Video Game Industry The video game industry can be separated into three components: developers or gaming studios that create and design video games; publishers who market and monetize the video games; and distributors who provide the video games to consumers.8 Video games are most commonly played on game consoles, personal computers (PCs), and mobile devices (Figure 1). Although some retailers sell physical copies of video games for consoles and PCs, the majority of video games are sold in digital format;9 games for mobile devices are sold only in digital format. The extent of competition among distributors depends on the format and device used to play the game. The digital format of video games played on a console generally can only be downloaded from a digital store operated by the producer of the console. Games for PCs can be purchased from a selection of digital stores that are operated by various firms,10 including publishers and developers.11 Some of these firms also provide their games as apps on certain mobile devices;12 these are distributed through app stores, such as Google Play and Apple’s App Store. Consoles are typically sold at a loss; the manufacturers then profit from sales of games and subscription services.13 This can incentivize console producers to acquire developers and publishers and offer exclusive content.14 Technological developments have allowed some PCs and other devices, depending on their hardware capabilities, to compete with game consoles.15 For example, early in 2022, Valve Corp. released a handheld PC—Steam Deck—that resembles the Nintendo Switch console but provides features that are typically available on PCs, such as a web browser, and allows users to download third-party software, including other operating systems.16 Some firms have started offering video game subscription services that provide access to multiple games for a monthly fee, meaning users do not need to purchase each individual game.17 Some firms offer cloud gaming, which allows users to play video games using remote servers in data centers, reducing the hardware requirements needed to play the games and expanding the variety of devices that can be used.18 Cloud gaming, however, requires a high-speed internet connection and is not feasible for potential users who do not have access to sufficiently high broadband speeds.19 Subscription services reportedly provide 4% of total revenue in the North American and European video game markets.20 Some firms backed by venture capitalists and large firms that are primarily known for providing other online services have shown interest in entering the video game industry.21 For example, Netflix started offering games on mobile devices on November 2, 2021, and has acquired video game developers.22 These firms may be able to further expand the selection of distributors available for certain devices and potentially increase competition in the industry.23

Write a short summary about how this acquisition will affect the video game market as a whole. Draw your answer from the passage below only. Use 100 words or less. On January 18, 2022, Microsoft Corp. announced plans to acquire Activision Blizzard Inc., a video game company, for $68.7 billion.1 The Federal Trade Commission (FTC) is reviewing the acquisition,2 as provided under the Hart-Scott-Rodino Act (HSR),3 to determine whether its effect might be “substantially to lessen competition”—a violation of Section 7 of the Clayton Act. 4 Competition authorities in other countries are reviewing Microsoft’s proposed acquisition as well.5 The companies have said they expect to complete the acquisition before June 30, 2023.6 In recent decades, enforcement of antitrust laws has typically focused on how a proposed merger or acquisition might affect consumers, such as by reducing price competition in relevant product markets. Some of the FTC’s actions and statements over the last two years suggest that in its review of Microsoft’s proposed acquisition, the FTC may be considering other factors that are discussed in this report.7 This report discusses Microsoft’s proposed acquisition of Activision Blizzard, including some of the potential effects on existing product markets, labor markets, and on product markets that do not currently exist but may develop in the future. The report also provides some considerations for Congress, discussing some bills that may affect Microsoft’s proposed acquisition or Microsoft’s future behavior if the acquisition is completed. The Video Game Industry The video game industry can be separated into three components: developers or gaming studios that create and design video games; publishers who market and monetize the video games; and distributors who provide the video games to consumers.8 Video games are most commonly played on game consoles, personal computers (PCs), and mobile devices (Figure 1). Although some retailers sell physical copies of video games for consoles and PCs, the majority of video games are sold in digital format;9 games for mobile devices are sold only in digital format. The extent of competition among distributors depends on the format and device used to play the game. The digital format of video games played on a console generally can only be downloaded from a digital store operated by the producer of the console. Games for PCs can be purchased from a selection of digital stores that are operated by various firms,10 including publishers and developers.11 Some of these firms also provide their games as apps on certain mobile devices;12 these are distributed through app stores, such as Google Play and Apple’s App Store. Consoles are typically sold at a loss; the manufacturers then profit from sales of games and subscription services.13 This can incentivize console producers to acquire developers and publishers and offer exclusive content.14 Technological developments have allowed some PCs and other devices, depending on their hardware capabilities, to compete with game consoles.15 For example, early in 2022, Valve Corp. released a handheld PC—Steam Deck—that resembles the Nintendo Switch console but provides features that are typically available on PCs, such as a web browser, and allows users to download third-party software, including other operating systems.16 Some firms have started offering video game subscription services that provide access to multiple games for a monthly fee, meaning users do not need to purchase each individual game.17 Some firms offer cloud gaming, which allows users to play video games using remote servers in data centers, reducing the hardware requirements needed to play the games and expanding the variety of devices that can be used.18 Cloud gaming, however, requires a high-speed internet connection and is not feasible for potential users who do not have access to sufficiently high broadband speeds.19 Subscription services reportedly provide 4% of total revenue in the North American and European video game markets.20 Some firms backed by venture capitalists and large firms that are primarily known for providing other online services have shown interest in entering the video game industry.21 For example, Netflix started offering games on mobile devices on November 2, 2021, and has acquired video game developers.22 These firms may be able to further expand the selection of distributors available for certain devices and potentially increase competition in the industry.23

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

I recently got a credit card that offers cash back when I shop in certain places but I'm new to the concept. In 200 words or less, what are some great ways that it can be used? Additionally, what other credit card would be great for me when it comes to retail deals through the card?

Take advantage of issuers’ shopping portals Before you shop, whether in-person or online, look for card-linked offers from your credit card issuer. If you have the Chase Freedom Flex or Chase Freedom Unlimited, for example, check the Shop through Chase portal to earn more cash back on all your purchases. Although the stores in the Chase shopping portal vary, they frequently include options like Walmart, Sephora, Best Buy and Macy’s. Other issues have their own portals — with Barclaycard you can shop on RewardsBoost, and with a Capital One card you get access to Capital One Shopping. Some issuers offer additional rewards opportunities as well. American Express, Chase, and Capital One have programs — Amex Offers, Chase Offers and Capital One Offers, respectively — through which you can opt in to earn additional cash back from select retailers. For example, with the Capital One QuicksilverOne Cash Rewards Credit Card, you can earn more cash back with particular retailers. To do so, log in to your Capital One account and navigate to the offers portal. In the portal, click “Get this deal” to be taken to a retailer’s site to shop and earn additional rewards at check out. Generally speaking, these offers are found in your online account, have limited redemption windows and must be accepted individually. Cash back percentages vary from store to store, and there are usually limits that cap how much additional cash back you can earn. Make the most of cash back apps If you want to earn more cash back for online purchases, you often can increase your earnings through the use of cash back apps. Cash back apps and sites like Dosh, Ibotta and Rakuten (formerly Ebates) give you a percentage of your spending back on qualifying purchases — on top of the cash back you’re earning on your credit card. For example, Rakuten lets you earn additional cash back when you click through the website before you shop with stores like Kohl’s, Macy’s, Nordstrom, Old Navy and Priceline.com. Use your cash back wisely While maximizing cash back earned on spending always makes sense, that’s only part of the equation. You also need to redeem your cash back in ways that make sense for your goals, whether you want to reduce the amount you owe on your credit card bill, you want to splurge for a fun purchase or you hope to utilize rewards to improve your finances in some way. Consider the following tips to get the most out of your cash back rewards each year: Redeem your cash back as statement credits One of the easiest ways to redeem cash back is for statement credits to your account. This redemption effectively lowers the amount you owe on your credit card bill, thus helping you save money over time. If you sign up for the Wells Fargo Active Cash® Card to earn 2% cash back on all purchases and redeem your rewards for cash back, for example, you would ultimately save 2% on everything you buy with your card. Just remember that rewards only get you “ahead” if you pay your credit card bill in full each month and avoid interest. If you’re paying 20% in credit card interest or more to earn 2% cash back, you’re not doing yourself any favors. Save your cash back for a big purchase You can also save up your rewards for a purchase you want to make down the line, whether it’s a splurge purchase you don’t want to cover in cash or you need to buy something for your everyday life. In either case, most cash back credit cards let you grow your rewards balance over time until you’re ready to use it. Keep in mind: Using rewards for merchandise won't always get you the best value, and that you'll want to be strategic if you go this route. As an example, cash back credit cards from Chase offer 1 cent per point for statement credit redemptions but only 0.8 cents per point for purchases through Amazon.com or PayPal. If you wanted to use rewards for an Amazon or PayPal purchase, it would make more sense to pay for the purchase with your card outright then redeem rewards for statement credits after the fact. Use your cash back to pay down debt You can also use rewards to pay off some types of debt, either directly depending on the card you have or indirectly by redeeming for cash back. In terms of options that let you redeem rewards for debt payments, some Wells Fargo credit cards (including the Wells Fargo Active Cash® Card) let you redeem cash back toward a Wells Fargo mortgage in addition to options like gift cards and statement credits. Many cash back credit cards also let you redeem rewards for a check in the mail, which you could deposit into a bank account and use for debt payments.

[question] I recently got a credit card that offers cash back when I shop in certain places but I'm new to the concept. In 200 words or less, what are some great ways that it can be used? Additionally, what other credit card would be great for me when it comes to retail deals through the card? ===================== [text] Take advantage of issuers’ shopping portals Before you shop, whether in-person or online, look for card-linked offers from your credit card issuer. If you have the Chase Freedom Flex or Chase Freedom Unlimited, for example, check the Shop through Chase portal to earn more cash back on all your purchases. Although the stores in the Chase shopping portal vary, they frequently include options like Walmart, Sephora, Best Buy and Macy’s. Other issues have their own portals — with Barclaycard you can shop on RewardsBoost, and with a Capital One card you get access to Capital One Shopping. Some issuers offer additional rewards opportunities as well. American Express, Chase, and Capital One have programs — Amex Offers, Chase Offers and Capital One Offers, respectively — through which you can opt in to earn additional cash back from select retailers. For example, with the Capital One QuicksilverOne Cash Rewards Credit Card, you can earn more cash back with particular retailers. To do so, log in to your Capital One account and navigate to the offers portal. In the portal, click “Get this deal” to be taken to a retailer’s site to shop and earn additional rewards at check out. Generally speaking, these offers are found in your online account, have limited redemption windows and must be accepted individually. Cash back percentages vary from store to store, and there are usually limits that cap how much additional cash back you can earn. Make the most of cash back apps If you want to earn more cash back for online purchases, you often can increase your earnings through the use of cash back apps. Cash back apps and sites like Dosh, Ibotta and Rakuten (formerly Ebates) give you a percentage of your spending back on qualifying purchases — on top of the cash back you’re earning on your credit card. For example, Rakuten lets you earn additional cash back when you click through the website before you shop with stores like Kohl’s, Macy’s, Nordstrom, Old Navy and Priceline.com. Use your cash back wisely While maximizing cash back earned on spending always makes sense, that’s only part of the equation. You also need to redeem your cash back in ways that make sense for your goals, whether you want to reduce the amount you owe on your credit card bill, you want to splurge for a fun purchase or you hope to utilize rewards to improve your finances in some way. Consider the following tips to get the most out of your cash back rewards each year: Redeem your cash back as statement credits One of the easiest ways to redeem cash back is for statement credits to your account. This redemption effectively lowers the amount you owe on your credit card bill, thus helping you save money over time. If you sign up for the Wells Fargo Active Cash® Card to earn 2% cash back on all purchases and redeem your rewards for cash back, for example, you would ultimately save 2% on everything you buy with your card. Just remember that rewards only get you “ahead” if you pay your credit card bill in full each month and avoid interest. If you’re paying 20% in credit card interest or more to earn 2% cash back, you’re not doing yourself any favors. Save your cash back for a big purchase You can also save up your rewards for a purchase you want to make down the line, whether it’s a splurge purchase you don’t want to cover in cash or you need to buy something for your everyday life. In either case, most cash back credit cards let you grow your rewards balance over time until you’re ready to use it. Keep in mind: Using rewards for merchandise won't always get you the best value, and that you'll want to be strategic if you go this route. As an example, cash back credit cards from Chase offer 1 cent per point for statement credit redemptions but only 0.8 cents per point for purchases through Amazon.com or PayPal. If you wanted to use rewards for an Amazon or PayPal purchase, it would make more sense to pay for the purchase with your card outright then redeem rewards for statement credits after the fact. Use your cash back to pay down debt You can also use rewards to pay off some types of debt, either directly depending on the card you have or indirectly by redeeming for cash back. In terms of options that let you redeem rewards for debt payments, some Wells Fargo credit cards (including the Wells Fargo Active Cash® Card) let you redeem cash back toward a Wells Fargo mortgage in addition to options like gift cards and statement credits. Many cash back credit cards also let you redeem rewards for a check in the mail, which you could deposit into a bank account and use for debt payments. https://www.bankrate.com/credit-cards/cash-back/maximize-cash-back-strategy/ ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

What is the medication Metformin used for and what are some potential side effects involved in its usage? Make your response no less than 150 words.

Why is this medication prescribed? Metformin is used alone or with other medications, including insulin, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body's response to insulin, a natural substance that controls the amount of glucose in the blood. Metformin is not used to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood). Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes. How should this medicine be used? Metformin comes as a tablet, an extended-release (long-acting) tablet, and a solution (liquid) to take by mouth. The solution is usually taken with meals one or two times a day. The regular tablet is usually taken with meals two or three times a day. The extended-release tablet is usually taken once daily with the evening meal. To help you remember to take metformin, take it around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take metformin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Swallow metformin extended-release tablets whole; do not split, chew, or crush them. Your doctor may start you on a low dose of metformin and gradually increase your dose not more often than once every 1–2 weeks. You will need to monitor your blood sugar carefully so your doctor will be able to tell how well metformin is working. Metformin controls diabetes but does not cure it. Continue to take metformin even if you feel well. Do not stop taking metformin without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient. Other uses for this medicine This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Before taking metformin, tell your doctor and pharmacist if you are allergic to metformin, any of the ingredients of metformin liquid or tablets, or any other medications. Ask your pharmacist or check the manufacturer's patient information for a list of the ingredients. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had low levels of vitamin B12 in your body or any other medical conditions, especially those mentioned in the IMPORTANT WARNING section. tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking metformin, call your doctor. tell your doctor if you eat less or exercise more than usual. This can affect your blood sugar. Your doctor will give you instructions if this happens. What special dietary instructions should I follow? Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. It is important to eat a healthful diet. What should I do if I forget a dose? Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. What side effects can this medication cause? This medication may cause changes in your blood sugar. You should know the symptoms of low and high blood sugar and what to do if you have these symptoms. Metformin may cause side effects. Tell your doctor if any of these symptoms are severe, do not go away, go away and come back, or do not begin for some time after you begin taking metformin: diarrhea nausea stomach discomfort gas indigestion constipation lack of energy or weakness change in sense of taste headache Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency treatment: chest pain Metformin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication. If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

"================ <TEXT PASSAGE> ======= Why is this medication prescribed? Metformin is used alone or with other medications, including insulin, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body's response to insulin, a natural substance that controls the amount of glucose in the blood. Metformin is not used to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood). Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes. How should this medicine be used? Metformin comes as a tablet, an extended-release (long-acting) tablet, and a solution (liquid) to take by mouth. The solution is usually taken with meals one or two times a day. The regular tablet is usually taken with meals two or three times a day. The extended-release tablet is usually taken once daily with the evening meal. To help you remember to take metformin, take it around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take metformin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Swallow metformin extended-release tablets whole; do not split, chew, or crush them. Your doctor may start you on a low dose of metformin and gradually increase your dose not more often than once every 1–2 weeks. You will need to monitor your blood sugar carefully so your doctor will be able to tell how well metformin is working. Metformin controls diabetes but does not cure it. Continue to take metformin even if you feel well. Do not stop taking metformin without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient. Other uses for this medicine This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Before taking metformin, tell your doctor and pharmacist if you are allergic to metformin, any of the ingredients of metformin liquid or tablets, or any other medications. Ask your pharmacist or check the manufacturer's patient information for a list of the ingredients. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had low levels of vitamin B12 in your body or any other medical conditions, especially those mentioned in the IMPORTANT WARNING section. tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking metformin, call your doctor. tell your doctor if you eat less or exercise more than usual. This can affect your blood sugar. Your doctor will give you instructions if this happens. What special dietary instructions should I follow? Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. It is important to eat a healthful diet. What should I do if I forget a dose? Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. What side effects can this medication cause? This medication may cause changes in your blood sugar. You should know the symptoms of low and high blood sugar and what to do if you have these symptoms. Metformin may cause side effects. Tell your doctor if any of these symptoms are severe, do not go away, go away and come back, or do not begin for some time after you begin taking metformin: diarrhea nausea stomach discomfort gas indigestion constipation lack of energy or weakness change in sense of taste headache Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency treatment: chest pain Metformin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication. If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088). https://medlineplus.gov/druginfo/meds/a696005.html ================ <QUESTION> ======= What is the medication Metformin used for and what are some potential side effects involved in its usage? Make your response no less than 150 words. ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Answer the question using only the text provided with no help from external sources or prior knowledge.

What are the challenges associated with mobile AI?

With dedicated on-device AI chipsets, mobile devices will have better knowledge of the user's needs, being able to deliver personalized services that will make smartphones more intelligent. Beyond speed and efficiency, on-device AI offers greater security by providing real-time malware detection, recognizing if the device is being misused by identifying user behavior, and spam detection over emails and other apps. Among the applications and features that will benefit first from on-device AI are:  Virtual digital assistants. By being less dependent on cloud AI and connectivity, virtual assistants can become the main method for users to interact with the devices.  Augmented reality. Augmented reality will also see similar benefits, as it requires computation to take place in the cloud.  Cameras. Having an on-device processor that constantly analyzes what the camera "sees" as users take photos or adjust the brightness, ISO sensitivity, color temperature, and exposure duration every time they press the shutter button, and accurately selecting the right scene mode automatically, will have an impact on the user experience.  Well-being and healthcare. By delivering faster performance — regardless of the quality of the network, while providing optimal protection of user data — many apps will be able to send notifications to the user (and his or her doctor) in response to real-time analysis of patient data and data collected from wearable devices. This will predict health events, enabling users to seek medical advice and for doctors to assist patients when a medical condition or threat is detected by an AI algorithm. Bringing Intelligent Mobile Devices Into Our Lives AI will disrupt the way users interact with smartphones in the future, making it work for us. Going to the cinema, for example, will be a completely different experience from the one we have today: 1. Someone with an intelligent phone is walking down the street and sees an ad for the latest blockbuster movie. On pointing the phone at the ad, the camera recognizes the movie, suggests how likely they are to enjoy it, how much it matches their preferences, and prompting them to ask if it should buy tickets. 2. The phone checks the calendar and suggests when to get the tickets, based on the commitments and appointments for the week, as well as the best theater based on the predicted location for the day. The phone then sends a message to the person who usually goes along, suggesting the movie and asking if they want to come. 3. The phone buys the tickets and stores them in its digital wallet. 4. On the day, the phone confirms availability and suggests having dinner before the movie, at a nearby restaurant bookmarked on the maps app, reminding the user about the type of food served. After confirmation by the user, the phone makes reservations on their behalf. 5. Based on the traffic, the phone sends a reminder when it is time to leave and, if late, it sends an email to the restaurant with an estimated time of arrival. It automatically provides directions to the restaurant from the car park. 6. At the theater the phone automatically displays the ticket on the home screen for faster scan. One single action triggered from the camera will create a chain of actions that will help people manage their lives. AI will make technology work for everyone, rather than people having to adapt to the technology's limitations. Smartphones will learn who the users are, what they do and what they want to do, and deliver a new user experience, one that is not yet available, effortlessly. AI will enable phones to become intelligent and truly personal digital assistants, and it is on-device AI that will be the engine to make this happen. Benefits of Mobile AI The opportunities for always-on devices that do most of their intelligent computing on the device are enormous. Running AI on the device rather than in the cloud offers different benefits too:  No latency. In many cases, running AI entirely in the cloud will have an impact for applications that need to work in real time and are latency-sensitive, such as missioncritical applications and driverless cars. Such applications need to rely on instantaneous responses and cannot afford the roundtrip time or operate when there is variable network coverage.  Increased security and privacy. AI algorithms look for patterns in the data at an unprecedented scale. The data collected by the phone will require a roundtrip to the cloud if no AI capability is available on the device. Being able to perform AI algorithms on the device will provide better security due to the low volumes of data exchanged over the network. But it will also provide better privacy, as the AI algorithms will not have to process and store the information in the cloud. The cloud is used only to train the algorithms. This is paramount in today's environment with new European legislation (GDPR) that aims to provide a set of standardized data protection laws across member countries, but also to reinforce the data protection rights of individuals.  On-device learning. Although most of the training will happen in the cloud, and the smartphone has inference capabilities, it still needs to learn the user's behavior so it can deliver automated, personalized experiences. On-device learning enables training capabilities on the mobile device, so the data does not need to travel to the cloud or be stored outside the device. This process can be triggered while the device is idle, which allows power saving and ensures no interruptions of other features.  Efficiency. Running AI on the device reduces network traffic, as less data is transferred via the network to the cloud, and improves performance as apps that need to run in real time can achieve lower latency levels on the device.  Power saving. Power consumption will be reduced, as the device does not need to constantly upload and download AI-related data to be able to process AI algorithms. This will have a positive effect on battery life and, by extending it, will improve user experience. Challenges of Delivering Mobile AI Bringing machine learning and deep learning algorithms to the edge is essential to lower their data computation requirements, while enabling mobile devices with chipsets that can process some of those algorithms on the device. AI workloads are very compute-intensive. Optimizing AI algorithms for use on mobile is a huge challenge, as is the impact on battery life of the intensive computational AI algorithms on a real-time and always-on environment. Another important challenge with on-device AI is the need to train the algorithms. This requires vast amounts of data. The quality and quantity of data is key to successful machine learning. Depending on the complexity of the model and the amount of data, training can take place in the device or in the cloud. Large models tend to require a lot of processing, which is only available in cloud platforms. Some of the predictions needed from AI algorithms require data that is already available on the user's device and no other sources are needed to be trained. However, to train and run large, complicated neural-network models on mobile devices with less capabilities than large servers is a challenge. A fundamental challenge of offering on-device AI is related to the nature of the smartphone. Designing a chipset that delivers the performance required by highly demanding AI algorithms with the restrictions of smartphones in terms of size, power supply, power consumption, and heat management is a major challenge. "Mobile SoCs have to deliver the best possible performance, while ensuring the highest possible density of core functions with optimal use of energy. The [Huawei] Kirin 970's development team introduced a new, innovative HiAI mobile computing architecture with a dedicated NPU," said Victor Dragnea from Huawei. Developing an AI Ecosystem AI platforms provide developer toolkits to build applications using AI algorithms. They combine a variety of algorithms with data that can be used directly by developers, without having to build them from scratch. Some of the functionality includes image recognition, natural language processing, voice recognition, predictive analytics, and other machine learning and deep learning capabilities. An important part of bringing AI to smartphones is the creation of an AI ecosystem. This is vital to expand the capabilities of the dedicated AI chipsets from a few features on the phone to third-party apps. By providing SDKs and APIs, phone makers will enable developers and partners to find new uses for AI computing capabilities. Huawei is positioning the Kirin 970 as an "open platform for mobile AI." The company emphasizes that the chipset will work with any AI framework, such as Caffe2 and TensorFlow, in order for any app to access the capabilities of the NPU and AI features.

System Instruction: Answer the question using only the text provided with no help from external sources or prior knowledge. User question: What are the challenges associated with mobile AI? Context block: With dedicated on-device AI chipsets, mobile devices will have better knowledge of the user's needs, being able to deliver personalized services that will make smartphones more intelligent. Beyond speed and efficiency, on-device AI offers greater security by providing real-time malware detection, recognizing if the device is being misused by identifying user behavior, and spam detection over emails and other apps. Among the applications and features that will benefit first from on-device AI are:  Virtual digital assistants. By being less dependent on cloud AI and connectivity, virtual assistants can become the main method for users to interact with the devices.  Augmented reality. Augmented reality will also see similar benefits, as it requires computation to take place in the cloud.  Cameras. Having an on-device processor that constantly analyzes what the camera "sees" as users take photos or adjust the brightness, ISO sensitivity, color temperature, and exposure duration every time they press the shutter button, and accurately selecting the right scene mode automatically, will have an impact on the user experience.  Well-being and healthcare. By delivering faster performance — regardless of the quality of the network, while providing optimal protection of user data — many apps will be able to send notifications to the user (and his or her doctor) in response to real-time analysis of patient data and data collected from wearable devices. This will predict health events, enabling users to seek medical advice and for doctors to assist patients when a medical condition or threat is detected by an AI algorithm. Bringing Intelligent Mobile Devices Into Our Lives AI will disrupt the way users interact with smartphones in the future, making it work for us. Going to the cinema, for example, will be a completely different experience from the one we have today: 1. Someone with an intelligent phone is walking down the street and sees an ad for the latest blockbuster movie. On pointing the phone at the ad, the camera recognizes the movie, suggests how likely they are to enjoy it, how much it matches their preferences, and prompting them to ask if it should buy tickets. 2. The phone checks the calendar and suggests when to get the tickets, based on the commitments and appointments for the week, as well as the best theater based on the predicted location for the day. The phone then sends a message to the person who usually goes along, suggesting the movie and asking if they want to come. 3. The phone buys the tickets and stores them in its digital wallet. 4. On the day, the phone confirms availability and suggests having dinner before the movie, at a nearby restaurant bookmarked on the maps app, reminding the user about the type of food served. After confirmation by the user, the phone makes reservations on their behalf. 5. Based on the traffic, the phone sends a reminder when it is time to leave and, if late, it sends an email to the restaurant with an estimated time of arrival. It automatically provides directions to the restaurant from the car park. 6. At the theater the phone automatically displays the ticket on the home screen for faster scan. One single action triggered from the camera will create a chain of actions that will help people manage their lives. AI will make technology work for everyone, rather than people having to adapt to the technology's limitations. Smartphones will learn who the users are, what they do and what they want to do, and deliver a new user experience, one that is not yet available, effortlessly. AI will enable phones to become intelligent and truly personal digital assistants, and it is on-device AI that will be the engine to make this happen. Benefits of Mobile AI The opportunities for always-on devices that do most of their intelligent computing on the device are enormous. Running AI on the device rather than in the cloud offers different benefits too:  No latency. In many cases, running AI entirely in the cloud will have an impact for applications that need to work in real time and are latency-sensitive, such as missioncritical applications and driverless cars. Such applications need to rely on instantaneous responses and cannot afford the roundtrip time or operate when there is variable network coverage.  Increased security and privacy. AI algorithms look for patterns in the data at an unprecedented scale. The data collected by the phone will require a roundtrip to the cloud if no AI capability is available on the device. Being able to perform AI algorithms on the device will provide better security due to the low volumes of data exchanged over the network. But it will also provide better privacy, as the AI algorithms will not have to process and store the information in the cloud. The cloud is used only to train the algorithms. This is paramount in today's environment with new European legislation (GDPR) that aims to provide a set of standardized data protection laws across member countries, but also to reinforce the data protection rights of individuals.  On-device learning. Although most of the training will happen in the cloud, and the smartphone has inference capabilities, it still needs to learn the user's behavior so it can deliver automated, personalized experiences. On-device learning enables training capabilities on the mobile device, so the data does not need to travel to the cloud or be stored outside the device. This process can be triggered while the device is idle, which allows power saving and ensures no interruptions of other features.  Efficiency. Running AI on the device reduces network traffic, as less data is transferred via the network to the cloud, and improves performance as apps that need to run in real time can achieve lower latency levels on the device.  Power saving. Power consumption will be reduced, as the device does not need to constantly upload and download AI-related data to be able to process AI algorithms. This will have a positive effect on battery life and, by extending it, will improve user experience. Challenges of Delivering Mobile AI Bringing machine learning and deep learning algorithms to the edge is essential to lower their data computation requirements, while enabling mobile devices with chipsets that can process some of those algorithms on the device. AI workloads are very compute-intensive. Optimizing AI algorithms for use on mobile is a huge challenge, as is the impact on battery life of the intensive computational AI algorithms on a real-time and always-on environment. Another important challenge with on-device AI is the need to train the algorithms. This requires vast amounts of data. The quality and quantity of data is key to successful machine learning. Depending on the complexity of the model and the amount of data, training can take place in the device or in the cloud. Large models tend to require a lot of processing, which is only available in cloud platforms. Some of the predictions needed from AI algorithms require data that is already available on the user's device and no other sources are needed to be trained. However, to train and run large, complicated neural-network models on mobile devices with less capabilities than large servers is a challenge. A fundamental challenge of offering on-device AI is related to the nature of the smartphone. Designing a chipset that delivers the performance required by highly demanding AI algorithms with the restrictions of smartphones in terms of size, power supply, power consumption, and heat management is a major challenge. "Mobile SoCs have to deliver the best possible performance, while ensuring the highest possible density of core functions with optimal use of energy. The [Huawei] Kirin 970's development team introduced a new, innovative HiAI mobile computing architecture with a dedicated NPU," said Victor Dragnea from Huawei. Developing an AI Ecosystem AI platforms provide developer toolkits to build applications using AI algorithms. They combine a variety of algorithms with data that can be used directly by developers, without having to build them from scratch. Some of the functionality includes image recognition, natural language processing, voice recognition, predictive analytics, and other machine learning and deep learning capabilities. An important part of bringing AI to smartphones is the creation of an AI ecosystem. This is vital to expand the capabilities of the dedicated AI chipsets from a few features on the phone to third-party apps. By providing SDKs and APIs, phone makers will enable developers and partners to find new uses for AI computing capabilities. Huawei is positioning the Kirin 970 as an "open platform for mobile AI." The company emphasizes that the chipset will work with any AI framework, such as Caffe2 and TensorFlow, in order for any app to access the capabilities of the NPU and AI features.

You must answer the prompt by only using the information from the provided context.

What types of risk does Northrup Grumman face within the cyber threat landscape?

Item 1C. Cybersecurity We recognize the critical importance of maintaining the safety and security of our systems and data and have a holistic process for overseeing and managing cybersecurity and related risks. This process is supported by both management and our Board of Directors. The Chief Information Office, which maintains our cybersecurity function, is led by our Chief Information Officer (CIO), who reports to our CEO. The Chief Information Security Officer (CISO) reports to the CIO and generally is responsible for management of cybersecurity risk and the protection and defense of our networks and systems. The CISO manages a team of cybersecurity professionals with broad experience and expertise, including in cybersecurity threat assessments and detection, mitigation technologies, cybersecurity training, incident response, cyber forensics, insider threats and regulatory compliance. Our Board of Directors is responsible for overseeing our enterprise risk management activities in general, and each of our Board committees assists the Board in the role of risk oversight. The full Board receives an update on the Company’s risk management process and the risk trends related to cybersecurity at least annually. The Audit and Risk Committee specifically assists the Board in its oversight of risks related to cybersecurity. To help ensure effective oversight, the Audit and Risk Committee receives reports on information security and cybersecurity from the CISO at least four times a year. In addition, the Company’s Enterprise Risk Management Council (ERMC) considers risks relating to cybersecurity, among other significant risks, and applicable mitigation plans to address such risks. The ERMC is comprised of the Executive Leadership Team, as well as the Chief Accounting Officer, Chief Compliance Officer, Corporate Secretary, Chief Sustainability Officer, Treasurer and Vice President, Internal Audit. The CIO and CISO attend each ERMC meeting. The ERMC meets during the year and receives periodic updates on cybersecurity risks from the CIO and CISO. We have an established process and playbook led by our CISO governing our assessment, response and notifications internally and externally upon the occurrence of a cybersecurity incident. Depending on the nature and severity of an incident, this process provides for escalating notification to our CEO and the Board (including our Lead Independent Director and the Audit and Risk Committee chair). NORTHROP GRUMMAN CORPORATION -22- Our approach to cybersecurity risk management includes the following key elements: • Multi-Layered Defense and Continuous Monitoring – We work to protect our computing environments and products from cybersecurity threats through multi-layered defenses and apply lessons learned from our defense and monitoring efforts to help prevent future attacks. We utilize data analytics to detect anomalies and search for cyber threats. Our Cybersecurity Operations Center provides comprehensive cyber threat detection and response capabilities and maintains a 24x7 monitoring system which complements the technology, processes and threat detection techniques we use to monitor, manage and mitigate cybersecurity threats. From time to time, we engage third party consultants or other advisors to assist in assessing, identifying and/or managing cybersecurity threats. We also periodically use our Internal Audit function to conduct additional reviews and assessments. • Insider Threats – We maintain an insider threat program designed to identify, assess, and address potential risks from within our Company. Our program evaluates potential risks consistent with industry practices, customer requirements and applicable law, including privacy and other considerations. • Information Sharing and Collaboration – We work with government, customer, industry and/or supplier partners, such as the National Defense Information Sharing and Analysis Center and other governmentindustry partnerships, to gather and develop best practices and share information to address cyber threats. These relationships enable the rapid sharing of threat and vulnerability mitigation information across the defense industrial base and supply chain. • Third Party Risk Assessments – We conduct information security assessments before sharing or allowing the hosting of sensitive data in computing environments managed by third parties, and our standard terms and conditions contain contractual provisions requiring certain security protections. • Training and Awareness – We provide awareness training to our employees to help identify, avoid and mitigate cybersecurity threats. Our employees with network access participate annually in required training, including spear phishing and other awareness training. We also periodically host tabletop exercises with management and other employees to practice rapid cyber incident response. • Supplier Engagement – We provide training and other resources to our suppliers to support cybersecurity resiliency in our supply chain. We also require our suppliers to comply with our standard information security terms and conditions, in addition to any requirements from our customers, as a condition of doing business with us, and require them to complete information security questionnaires to review and assess any potential cyber-related risks depending on the nature of the services being provided. While we have experienced cybersecurity incidents in the past, to date none have materially affected the Company or our financial position, results of operations and/or cash flows. We continue to invest in the cybersecurity and resiliency of our networks and to enhance our internal controls and processes, which are designed to help protect our systems and infrastructure, and the information they contain. For more information regarding the risks we face from cybersecurity threats, please see “Risk Factors.” FORWARD-LOOKING STATEMENTS AND PROJECTIONS This Annual Report on Form 10-K and the information we are incorporating by reference contain statements that constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “will,” “expect,” “anticipate,” “intend,” “may,” “could,” “should,” “plan,” “project,” “forecast,” “believe,” “estimate,” “guidance,” “outlook,” “trends,” “goals” and similar expressions generally identify these forward-looking statements. Forward-looking statements include, among other things, statements relating to our future financial condition, results of operations and/or cash flows. Forward-looking statements are based upon assumptions, expectations, plans and projections that we believe to be reasonable when made, but which may change over time. These statements are not guarantees of future performance and inherently involve a wide range of risks and uncertainties that are difficult to predict. Specific risks that could cause actual results to differ materially from those expressed or implied in these forward-looking statements include, but are not limited to, those identified under “Risk Factors” and other important factors disclosed in this report and from time to time in our other SEC filings. These risks and uncertainties are amplified by the global macroeconomic, security and political environments, including inflationary pressures, labor and supply chain challenges, which have caused and will continue to cause significant challenges, instability and uncertainty. They include: Industry and Economic Risks • our dependence on the U.S. government for a substantial portion of our business NORTHROP GRUMMAN CORPORATION

You must answer the prompt by only using the information from the provided context. What types of risk does Northrup Grumman face within the cyber threat landscape? Item 1C. Cybersecurity We recognize the critical importance of maintaining the safety and security of our systems and data and have a holistic process for overseeing and managing cybersecurity and related risks. This process is supported by both management and our Board of Directors. The Chief Information Office, which maintains our cybersecurity function, is led by our Chief Information Officer (CIO), who reports to our CEO. The Chief Information Security Officer (CISO) reports to the CIO and generally is responsible for management of cybersecurity risk and the protection and defense of our networks and systems. The CISO manages a team of cybersecurity professionals with broad experience and expertise, including in cybersecurity threat assessments and detection, mitigation technologies, cybersecurity training, incident response, cyber forensics, insider threats and regulatory compliance. Our Board of Directors is responsible for overseeing our enterprise risk management activities in general, and each of our Board committees assists the Board in the role of risk oversight. The full Board receives an update on the Company’s risk management process and the risk trends related to cybersecurity at least annually. The Audit and Risk Committee specifically assists the Board in its oversight of risks related to cybersecurity. To help ensure effective oversight, the Audit and Risk Committee receives reports on information security and cybersecurity from the CISO at least four times a year. In addition, the Company’s Enterprise Risk Management Council (ERMC) considers risks relating to cybersecurity, among other significant risks, and applicable mitigation plans to address such risks. The ERMC is comprised of the Executive Leadership Team, as well as the Chief Accounting Officer, Chief Compliance Officer, Corporate Secretary, Chief Sustainability Officer, Treasurer and Vice President, Internal Audit. The CIO and CISO attend each ERMC meeting. The ERMC meets during the year and receives periodic updates on cybersecurity risks from the CIO and CISO. We have an established process and playbook led by our CISO governing our assessment, response and notifications internally and externally upon the occurrence of a cybersecurity incident. Depending on the nature and severity of an incident, this process provides for escalating notification to our CEO and the Board (including our Lead Independent Director and the Audit and Risk Committee chair). NORTHROP GRUMMAN CORPORATION -22- Our approach to cybersecurity risk management includes the following key elements: • Multi-Layered Defense and Continuous Monitoring – We work to protect our computing environments and products from cybersecurity threats through multi-layered defenses and apply lessons learned from our defense and monitoring efforts to help prevent future attacks. We utilize data analytics to detect anomalies and search for cyber threats. Our Cybersecurity Operations Center provides comprehensive cyber threat detection and response capabilities and maintains a 24x7 monitoring system which complements the technology, processes and threat detection techniques we use to monitor, manage and mitigate cybersecurity threats. From time to time, we engage third party consultants or other advisors to assist in assessing, identifying and/or managing cybersecurity threats. We also periodically use our Internal Audit function to conduct additional reviews and assessments. • Insider Threats – We maintain an insider threat program designed to identify, assess, and address potential risks from within our Company. Our program evaluates potential risks consistent with industry practices, customer requirements and applicable law, including privacy and other considerations. • Information Sharing and Collaboration – We work with government, customer, industry and/or supplier partners, such as the National Defense Information Sharing and Analysis Center and other governmentindustry partnerships, to gather and develop best practices and share information to address cyber threats. These relationships enable the rapid sharing of threat and vulnerability mitigation information across the defense industrial base and supply chain. • Third Party Risk Assessments – We conduct information security assessments before sharing or allowing the hosting of sensitive data in computing environments managed by third parties, and our standard terms and conditions contain contractual provisions requiring certain security protections. • Training and Awareness – We provide awareness training to our employees to help identify, avoid and mitigate cybersecurity threats. Our employees with network access participate annually in required training, including spear phishing and other awareness training. We also periodically host tabletop exercises with management and other employees to practice rapid cyber incident response. • Supplier Engagement – We provide training and other resources to our suppliers to support cybersecurity resiliency in our supply chain. We also require our suppliers to comply with our standard information security terms and conditions, in addition to any requirements from our customers, as a condition of doing business with us, and require them to complete information security questionnaires to review and assess any potential cyber-related risks depending on the nature of the services being provided. While we have experienced cybersecurity incidents in the past, to date none have materially affected the Company or our financial position, results of operations and/or cash flows. We continue to invest in the cybersecurity and resiliency of our networks and to enhance our internal controls and processes, which are designed to help protect our systems and infrastructure, and the information they contain. For more information regarding the risks we face from cybersecurity threats, please see “Risk Factors.” FORWARD-LOOKING STATEMENTS AND PROJECTIONS This Annual Report on Form 10-K and the information we are incorporating by reference contain statements that constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “will,” “expect,” “anticipate,” “intend,” “may,” “could,” “should,” “plan,” “project,” “forecast,” “believe,” “estimate,” “guidance,” “outlook,” “trends,” “goals” and similar expressions generally identify these forward-looking statements. Forward-looking statements include, among other things, statements relating to our future financial condition, results of operations and/or cash flows. Forward-looking statements are based upon assumptions, expectations, plans and projections that we believe to be reasonable when made, but which may change over time. These statements are not guarantees of future performance and inherently involve a wide range of risks and uncertainties that are difficult to predict. Specific risks that could cause actual results to differ materially from those expressed or implied in these forward-looking statements include, but are not limited to, those identified under “Risk Factors” and other important factors disclosed in this report and from time to time in our other SEC filings. These risks and uncertainties are amplified by the global macroeconomic, security and political environments, including inflationary pressures, labor and supply chain challenges, which have caused and will continue to cause significant challenges, instability and uncertainty. They include: Industry and Economic Risks • our dependence on the U.S. government for a substantial portion of our business NORTHROP GRUMMAN CORPORATION

You base your responses on the provided text and do not use any external knowledge. You also do not use any prior knowledge. Your response should be 3-5 bullet points long, with each bullet point no longer than 1 sentence.

What is pixel density?

1. Introduction This step-by-step guide helps you select the best cameras for your operational requirements and surveillance scenarios. Lack of industry standards and the complexity of the matter cause many integrators to lose sight of a key prerequisite in any installation: the operational requirements or the true purpose of the surveillance. In this guide, we present the Pixel Density Model – a method that allows you to relate the operational requirements of your system to modern surveillance video and IP cameras. 2. Moving into IP Selecting the appropriate surveillance camera to fulfill operational requirements has always been a challenge. With the introduction of IP cameras, and especially through the development of megapixel and HDTV cameras, the need has emerged for a new way to determine how to meet operational requirements. In these six steps, we describe a model to relate operational requirements to modern video and IP cameras. When recommending cameras and discussing what is the “best” camera on the market, it is easy to focus on datasheets and technical specifications. This causes many integrators to lose sight of a key prerequisite in any installation, namely the operational requirements or the actual purpose of the surveillance. Previously when surveillance was all analog, selecting a camera to match an operational requirement was mostly about selecting the appropriate lens since there wasn’t a wide variety of resolutions to choose from. Most CCTV systems are designed to monitor human behavior, so the human body was used as a yardstick. In order to differentiate between diverse types of scenarios, various categories were established based on percentage representation of the height of a human body within the field of view. While not a global standard in any way, it became quite common to distinguish between the need for detection, recognition, and identification. As correct as the percentages in Figure 1 might be for a standard analog resolution, they pose a few challenges when moving into the diverse resolutions of IP cameras. To bridge the gap, attempts have been made to translate from TV lines to pixels to produce tables like the one shown in Figure 2, where the way of thinking about analog operational requirements in terms of percentages has been translated for IP. This might be correct, but it is difficult – if not impossible – to work with complexity such as this in a real-life context. Surely there must be a better way 3. Pixel density The growth of IP surveillance forces us to a make paradigm shift in the way we define our operational requirements. Advancements in camera technology have resulted in a multitude of resolutions and formats. Instead of using vertical height and percentage, we should focus on pixel density in the horizontal dimension. The term pixel density in this context refers to the number of pixels representing the object of our operational requirement – commonly a human, or more specifically, a human face. One reason why we have chosen to use the face is its distinct identifying features. Furthermore, the variances in face widths are less than those of body lengths or widths, which results in a smaller margin of error. The average human face is 16 centimeters wide (= 6.3 inches wide). Following suggested operational requirements from SKL, the Swedish National Laboratory of Forensic Science, and supported by our own test results at Axis Communications, we have chosen to use 80 pixels as the requirement for facial identification for challenging conditions . (see Figure 3). To some, this number might sound high, and in fact some vendors or independent sources recommend 40 pixels for a face or 100 pixels per foot for recognition. The argument behind the higher number is that for identification, there are limited other telltale signs. For recognition, previous knowledge adds factors such as how a person moves – a property easy to observe and recognize, but difficult to identify and describe accurately. To ensure sufficient video quality even if the object isn’t facing the camera straight on, or if the lighting is not optimal, the higher number provides an adequate safety margin. 1 Challenging conditions: Situations with very varying or weak lighting. People, objects and vehicles are seen from an angle where details are in shade, or facing away from the camera. It could also occur in situations where people, objects and vehicles are moving at very high speed through an area. More often occurring in outdoor situations without additional lighting, or indoor situations during very dark conditions. 2 See European Standard EN 50132-7:2012 by CENELEC www.cenelec.eu 3 Good conditions: Situations with decent lighting. People, objects and vehicles are moving at reasonable speed, and seen from an angle where sufficient details are visible. More often occurring in indoor situations where lighting is even, or outdoor situations with additional lighting.

1. Introduction This step-by-step guide helps you select the best cameras for your operational requirements and surveillance scenarios. Lack of industry standards and the complexity of the matter cause many integrators to lose sight of a key prerequisite in any installation: the operational requirements or the true purpose of the surveillance. In this guide, we present the Pixel Density Model – a method that allows you to relate the operational requirements of your system to modern surveillance video and IP cameras. 2. Moving into IP Selecting the appropriate surveillance camera to fulfill operational requirements has always been a challenge. With the introduction of IP cameras, and especially through the development of megapixel and HDTV cameras, the need has emerged for a new way to determine how to meet operational requirements. In these six steps, we describe a model to relate operational requirements to modern video and IP cameras. When recommending cameras and discussing what is the “best” camera on the market, it is easy to focus on datasheets and technical specifications. This causes many integrators to lose sight of a key prerequisite in any installation, namely the operational requirements or the actual purpose of the surveillance. Previously when surveillance was all analog, selecting a camera to match an operational requirement was mostly about selecting the appropriate lens since there wasn’t a wide variety of resolutions to choose from. Most CCTV systems are designed to monitor human behavior, so the human body was used as a yardstick. In order to differentiate between diverse types of scenarios, various categories were established based on percentage representation of the height of a human body within the field of view. While not a global standard in any way, it became quite common to distinguish between the need for detection, recognition, and identification. As correct as the percentages in Figure 1 might be for a standard analog resolution, they pose a few challenges when moving into the diverse resolutions of IP cameras. To bridge the gap, attempts have been made to translate from TV lines to pixels to produce tables like the one shown in Figure 2, where the way of thinking about analog operational requirements in terms of percentages has been translated for IP. This might be correct, but it is difficult – if not impossible – to work with complexity such as this in a real-life context. Surely there must be a better way 3. Pixel density The growth of IP surveillance forces us to a make paradigm shift in the way we define our operational requirements. Advancements in camera technology have resulted in a multitude of resolutions and formats. Instead of using vertical height and percentage, we should focus on pixel density in the horizontal dimension. The term pixel density in this context refers to the number of pixels representing the object of our operational requirement – commonly a human, or more specifically, a human face. One reason why we have chosen to use the face is its distinct identifying features. Furthermore, the variances in face widths are less than those of body lengths or widths, which results in a smaller margin of error. The average human face is 16 centimeters wide (= 6.3 inches wide). Following suggested operational requirements from SKL, the Swedish National Laboratory of Forensic Science, and supported by our own test results at Axis Communications, we have chosen to use 80 pixels as the requirement for facial identification for challenging conditions . (see Figure 3). To some, this number might sound high, and in fact some vendors or independent sources recommend 40 pixels for a face or 100 pixels per foot for recognition. The argument behind the higher number is that for identification, there are limited other telltale signs. For recognition, previous knowledge adds factors such as how a person moves – a property easy to observe and recognize, but difficult to identify and describe accurately. To ensure sufficient video quality even if the object isn’t facing the camera straight on, or if the lighting is not optimal, the higher number provides an adequate safety margin. 1 Challenging conditions: Situations with very varying or weak lighting. People, objects and vehicles are seen from an angle where details are in shade, or facing away from the camera. It could also occur in situations where people, objects and vehicles are moving at very high speed through an area. More often occurring in outdoor situations without additional lighting, or indoor situations during very dark conditions. 2 See European Standard EN 50132-7:2012 by CENELEC www.cenelec.eu 3 Good conditions: Situations with decent lighting. People, objects and vehicles are moving at reasonable speed, and seen from an angle where sufficient details are visible. More often occurring in indoor situations where lighting is even, or outdoor situations with additional lighting. What is pixel density? You base your responses on the provided text and do not use any external knowledge. You also do not use any prior knowledge. Your response should be 3-5 bullet points long, with each bullet point no longer than 1 sentence.

Rely only on the context document, with no outside information.

Based on the document, was the user satisfied with the product?

**AirPod Pro (2nd Gen) Customer Review** the sound quality and bass of these earphones are clear and exceptional for listening to both music and podcasts; it's like i'm hearing all of my favorite music again with new ears, including background harmonies and production qualities that i didn't notice before. they are so lightweight and comfortable, and i haven't had any issues with them falling out, which was a concern for me as someone who goes to the gym and wears glasses. they connected to my apple devices quickly and effortlessly, and they're very aesthetically beautiful and stylish in person. the noise cancellation feature is excellent and effectively blocks out background noise, sometimes so much so that i'm unaware of my surroundings, but the level of noise cancellation and volume can be adjusted based on your surroundings. there is also a feature where siri can read your notifications as they come in, which some people may find useful. you can answer, mute, unmute, and end calls by pressing them, and there are even more features that i haven't played with yet. they are SO worth the hype and the price tag. i am beyond satisfied with my purchase, and as a music lover, i think they're really going to improve my quality of life. i will never go back to any other earphone brand. thank you!

<Task Instructions> ========== Rely only on the context document, with no outside information. ---------- <Passage> ========== **AirPod Pro (2nd Gen) Customer Review** the sound quality and bass of these earphones are clear and exceptional for listening to both music and podcasts; it's like i'm hearing all of my favorite music again with new ears, including background harmonies and production qualities that i didn't notice before. they are so lightweight and comfortable, and i haven't had any issues with them falling out, which was a concern for me as someone who goes to the gym and wears glasses. they connected to my apple devices quickly and effortlessly, and they're very aesthetically beautiful and stylish in person. the noise cancellation feature is excellent and effectively blocks out background noise, sometimes so much so that i'm unaware of my surroundings, but the level of noise cancellation and volume can be adjusted based on your surroundings. there is also a feature where siri can read your notifications as they come in, which some people may find useful. you can answer, mute, unmute, and end calls by pressing them, and there are even more features that i haven't played with yet. they are SO worth the hype and the price tag. i am beyond satisfied with my purchase, and as a music lover, i think they're really going to improve my quality of life. i will never go back to any other earphone brand. thank you! ---------- <Question> ========== Based on the document, was the user satisfied with the product?

You must use the information provided in the prompt to answer any questions. Do not use any previous knowledge or additional information from any sources. Do not write more than 200 words for each response. If a list is included in the response, use bullet points, never numbers. When numbers are necessary in your response, write each one in text with the number in brackets after, for example, two (2) or twenty seven (27).

What are the pros and cons of each beta blocker?

Pharmacology of Intravenous β-Adrenergic Blockers propranolol Propranolol has an equal affinity for β1- and β2-receptors, lacks intrinsic sympathomimetic activity (ISA), and has no α-adrenergic receptor activity. It is the most lipidsoluble β-blocker and generally has the most central nervous system side effects. First-pass liver metabolism (90%) is very high, requiring much higher oral doses than intravenous doses for pharmacodynamic effect. The usual intravenous dose of propranolol initially is 0.5 to 1.0 mg titrated to effect. A titrated dose resulting in maximum pharmacologic serum levels is 0.1 mg/kg. The use of continuous infusions of propranolol has been reported after noncardiac surgery in patients with cardiac disease. A continuous infusion of 1 to 3 mg/hr can prevent tachycardia and hypertension but must be used cautiously because of the potential of cumulative effects. metoprolol Metoprolol was the first clinically used cardioselective β-blocker (Table 8-2). Its affinity for β1-receptors is 30 times higher than its affinity for β2-receptors, as demonstrated by radioligand binding. Metoprolol is lipid soluble, with 50% of the drug metabolized during first-pass hepatic metabolism and with only 3% BOX 8-3 Effects of β-Adrenergic Blockers on Myocardial Ischemia • Reductions in myocardial oxygen consumption • Improvements in coronary blood flow • Prolonged diastolic perfusion period • Improved collateral flow • Increased flow to ischemic areas • Overall improvement in supply/demand ratio • Stabilization of cellular membranes • Improved oxygen dissociation from hemoglobin • Inhibition of platelet aggregation • Reduced mortality after myocardial infarction BOX 8-4 Recommendations for Perioperative Medical Therapy • Class I β-Blockers required in the recent past to control symptoms of angina or symptomatic arrhythmias or hypertension; β-blockers: patients at high cardiac risk, owing to the finding of ischemia on preoperative testing, who are undergoing vascular surgery • Class IIa β-Blockers: preoperative assessment identifies untreated hypertension, known coronary disease, or major risk factors for coronary disease • Class III β-Blockers: contraindication to β-blockade Adapted from Eagle KA, Berger PB, Calkins H, et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery-executive summary: A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 39:542, 2002. iICARDIOVASCULAR PHYSIOLOGY, PHARMACOLOGY, AND MOLECULAR BIOLOGY 124 excreted renally. Protein binding is less than 10%. Metoprolol’s serum half-life is 3 to 4 hours. As with any cardioselective β-blocker, higher serum levels may result in greater incidence of β2-blocking effects. Metoprolol is administered intravenously in 1- to 2-mg doses, titrated to effect. The potency of metoprolol is approximately one half that of propranolol. Maximum β-blocker effect is achieved with 0.2 mg/kg given intravenously. esmolol Esmolol’s chemical structure is similar to that of metoprolol and propranolol, except it has a methylester group in the para position of the phenyl ring, making it susceptible to rapid hydrolysis by red blood cell esterases (9-minute half-life). Esmolol is not metabolized by plasma cholinesterase. Hydrolysis results in an acid metabolite and methanol with clinically insignificant levels. Ninety percent of the drug is eliminated in the form of the acid metabolite, normally within 24 hours. A loading dose of 500 μg/kg given intravenously, followed by a 50- to 300- μg/kg/min infusion, will reach steadystate concentrations within 5 minutes. Without the loading dose, steady-state concentrations are reached in 30 minutes. Esmolol is cardioselective, blocking primarily β1-receptors. It lacks ISA and membrane-stabilizing effects and is mildly lipid soluble. Esmolol produced significant reductions in BP, HR, and cardiac index after a loading dose of 500 μg/kg and an infusion of 300 μg/kg/min in patients with coronary artery disease, and the effects were completely reversed 30 minutes after discontinuation of the infusion. Initial therapy during anesthesia may require significant reductions in both the loading and infusion doses. Hypotension is a common side effect of intravenous esmolol. The incidence of hypotension was higher with esmolol (36%) than with propranolol (6%) at equal therapeutic endpoints. The cardioselective drugs may cause more hypotension because of β1-induced myocardial depression and the failure to block β2 peripheral vasodilation. Esmolol appears safe in patients with bronchospastic disease. In another comparative study with propranolol, esmolol and placebo did not change airway resistance whereas 50% of patients treated with propranolol developed clinically significant bronchospasm. labetalol Labetalol provides selective α1-receptor blockade and nonselective β1- and β2-blockade. The potency of β-adrenergic blockade is 5- to 10-fold greater than α1-adrenergic blockade. Labetalol has partial β2-agonist effects that promote vasodilation. Labetalol is moderately lipid soluble and is completely absorbed after oral administration. First-pass hepatic metabolism is significant with production of inactive metabolites. Renal excretion of the unchanged drug is minimal. Elimination half-life is approximately 6 hours. In contrast to other β-blockers, clinically, labetalol should be considered a peripheral vasodilator that does not cause a reflex tachycardia. BP and systolic vascular resistance decrease after an intravenous dose. Stroke volume (SV) and CO remain unchanged, with HR decreasing slightly. The reduction in BP is dose related, and acutely hypertensive patients usually respond within 3 to 5 minutes after a bolus dose of 100 to 250 μg/kg. However, the more critically ill or anesthetized patients should have their BP titrated beginning with 5- to 10-mg intravenous increments. Reduction in BP may last as long as 6 hours after intravenous dosing.

You must use the information provided in the prompt to answer any questions. Do not use any previous knowledge or additional information from any sources. Do not write more than 200 words for each response. If a list is included in the response, use bullet points, never numbers. When numbers are necessary in your response, write each one in text with the number in brackets after, for example, two (2) or twenty seven (27). Pharmacology of Intravenous β-Adrenergic Blockers propranolol Propranolol has an equal affinity for β1- and β2-receptors, lacks intrinsic sympathomimetic activity (ISA), and has no α-adrenergic receptor activity. It is the most lipidsoluble β-blocker and generally has the most central nervous system side effects. First-pass liver metabolism (90%) is very high, requiring much higher oral doses than intravenous doses for pharmacodynamic effect. The usual intravenous dose of propranolol initially is 0.5 to 1.0 mg titrated to effect. A titrated dose resulting in maximum pharmacologic serum levels is 0.1 mg/kg. The use of continuous infusions of propranolol has been reported after noncardiac surgery in patients with cardiac disease. A continuous infusion of 1 to 3 mg/hr can prevent tachycardia and hypertension but must be used cautiously because of the potential of cumulative effects. metoprolol Metoprolol was the first clinically used cardioselective β-blocker (Table 8-2). Its affinity for β1-receptors is 30 times higher than its affinity for β2-receptors, as demonstrated by radioligand binding. Metoprolol is lipid soluble, with 50% of the drug metabolized during first-pass hepatic metabolism and with only 3% BOX 8-3 Effects of β-Adrenergic Blockers on Myocardial Ischemia • Reductions in myocardial oxygen consumption • Improvements in coronary blood flow • Prolonged diastolic perfusion period • Improved collateral flow • Increased flow to ischemic areas • Overall improvement in supply/demand ratio • Stabilization of cellular membranes • Improved oxygen dissociation from hemoglobin • Inhibition of platelet aggregation • Reduced mortality after myocardial infarction BOX 8-4 Recommendations for Perioperative Medical Therapy • Class I β-Blockers required in the recent past to control symptoms of angina or symptomatic arrhythmias or hypertension; β-blockers: patients at high cardiac risk, owing to the finding of ischemia on preoperative testing, who are undergoing vascular surgery • Class IIa β-Blockers: preoperative assessment identifies untreated hypertension, known coronary disease, or major risk factors for coronary disease • Class III β-Blockers: contraindication to β-blockade Adapted from Eagle KA, Berger PB, Calkins H, et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery-executive summary: A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 39:542, 2002. iICARDIOVASCULAR PHYSIOLOGY, PHARMACOLOGY, AND MOLECULAR BIOLOGY 124 excreted renally. Protein binding is less than 10%. Metoprolol’s serum half-life is 3 to 4 hours. As with any cardioselective β-blocker, higher serum levels may result in greater incidence of β2-blocking effects. Metoprolol is administered intravenously in 1- to 2-mg doses, titrated to effect. The potency of metoprolol is approximately one half that of propranolol. Maximum β-blocker effect is achieved with 0.2 mg/kg given intravenously. esmolol Esmolol’s chemical structure is similar to that of metoprolol and propranolol, except it has a methylester group in the para position of the phenyl ring, making it susceptible to rapid hydrolysis by red blood cell esterases (9-minute half-life). Esmolol is not metabolized by plasma cholinesterase. Hydrolysis results in an acid metabolite and methanol with clinically insignificant levels. Ninety percent of the drug is eliminated in the form of the acid metabolite, normally within 24 hours. A loading dose of 500 μg/kg given intravenously, followed by a 50- to 300- μg/kg/min infusion, will reach steadystate concentrations within 5 minutes. Without the loading dose, steady-state concentrations are reached in 30 minutes. Esmolol is cardioselective, blocking primarily β1-receptors. It lacks ISA and membrane-stabilizing effects and is mildly lipid soluble. Esmolol produced significant reductions in BP, HR, and cardiac index after a loading dose of 500 μg/kg and an infusion of 300 μg/kg/min in patients with coronary artery disease, and the effects were completely reversed 30 minutes after discontinuation of the infusion. Initial therapy during anesthesia may require significant reductions in both the loading and infusion doses. Hypotension is a common side effect of intravenous esmolol. The incidence of hypotension was higher with esmolol (36%) than with propranolol (6%) at equal therapeutic endpoints. The cardioselective drugs may cause more hypotension because of β1-induced myocardial depression and the failure to block β2 peripheral vasodilation. Esmolol appears safe in patients with bronchospastic disease. In another comparative study with propranolol, esmolol and placebo did not change airway resistance whereas 50% of patients treated with propranolol developed clinically significant bronchospasm. labetalol Labetalol provides selective α1-receptor blockade and nonselective β1- and β2-blockade. The potency of β-adrenergic blockade is 5- to 10-fold greater than α1-adrenergic blockade. Labetalol has partial β2-agonist effects that promote vasodilation. Labetalol is moderately lipid soluble and is completely absorbed after oral administration. First-pass hepatic metabolism is significant with production of inactive metabolites. Renal excretion of the unchanged drug is minimal. Elimination half-life is approximately 6 hours. In contrast to other β-blockers, clinically, labetalol should be considered a peripheral vasodilator that does not cause a reflex tachycardia. BP and systolic vascular resistance decrease after an intravenous dose. Stroke volume (SV) and CO remain unchanged, with HR decreasing slightly. The reduction in BP is dose related, and acutely hypertensive patients usually respond within 3 to 5 minutes after a bolus dose of 100 to 250 μg/kg. However, the more critically ill or anesthetized patients should have their BP titrated beginning with 5- to 10-mg intravenous increments. Reduction in BP may last as long as 6 hours after intravenous dosing. What are the pros and cons of each beta blocker?

I'm providing you with your source material. You will not be using any outside material. Your job is to answer questions about the material.

What are the main takeaways?

Low Interest Rates: Causes and Consequences∗ Robert E. Hall Hoover Institution and Department of Economics, Stanford University National Bureau of Economic Research World interest rates have been declining for several decades. In a general equilibrium setting, the interest rate is determined by the interaction of a number of types of behavior: the policy of the central bank, investment in productive assets, the choice between current and future consumption, and the responses of wealth holders to risk. Central banks devote consider effort to determining equilibrium real rates, around which they set their policy rates, though measuring the equilibrium rate is challenging. The real interest rate is also connected to the marginal product of capital, though the connection is loose. Similarly, the real interest rate is connected to consumption growth through a Euler equation, but again many other influ- ences enter the relationship between the two variables. Finally, the idea of the “global saving glut” suggests that the rise of income in countries with high propensities to save may be a factor in the decline in real rates. That idea receives support in a simple model of global financial equilibrium between coun- tries with risk tolerance (the United States) and ones with high risk aversion (China). JEL Codes: E21, E22, E43, E52. Low world interest rates have stimulated new interest in the determination of the safe real rate. As a threshold matter, Rachel and Smith’s figure 1 (this issue) and Juselius et al.’s figure 1 (this issue) document the pronounced downward trend of world real inter- est rates since the 1980s. For the purposes of this commentary, I take ∗ This research was supported by the Hoover Institution. Complete backup for all of the calculations is available from my website, http://www.stanford. edu/∼rehall. Author contact: [email protected]; stanford.edu/∼rehall. 103 104 International Journal of Central Banking September 2017 the real rate to be the yield net of inflation of safe government debt of maturity around one to two years. Thus I abstract from liquidity effects at the short end of the yield curve and from issues related to the slope of the yield curve. Structural relations governing the real interest rate include its relation to • the central bank’s payment on reserves and the extent of sat- uration of the financial system in reserves • the marginal product of capital • the rate of consumption growth (through the Euler equation) • the terms of trade between risk-tolerant and risk-averse investors In a complete macro model one or more equations would describe each of these structural relations. It would not be possible to divide up responsibility among them for the overall decline in the real rate. One can fashion a set of highly simplified models, each containing only one or two of the structural relations. For example, Krugman (1998) considers an economy with no capital and no uncertainty to focus on monetary policy and consumption growth and illuminate issues of the zero lower bound. But a set of models along those lines would not result in an additive breakdown of the sources of the decline in the real interest rate. 1. Monetary Policy and the Real Interest Rate Traditional monetary policy kept the interest paid on reserves at zero nominal and manipulated the quantity of reserves. Explaining how the central bank influenced interest rates involved consideration of the liquidity value of scarce reserves. Today, all major central banks have saturated their financial systems with reserves, so the liquid- ity value is zero, and the central banks execute monetary policy exclusively by manipulation of the payment made to reserve hold- ers (in the United States, a new kind of reserves, reverse repurchase agreements, play this role). Powerful forces of arbitrage link the central bank’s policy rate paid on reserves to similar short-term government obligations. The Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 105 central bank thus controls short rates directly. But the fact of central bank control does not mean that we need look no further to under- stand the movements of short rates. For one thing, it is the behavior of real rates that matters and all central banks set nominal rates, though there would be no obstacle to direct setting of real rates. Hall and Reis (2016) discusses these topics in detail. Thus the behavior of inflation needs to be brought into the picture. More important, however, is that changing the policy rate has effects on output and employment relatively quickly and on inflation, with a longer lag, according to most views. As a result of the influence of the central bank’s policy rate on the other key macro variables, the other structural relations listed above come into play in the central bank’s choice of the policy rate. Only the most naive observer thinks that the central bank can pick its policy rate by unilateral whim. Friedman (1968), following Wick- sell, set forth a framework that remains influential fifty years later: There is a level of the real interest rate, r∗ , the natural rate, with the property that it is infeasible for the central bank to run a mon- etary policy that results in a real rate permanently above or below the natural rate. Thus many discussions of the behavior of the real rate focus on quantifying r∗ , generally as a quantity that varies over time. Since 1980, it has had a downward trend. The foundations of the hypothesis that rt∗ is a cognizable fea- ture of the economy are weak, in my opinion—see Hall (2005). It takes an economic or statistical model to extract rt∗ from data on rt and other variables. The results are model specific. Laubach and Williams (2003) is the canon of this literature. Notwithstand- ing my doubts about the foundations, these authors’ results seem completely reasonable. Juselius et al. (this issue) refine the canon. The middle of their figure 6 shows the real rate, which is volatile and cyclical. The Laubach-Williams natural rate is a plausibly smoothed version of the actual real rate. As Friedman’s analysis predicted, the actual real rate exceeds its natural level in booms and falls below in busts. The natural rate of Juselius et al. has higher volatility and, surprisingly, a higher level. Friedman’s analysis suggested fairly per- suasively that the real rate should deviate above about as much as below the natural rate, but the new construction has almost all of the deviations below. 106 International Journal of Central Banking September 2017 Figure 1. Spread between the Return to Capital and the Safe Real Interest Rate 2. The Marginal Product of Capital and the Return to Capital In an economy without uncertainty, the return to capital is linked to the marginal product by the rental price of capital. Provided the rental price includes the fluctuations in Tobin’s q—the ratio of the value of installed capital to the acquisition price of capital— arbitrage should equate the marginal product of capital to the rental price. To put it differently, if the rate of return is calculated from data that accounts for q, the rate of return will track the inter- est rate (measured over the same interval) period by period. With uncertainty, the rate of return will include a risk premium, which may vary over time. The recent macro literature has studied finan- cial frictions that interpose between wealth holders and businesses seeking to attract wealth to form business capital. Figure 1 shows the spread between the calculated return to cap- ital and the one-year safe real interest rate, from Hall (2015). Note that the spread is remarkably volatile, upward trending, and high except in recessions. Gomme, Ravikumar, and Rupert (2015) have made similar calculations. The notion that there is a tight connec- tion between the safe interest rate and the return to capital receives Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 107 Figure 2. U.S. Real Rate and Consumption Growth little support from this evidence. Rather, there is apparently large scope for variations over time in risk premiums, financial frictions, and other sources of the wedge between the earnings of capital and the risk-free cost of borrowing. These variations are almost certainly endogenous. 3. Consumption Growth and the Interest Rate Many macro models, including the New Keynesian models that have proliferated at central banks, contain an upward-sloping structural relation between expected consumption growth and the real interest rate—Rachel and Smith’s equation (1) describes the Euler equation reflecting this relation. The logic is that a higher real interest rate makes future consumption cheaper than current consumption, so households consume less currently and more in the future. To put it another way, higher growth rates should have correspondingly higher real interest rates. Figure 2 shows that this proposition is somewhat true in U.S. data averaged over decades. The proposition encounters some serious obstacles. First, Carroll and Summers (1991) observed that across countries that can trade goods and financial claims, all countries should have the same rate of growth of consumption, in accord with the worldwide real interest 108 International Journal of Central Banking September 2017 rate, irrespective of their rates of growth of income. Countries with high expected income growth should borrow from slower-growing countries and gradually pay the debt off as growth occurs. In fact, the evidence shows that consumption growth is tightly linked to income growth across countries. And growth rates differ markedly across countries, with the highest growth in recent decades in east and south Asia. Second, a household does not have a single Euler equation, but rather a different one for each asset. Hansen and Singleton (1983) is the classic citation on this point. There is nothing special about the safe real interest rate. Their paper showed that the data rejected the hypothesis that households satisfied all of the Euler equations. Third, data on household financial holdings make it clear that households with collectively an important fraction of total income face binding constraints on borrowing. They would like to obey the Euler-equation model but cannot commit to repaying the debt that they would incur if they did. They obey a related model where a shadow borrowing rate, higher than the measured one, tracks con- sumption growth. I conclude that research on consumption choices has a far richer view than the one expressed in the simple interest-only Euler equation. 4. The Role of the Interest Rate in an Economy where Risk-Tolerant Investors Insure Risk-Averse Ones by Borrowing from Them Hall (2016) demonstrates the theoretical and practical importance of trade among heterogeneous investors. In effect, the risk-tolerant investors insure the risk-averse ones. Debt has a key role in this risk- motivated trade. By borrowing from the risk averse, the risk-tolerant investors provide the risk averse with protection against future ran- dom shocks, because the payoff of the debt is unaffected by the shocks (provided no default occurs). The interest rate on the debt describes the terms of the risk trade. If the risk tolerant have high resources relative to the risk averse, collectively, the risk averse com- mand a good deal—they receive a high rate of interest on the funds they loan to the risk tolerant. But if there is an upward trend in the resources of the risk averse, the deal shifts disadvantageously away Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 109 from the risk averse—they earn less and less interest on the funds they lend. The paper shows that China behaves risk aversely, lending large volumes of funds to western Europe and the United States. But the Chinese resource base—measured by GDP—is growing faster than the resource base of the risk-tolerant borrowers. Hence the world real interest rate is declining on account of the differential growth. The model backing up this analysis is rigged to avoid the other issues discussed earlier in this commentary. There is no central bank intervening in the world financial market. There is no capital, so no issue of the relation of the marginal product of capital to the interest rate. Resources are growing at the rate of zero among the risk averse and the risk tolerant, so there are no issues of growth affecting the interest rate. The model embodies standard ideas from financial markets, including the hypothesis that investors attribute a small but positive probability that a truly bad event will occur and the hypothesis that the risk-averse investors place a somewhat higher probability on that event. My paper pursues the ideas in Bernanke et al. (2011) that there is a “global savings glut” and in Gourinchas, Rey, and Govillot (2010) and Caballero and Farhi (2016) that low real interest rates are the result of a “shortage” of safe assets. The paper derives results along those lines from the equilibrium of an Arrow-Debreu economy with complete capital markets. In place of gluts and shortages, the model hypothesizes changes over time in the resources held by the risk tolerant in relation to those held by the risk averse. Figure 3 shows how the safe real interest rate in the model declines as the fraction of resources held by the risk tolerant declines. The decline is similar to the decline that actually occurred from 1990 to the present, with real rates at or below zero. The risk-tolerant investors in the model have modestly lower coefficients of relative risk aversion and believe that the probability of bad conditions is modestly lower, compared with the risk-averse investors. The conclusion of the model is that heterogeneity coupled with a shift in relative resources toward the risk-averse investors can explain observed changes in the real interest rate without bringing in the declining growth rate or rising financial frictions. The paper makes no claim that the other forces are not actually influential, however. Fundamental to the success of the model is its hypothesis that both 110 International Journal of Central Banking September 2017 Figure 3. As the Fraction of Resources in the Hands of the Risk Tolerant Declines, the Interest Rate Falls types of investors behave as if they assigned small but important probabilities to a substantial negative shock, worse than has actu- ally occurred since the Great Depression. In this respect, the model follows the trend in recent financial economics, which finds, for exam- ple, that such beliefs about rare disasters are the most plausible way to explain the equity premium. One of the manifestations of heterogeneity in investors’ risk aver- sion is across countries. Investors in some countries, notably the United States, collectively take on risk from other parts of the world by maintaining positive net positions in foreign equity and negative net positions in debt—in effect, these countries borrow from the risk- averse countries and use the proceeds to buy foreign equity. Thus the United States is like a leveraged hedge fund. Countries can be divided into three groups: (i) those that absorb risk by borrowing in the global debt market and buying foreign equity, (ii) those that shed risk by lending to the risk absorbers and letting those countries take on the risk of their own equity, and (iii) those whose risk preferences are in the middle and choose not to absorb or shed risk and those whose financial markets are undeveloped and do not participate in global financial markets. Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 111 Figure 4. Countries that Absorb Risk by Holding Positive Amounts of Net Foreign Equity or by Borrowing from Foreign Lenders Note: Risk-absorbing countries are shown by dark shading. Created with mapchart.net. Figure 4 shows the countries that absorb risk. They are the advanced countries of western Europe and the countries scattered around the globe that fell under the influence of those countries and became advanced themselves. There appears to be a negative cor- relation between risk aversion and income per person, as the risk absorbers are all high-income countries. By far the largest absorber of risk is the United States. Figure 5 shows the countries that shed risk. Most are lower income. China is by far the largest of the shedders. China holds large amounts of dollar debt claims on the United States, with recent growth in its euro debt claims on western Europe. One high-income country, Japan, is a major risk shedder. The United States and other risk absorbers hold positive net amounts of foreign equity. Figure 6 shows the growth of risk absorption by the United States. The upper line shows U.S. net borrowing in the debt market and the lower line net U.S. holdings of foreign equity. The upward path in debt began in the mid-1980s and the upward path of equity in the 1990s. Debt continued to rise through 2011 (the last year for which I have data) while equity fell slightly after the 2008 financial 112 International Journal of Central Banking September 2017 Figure 5. Countries that Shed Risk by Holding Negative Amounts of Net Foreign Equity or by Lending Positive Amounts to Foreign Borrowers Note: Risk-shedding countries are shown by dark shading. Created with mapchart.net. Figure 6. Risk Absorption by the United States, 1970–2011 Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 113 Figure 7. Risk Shedding by China, 1981–2011 crisis. The average of the two measures—taken as an overall measure of risk absorption—rose from the 1980s and reached a plateau of 0.3 years of GDP. Figure 7 shows similar data for China starting in 1981—in ear- lier years, China was effectively walled off from the global economy. Starting in the early 1990s, China shed risk aggressively, reaching the point just before the crisis of the average of foreign debt owned and net foreign holdings of Chinese equity claims equal to 0.4 years of GDP. Following the crisis, Chinese risk shedding has remained at that level but has not grown. Risk splitting occurs within the United States in large volumes as well. Table 1 shows decade averages of a variety of financial institutions that hold risky financial positions funded in part by debt—held by risk-averse investors such as pension funds—and by correspondingly riskier equity held by risk-tolerant investors such as high-wealth households. Government debt is a prominent part of the risk splitting. In the case of government, the taxpayers make up the risk-tolerant side—the marginal taxpayer with substantially higher than average wealth takes on magnified risk by insuring the holders of government debt. On the private side, numerous types of financial institutions and securities have the effect of splitting risk between a tranche of low-risk debt and high-risk residual equity claims.  114 Table 1. Examples of the Scale of Risk-Splitting Institutions Government Private Consolidated GSE Private Non-mortgage Government GSE Guaranteed Equity Securiti- Non-financial Household Decade Debt Debt Debt Funds zations Corporate Debt Repos Debt 1980s 0.469 0.061 0.091 — 0.012 0.163 0.103 0.186 1990s 0.611 0.101 0.204 — 0.086 0.211 0.166 0.204 2000s 0.574 0.203 0.293 0.058 0.233 0.238 0.237 0.239 2010s 0.936 0.126 0.347 0.140 0.109 0.275 0.221 0.251 International Journal of Central Banking September 2017 Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 115 Figure 8. Scale of Risk-Splitting Institutions Relative to GDP Private equity is a rapidly growing example of this type of financial arrangement. Securitizations with overcollateralized debtlike securi- ties held by or on behalf of risk-averse investors and residual equity claims held by risk-tolerant investors grew rapidly until the crisis but have shrunk since then. Repurchase agreements split risk by overcollateralization to the extent of the repo haircut. These too have shrunk relative to GDP since the crisis. Figure 8 shows the generally upward trend of the volume of risk splitting in the United States, stated relative to GDP. Both gov- ernment and non-government contributions have risen, with some moderation after the crisis. 5. Concluding Remarks Prior to the financial crisis in 2008, risk splitting grew steadily, as revealed in data on both international and domestic financial posi- tions. Safe real interest rates declined in parallel. The crisis resulted in a downward jump in real rates corresponding to the fall in nom- inal short rates to essentially zero soon after the crisis struck. The corresponding real rate was between –1 percent and –2 percent. Real rates have risen in the United States recently, as nominal rates have 116 International Journal of Central Banking September 2017 become positive and inflation has risen close to the Federal Reserve’s target of 2 percent, but real rates in other markets remain as nega- tive as ever in the eight years since the crisis. Because the crisis hit GDP and asset value harder in advanced countries than in others, especially China, the influence studied in my analysis may explain some part of the drop in the global safe real short rate. In addition, the crisis may have raised investors’ beliefs about the probability of adverse events in the future, as in Kozlowski, Veldkamp, and Venkateswaran (2015). According to the principles considered here, the safe real rate would fall if the disaster probability rose more for the risk-averse investors than for the risk tolerant. I emphasize again that heterogeneity in risk aversion is only one of the factors entering a full explanation of the behavior of real rates over recent decades. Expansionary monetary policy, rising financial frictions, and slowing consumption growth need to be brought into a full analysis. References Bernanke, B. S., C. Bertaut, L. Pounder DeMarco, and S. Kamin. 2011. “International Capital Flows and the Returns to Safe Assets in the United States, 2003–2007.” International Finance Discussion Paper No. 1014, Board of Governors of the Federal Reserve System (February). Caballero, R. J., and E. Farhi. 2016. “The Safety Trap.” March. Harvard University, Department of Economics. Carroll, C. D., and L. H. Summers. 1991. “Consumption Growth Parallels Income Growth: Some New Evidence.” In National Sav- ing and Economic Performance, ed. B. D. Bernheim and J. B. Shovin, 305–48 (chapter 10). University of Chicago Press. Friedman, M. 1968. “The Role of Monetary Policy.” Presidential address delivered at the 80th Annual Meeting of the American Economics Association, Washington, DC, December 29, 1967. American Economic Review 58 (1): 1–15. Gomme, P., B. Ravikumar, and P. Rupert. 2015. “Secular Stagnation and Returns on Capital.” Economic Synopses (Federal Reserve Bank of St. Louis) (19): 1–3. Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 117 Gourinchas, P.-O., H. Rey, and N. Govillot. 2010. “Exorbitant Priv- ilege and Exorbitant Duty.” Discussion Paper No. 10-E-20, Insti- tute for Monetary and Economic Studies, Bank of Japan. Hall, R. E. 2005. “Separating the Business Cycle from Other Eco- nomic Fluctuations.” In The Greenspan Era: Lessons for the Future, 133–79. Proceedings of a symposium sponsored by the Federal Reserve Bank of Kansas City, August 25–27. ———. 2015. “Quantifying the Lasting Harm to the U.S. Economy from the Financial Crisis.” NBER Macroeconomics Annual 2014, Vol. 29, ed. J. A. Parker and M. Woodford, 71–128. University of Chicago Press. ———. 2016. “The Role of the Growth of Risk-Averse Wealth in the Decline of the Safe Real Interest Rate.” Hoover Institution (November). Hall, R. E., and R. Reis. 2016. “Achieving Price Stability by Manipu- lating the Central Bank’s Payment on Reserves.” NBER Working Paper No. 22761 (October). Hansen, L. P., and K. J. Singleton. 1983. “Stochastic Consumption, Risk Aversion, and the Temporal Behavior of Asset Returns.” Journal of Political Economy 91 (2): 249–65. Kozlowski, J., L. Veldkamp, and V. Venkateswaran. 2015. “The Tail that Wags the Economy: Beliefs and Persistent Stagnation.” NBER Working Paper No. 21719 (November). Krugman, P. R. 1998. “It’s Baaack: Japan’s Slump and the Return of the Liquidity Trap.” Brookings Papers on Economic Activity (2): 137–205. Laubach, T., and J. C Williams. 2003. “Measuring the Natural Rate of Interest.” Review of Economics and Statistics 85 (4): 1063–70. 

I'm providing you with your source material. You will not be using any outside material. Your job is to answer questions about the material. What are the main takeaways? Low Interest Rates: Causes and Consequences∗ Robert E. Hall Hoover Institution and Department of Economics, Stanford University National Bureau of Economic Research World interest rates have been declining for several decades. In a general equilibrium setting, the interest rate is determined by the interaction of a number of types of behavior: the policy of the central bank, investment in productive assets, the choice between current and future consumption, and the responses of wealth holders to risk. Central banks devote consider effort to determining equilibrium real rates, around which they set their policy rates, though measuring the equilibrium rate is challenging. The real interest rate is also connected to the marginal product of capital, though the connection is loose. Similarly, the real interest rate is connected to consumption growth through a Euler equation, but again many other influ- ences enter the relationship between the two variables. Finally, the idea of the “global saving glut” suggests that the rise of income in countries with high propensities to save may be a factor in the decline in real rates. That idea receives support in a simple model of global financial equilibrium between coun- tries with risk tolerance (the United States) and ones with high risk aversion (China). JEL Codes: E21, E22, E43, E52. Low world interest rates have stimulated new interest in the determination of the safe real rate. As a threshold matter, Rachel and Smith’s figure 1 (this issue) and Juselius et al.’s figure 1 (this issue) document the pronounced downward trend of world real inter- est rates since the 1980s. For the purposes of this commentary, I take ∗ This research was supported by the Hoover Institution. Complete backup for all of the calculations is available from my website, http://www.stanford. edu/∼rehall. Author contact: [email protected]; stanford.edu/∼rehall. 103 104 International Journal of Central Banking September 2017 the real rate to be the yield net of inflation of safe government debt of maturity around one to two years. Thus I abstract from liquidity effects at the short end of the yield curve and from issues related to the slope of the yield curve. Structural relations governing the real interest rate include its relation to • the central bank’s payment on reserves and the extent of sat- uration of the financial system in reserves • the marginal product of capital • the rate of consumption growth (through the Euler equation) • the terms of trade between risk-tolerant and risk-averse investors In a complete macro model one or more equations would describe each of these structural relations. It would not be possible to divide up responsibility among them for the overall decline in the real rate. One can fashion a set of highly simplified models, each containing only one or two of the structural relations. For example, Krugman (1998) considers an economy with no capital and no uncertainty to focus on monetary policy and consumption growth and illuminate issues of the zero lower bound. But a set of models along those lines would not result in an additive breakdown of the sources of the decline in the real interest rate. 1. Monetary Policy and the Real Interest Rate Traditional monetary policy kept the interest paid on reserves at zero nominal and manipulated the quantity of reserves. Explaining how the central bank influenced interest rates involved consideration of the liquidity value of scarce reserves. Today, all major central banks have saturated their financial systems with reserves, so the liquid- ity value is zero, and the central banks execute monetary policy exclusively by manipulation of the payment made to reserve hold- ers (in the United States, a new kind of reserves, reverse repurchase agreements, play this role). Powerful forces of arbitrage link the central bank’s policy rate paid on reserves to similar short-term government obligations. The Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 105 central bank thus controls short rates directly. But the fact of central bank control does not mean that we need look no further to under- stand the movements of short rates. For one thing, it is the behavior of real rates that matters and all central banks set nominal rates, though there would be no obstacle to direct setting of real rates. Hall and Reis (2016) discusses these topics in detail. Thus the behavior of inflation needs to be brought into the picture. More important, however, is that changing the policy rate has effects on output and employment relatively quickly and on inflation, with a longer lag, according to most views. As a result of the influence of the central bank’s policy rate on the other key macro variables, the other structural relations listed above come into play in the central bank’s choice of the policy rate. Only the most naive observer thinks that the central bank can pick its policy rate by unilateral whim. Friedman (1968), following Wick- sell, set forth a framework that remains influential fifty years later: There is a level of the real interest rate, r∗ , the natural rate, with the property that it is infeasible for the central bank to run a mon- etary policy that results in a real rate permanently above or below the natural rate. Thus many discussions of the behavior of the real rate focus on quantifying r∗ , generally as a quantity that varies over time. Since 1980, it has had a downward trend. The foundations of the hypothesis that rt∗ is a cognizable fea- ture of the economy are weak, in my opinion—see Hall (2005). It takes an economic or statistical model to extract rt∗ from data on rt and other variables. The results are model specific. Laubach and Williams (2003) is the canon of this literature. Notwithstand- ing my doubts about the foundations, these authors’ results seem completely reasonable. Juselius et al. (this issue) refine the canon. The middle of their figure 6 shows the real rate, which is volatile and cyclical. The Laubach-Williams natural rate is a plausibly smoothed version of the actual real rate. As Friedman’s analysis predicted, the actual real rate exceeds its natural level in booms and falls below in busts. The natural rate of Juselius et al. has higher volatility and, surprisingly, a higher level. Friedman’s analysis suggested fairly per- suasively that the real rate should deviate above about as much as below the natural rate, but the new construction has almost all of the deviations below. 106 International Journal of Central Banking September 2017 Figure 1. Spread between the Return to Capital and the Safe Real Interest Rate 2. The Marginal Product of Capital and the Return to Capital In an economy without uncertainty, the return to capital is linked to the marginal product by the rental price of capital. Provided the rental price includes the fluctuations in Tobin’s q—the ratio of the value of installed capital to the acquisition price of capital— arbitrage should equate the marginal product of capital to the rental price. To put it differently, if the rate of return is calculated from data that accounts for q, the rate of return will track the inter- est rate (measured over the same interval) period by period. With uncertainty, the rate of return will include a risk premium, which may vary over time. The recent macro literature has studied finan- cial frictions that interpose between wealth holders and businesses seeking to attract wealth to form business capital. Figure 1 shows the spread between the calculated return to cap- ital and the one-year safe real interest rate, from Hall (2015). Note that the spread is remarkably volatile, upward trending, and high except in recessions. Gomme, Ravikumar, and Rupert (2015) have made similar calculations. The notion that there is a tight connec- tion between the safe interest rate and the return to capital receives Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 107 Figure 2. U.S. Real Rate and Consumption Growth little support from this evidence. Rather, there is apparently large scope for variations over time in risk premiums, financial frictions, and other sources of the wedge between the earnings of capital and the risk-free cost of borrowing. These variations are almost certainly endogenous. 3. Consumption Growth and the Interest Rate Many macro models, including the New Keynesian models that have proliferated at central banks, contain an upward-sloping structural relation between expected consumption growth and the real interest rate—Rachel and Smith’s equation (1) describes the Euler equation reflecting this relation. The logic is that a higher real interest rate makes future consumption cheaper than current consumption, so households consume less currently and more in the future. To put it another way, higher growth rates should have correspondingly higher real interest rates. Figure 2 shows that this proposition is somewhat true in U.S. data averaged over decades. The proposition encounters some serious obstacles. First, Carroll and Summers (1991) observed that across countries that can trade goods and financial claims, all countries should have the same rate of growth of consumption, in accord with the worldwide real interest 108 International Journal of Central Banking September 2017 rate, irrespective of their rates of growth of income. Countries with high expected income growth should borrow from slower-growing countries and gradually pay the debt off as growth occurs. In fact, the evidence shows that consumption growth is tightly linked to income growth across countries. And growth rates differ markedly across countries, with the highest growth in recent decades in east and south Asia. Second, a household does not have a single Euler equation, but rather a different one for each asset. Hansen and Singleton (1983) is the classic citation on this point. There is nothing special about the safe real interest rate. Their paper showed that the data rejected the hypothesis that households satisfied all of the Euler equations. Third, data on household financial holdings make it clear that households with collectively an important fraction of total income face binding constraints on borrowing. They would like to obey the Euler-equation model but cannot commit to repaying the debt that they would incur if they did. They obey a related model where a shadow borrowing rate, higher than the measured one, tracks con- sumption growth. I conclude that research on consumption choices has a far richer view than the one expressed in the simple interest-only Euler equation. 4. The Role of the Interest Rate in an Economy where Risk-Tolerant Investors Insure Risk-Averse Ones by Borrowing from Them Hall (2016) demonstrates the theoretical and practical importance of trade among heterogeneous investors. In effect, the risk-tolerant investors insure the risk-averse ones. Debt has a key role in this risk- motivated trade. By borrowing from the risk averse, the risk-tolerant investors provide the risk averse with protection against future ran- dom shocks, because the payoff of the debt is unaffected by the shocks (provided no default occurs). The interest rate on the debt describes the terms of the risk trade. If the risk tolerant have high resources relative to the risk averse, collectively, the risk averse com- mand a good deal—they receive a high rate of interest on the funds they loan to the risk tolerant. But if there is an upward trend in the resources of the risk averse, the deal shifts disadvantageously away Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 109 from the risk averse—they earn less and less interest on the funds they lend. The paper shows that China behaves risk aversely, lending large volumes of funds to western Europe and the United States. But the Chinese resource base—measured by GDP—is growing faster than the resource base of the risk-tolerant borrowers. Hence the world real interest rate is declining on account of the differential growth. The model backing up this analysis is rigged to avoid the other issues discussed earlier in this commentary. There is no central bank intervening in the world financial market. There is no capital, so no issue of the relation of the marginal product of capital to the interest rate. Resources are growing at the rate of zero among the risk averse and the risk tolerant, so there are no issues of growth affecting the interest rate. The model embodies standard ideas from financial markets, including the hypothesis that investors attribute a small but positive probability that a truly bad event will occur and the hypothesis that the risk-averse investors place a somewhat higher probability on that event. My paper pursues the ideas in Bernanke et al. (2011) that there is a “global savings glut” and in Gourinchas, Rey, and Govillot (2010) and Caballero and Farhi (2016) that low real interest rates are the result of a “shortage” of safe assets. The paper derives results along those lines from the equilibrium of an Arrow-Debreu economy with complete capital markets. In place of gluts and shortages, the model hypothesizes changes over time in the resources held by the risk tolerant in relation to those held by the risk averse. Figure 3 shows how the safe real interest rate in the model declines as the fraction of resources held by the risk tolerant declines. The decline is similar to the decline that actually occurred from 1990 to the present, with real rates at or below zero. The risk-tolerant investors in the model have modestly lower coefficients of relative risk aversion and believe that the probability of bad conditions is modestly lower, compared with the risk-averse investors. The conclusion of the model is that heterogeneity coupled with a shift in relative resources toward the risk-averse investors can explain observed changes in the real interest rate without bringing in the declining growth rate or rising financial frictions. The paper makes no claim that the other forces are not actually influential, however. Fundamental to the success of the model is its hypothesis that both 110 International Journal of Central Banking September 2017 Figure 3. As the Fraction of Resources in the Hands of the Risk Tolerant Declines, the Interest Rate Falls types of investors behave as if they assigned small but important probabilities to a substantial negative shock, worse than has actu- ally occurred since the Great Depression. In this respect, the model follows the trend in recent financial economics, which finds, for exam- ple, that such beliefs about rare disasters are the most plausible way to explain the equity premium. One of the manifestations of heterogeneity in investors’ risk aver- sion is across countries. Investors in some countries, notably the United States, collectively take on risk from other parts of the world by maintaining positive net positions in foreign equity and negative net positions in debt—in effect, these countries borrow from the risk- averse countries and use the proceeds to buy foreign equity. Thus the United States is like a leveraged hedge fund. Countries can be divided into three groups: (i) those that absorb risk by borrowing in the global debt market and buying foreign equity, (ii) those that shed risk by lending to the risk absorbers and letting those countries take on the risk of their own equity, and (iii) those whose risk preferences are in the middle and choose not to absorb or shed risk and those whose financial markets are undeveloped and do not participate in global financial markets. Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 111 Figure 4. Countries that Absorb Risk by Holding Positive Amounts of Net Foreign Equity or by Borrowing from Foreign Lenders Note: Risk-absorbing countries are shown by dark shading. Created with mapchart.net. Figure 4 shows the countries that absorb risk. They are the advanced countries of western Europe and the countries scattered around the globe that fell under the influence of those countries and became advanced themselves. There appears to be a negative cor- relation between risk aversion and income per person, as the risk absorbers are all high-income countries. By far the largest absorber of risk is the United States. Figure 5 shows the countries that shed risk. Most are lower income. China is by far the largest of the shedders. China holds large amounts of dollar debt claims on the United States, with recent growth in its euro debt claims on western Europe. One high-income country, Japan, is a major risk shedder. The United States and other risk absorbers hold positive net amounts of foreign equity. Figure 6 shows the growth of risk absorption by the United States. The upper line shows U.S. net borrowing in the debt market and the lower line net U.S. holdings of foreign equity. The upward path in debt began in the mid-1980s and the upward path of equity in the 1990s. Debt continued to rise through 2011 (the last year for which I have data) while equity fell slightly after the 2008 financial 112 International Journal of Central Banking September 2017 Figure 5. Countries that Shed Risk by Holding Negative Amounts of Net Foreign Equity or by Lending Positive Amounts to Foreign Borrowers Note: Risk-shedding countries are shown by dark shading. Created with mapchart.net. Figure 6. Risk Absorption by the United States, 1970–2011 Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 113 Figure 7. Risk Shedding by China, 1981–2011 crisis. The average of the two measures—taken as an overall measure of risk absorption—rose from the 1980s and reached a plateau of 0.3 years of GDP. Figure 7 shows similar data for China starting in 1981—in ear- lier years, China was effectively walled off from the global economy. Starting in the early 1990s, China shed risk aggressively, reaching the point just before the crisis of the average of foreign debt owned and net foreign holdings of Chinese equity claims equal to 0.4 years of GDP. Following the crisis, Chinese risk shedding has remained at that level but has not grown. Risk splitting occurs within the United States in large volumes as well. Table 1 shows decade averages of a variety of financial institutions that hold risky financial positions funded in part by debt—held by risk-averse investors such as pension funds—and by correspondingly riskier equity held by risk-tolerant investors such as high-wealth households. Government debt is a prominent part of the risk splitting. In the case of government, the taxpayers make up the risk-tolerant side—the marginal taxpayer with substantially higher than average wealth takes on magnified risk by insuring the holders of government debt. On the private side, numerous types of financial institutions and securities have the effect of splitting risk between a tranche of low-risk debt and high-risk residual equity claims.  114 Table 1. Examples of the Scale of Risk-Splitting Institutions Government Private Consolidated GSE Private Non-mortgage Government GSE Guaranteed Equity Securiti- Non-financial Household Decade Debt Debt Debt Funds zations Corporate Debt Repos Debt 1980s 0.469 0.061 0.091 — 0.012 0.163 0.103 0.186 1990s 0.611 0.101 0.204 — 0.086 0.211 0.166 0.204 2000s 0.574 0.203 0.293 0.058 0.233 0.238 0.237 0.239 2010s 0.936 0.126 0.347 0.140 0.109 0.275 0.221 0.251 International Journal of Central Banking September 2017 Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 115 Figure 8. Scale of Risk-Splitting Institutions Relative to GDP Private equity is a rapidly growing example of this type of financial arrangement. Securitizations with overcollateralized debtlike securi- ties held by or on behalf of risk-averse investors and residual equity claims held by risk-tolerant investors grew rapidly until the crisis but have shrunk since then. Repurchase agreements split risk by overcollateralization to the extent of the repo haircut. These too have shrunk relative to GDP since the crisis. Figure 8 shows the generally upward trend of the volume of risk splitting in the United States, stated relative to GDP. Both gov- ernment and non-government contributions have risen, with some moderation after the crisis. 5. Concluding Remarks Prior to the financial crisis in 2008, risk splitting grew steadily, as revealed in data on both international and domestic financial posi- tions. Safe real interest rates declined in parallel. The crisis resulted in a downward jump in real rates corresponding to the fall in nom- inal short rates to essentially zero soon after the crisis struck. The corresponding real rate was between –1 percent and –2 percent. Real rates have risen in the United States recently, as nominal rates have 116 International Journal of Central Banking September 2017 become positive and inflation has risen close to the Federal Reserve’s target of 2 percent, but real rates in other markets remain as nega- tive as ever in the eight years since the crisis. Because the crisis hit GDP and asset value harder in advanced countries than in others, especially China, the influence studied in my analysis may explain some part of the drop in the global safe real short rate. In addition, the crisis may have raised investors’ beliefs about the probability of adverse events in the future, as in Kozlowski, Veldkamp, and Venkateswaran (2015). According to the principles considered here, the safe real rate would fall if the disaster probability rose more for the risk-averse investors than for the risk tolerant. I emphasize again that heterogeneity in risk aversion is only one of the factors entering a full explanation of the behavior of real rates over recent decades. Expansionary monetary policy, rising financial frictions, and slowing consumption growth need to be brought into a full analysis. References Bernanke, B. S., C. Bertaut, L. Pounder DeMarco, and S. Kamin. 2011. “International Capital Flows and the Returns to Safe Assets in the United States, 2003–2007.” International Finance Discussion Paper No. 1014, Board of Governors of the Federal Reserve System (February). Caballero, R. J., and E. Farhi. 2016. “The Safety Trap.” March. Harvard University, Department of Economics. Carroll, C. D., and L. H. Summers. 1991. “Consumption Growth Parallels Income Growth: Some New Evidence.” In National Sav- ing and Economic Performance, ed. B. D. Bernheim and J. B. Shovin, 305–48 (chapter 10). University of Chicago Press. Friedman, M. 1968. “The Role of Monetary Policy.” Presidential address delivered at the 80th Annual Meeting of the American Economics Association, Washington, DC, December 29, 1967. American Economic Review 58 (1): 1–15. Gomme, P., B. Ravikumar, and P. Rupert. 2015. “Secular Stagnation and Returns on Capital.” Economic Synopses (Federal Reserve Bank of St. Louis) (19): 1–3. Vol. 13 No. 3 Low Interest Rates: Causes and Consequences 117 Gourinchas, P.-O., H. Rey, and N. Govillot. 2010. “Exorbitant Priv- ilege and Exorbitant Duty.” Discussion Paper No. 10-E-20, Insti- tute for Monetary and Economic Studies, Bank of Japan. Hall, R. E. 2005. “Separating the Business Cycle from Other Eco- nomic Fluctuations.” In The Greenspan Era: Lessons for the Future, 133–79. Proceedings of a symposium sponsored by the Federal Reserve Bank of Kansas City, August 25–27. ———. 2015. “Quantifying the Lasting Harm to the U.S. Economy from the Financial Crisis.” NBER Macroeconomics Annual 2014, Vol. 29, ed. J. A. Parker and M. Woodford, 71–128. University of Chicago Press. ———. 2016. “The Role of the Growth of Risk-Averse Wealth in the Decline of the Safe Real Interest Rate.” Hoover Institution (November). Hall, R. E., and R. Reis. 2016. “Achieving Price Stability by Manipu- lating the Central Bank’s Payment on Reserves.” NBER Working Paper No. 22761 (October). Hansen, L. P., and K. J. Singleton. 1983. “Stochastic Consumption, Risk Aversion, and the Temporal Behavior of Asset Returns.” Journal of Political Economy 91 (2): 249–65. Kozlowski, J., L. Veldkamp, and V. Venkateswaran. 2015. “The Tail that Wags the Economy: Beliefs and Persistent Stagnation.” NBER Working Paper No. 21719 (November). Krugman, P. R. 1998. “It’s Baaack: Japan’s Slump and the Return of the Liquidity Trap.” Brookings Papers on Economic Activity (2): 137–205. Laubach, T., and J. C Williams. 2003. “Measuring the Natural Rate of Interest.” Review of Economics and Statistics 85 (4): 1063–70. 

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge.

Explain the difference between the World Wide Web and the Internet.

What is the Internet? The Internet began in 1969 as a project of the U.S. Department of Defense called ARPANET, or Advanced Research Projects Agency Network. The goal of this project was to design a nationwide computer network that could withstand major disasters. If one part of the network was destroyed, the other parts would continue to function due to the decentralized structure of the network. In the early days of ARPANET, there were four computers in the United States attached to the network. Today, there are millions all over the world. Most people define the Internet as a collection of computer networks, but what exactly is a network? A network is a group of two or more computers connected together with cables that allow the computers to share information. Computers that are “on the Internet” all use the same protocols to send information back and forth, allowing them to communicate with each other. As long as a computer uses these protocols, it doesn't matter what type of hardware or software it uses. In the Internet's early days (the 1960s and 1970s), only government, military, and educational institutions had computers connected to the Internet. The Internet was originally designed for research and scholarly communication. But as it grew, its services became more popular, and new ways of using the Internet multiplied. For example, the Internet began to be used for informal communication, entertainment, and eventually commerce, as more businesses connected to the Internet in the 1990s. According to statistics compiled by Nua Internet Surveys Ltd., some 605.60 million people worldwide were connected to the Internet as of September 2002. Today, the Internet remains decentralized, but it is no longer structured entirely around government computers. It is comprised of independently owned and managed individual networks of all sizes. The larger networks with high-speed connections are sometimes called backbone providers. Internet Service Providers (ISPs) lease Internet connections from the backbone providers and sell connections (also called Internet accounts) to consumers. Most home and small business users connect to the Internet with dial-up accounts to ISPs using a modem and special communications software. Uses for the Internet The Internet has a special significance for the library community because it allows patrons -- both children and adults -- who do not have computers to keep up with the Internet for business and academic purposes. Libraries, to a great extent, help bridge what is called the "digital divide." The services listed below would be unattainable for many unless they were provided free of charge by the community's public library. · E-mail allows libraries and patrons to send messages back and forth to individuals or groups. · Telnet allows libraries and patrons to connect to a remote computer and use it as if you were there. · File Transfer Protocol (FTP) allows libraries to transfer files to and from other computers. · Usenet allows libraries and patrons to participate in group discussions on specific topics. · Internet Relay Chat (IRC) allows libraries and patrons to chat in real time with one or many users. · World Wide Web allows libraries and patrons access to literally millions of Web sites worldwide. What is the World Wide Web? One reason for the Internet's growth explosion is the ease of use and popularity of the World Wide Web and its graphical, “point-and-click” user interface. The World Wide Web was invented in 1989 by Tim Berners-Lee, a scientist at the European Particle Physics Laboratory (CERN) in Geneva, Switzerland. Lee wanted to make the information he used for research on the Internet more organized and accessible. The World Wide Web is based on hypertext, which is a method of linking documents using embedded hyperlinks. Hyperlinks can be text, which is usually underlined or a different color than the main text, or graphics. World Wide Web documents are created using a special computer language called HTML (Hypertext Markup Language). HTML coding embeds clickable links in documents and enables simple formatting. Documents written in HTML are stored in computers called servers. Any Internet user who has a Web browser can retrieve the documents. A Web browser is a computer program that knows how to read and display hypertext documents. It also knows how to communicate with servers that store HTML files. The protocol used for this kind of communication is called Hypertext Transfer Protocol (HTTP). Documents on the World Wide Web are called Web pages. Web pages are organized into Web sites. Each Web page has its own address, known formally as a Uniform Resource Locator or URL. Here is a made-up example of a URL for a page on the CNN site: http://www.cnn.com/WEATHER/cities/asiapcf.html. · http:// is the protocol used to retrieve the document. · www.cnn.com is the domain name for the server where the document is stored. · /WEATHER/cities/ is the path to the document in the server's directory structure. · asiapcf.html is the name of the actual HTML file. When you enter a URL in a Web browser, or if you click a hypertext link, the browser sends a message using the HTTP protocol to the computer identified in the URL. This message contains a request for the document specified in the URL. The server sends a copy of the document back to the browser, and it is displayed on your screen. Understanding a few things about URLs and other Internet addresses can make using the Web a lot easier. The domain name (the name of the computer) in a URL can be assigned by a large number of businesses. Just type "domain name" into your search engine, and you will find companies who can register your top level domain name. The Internet Corporation for Assigned Names and Numbers (ICANN) Web site at www.icann.org has a long list of accredited domain name registrars. There are standard suffixes for domain names, called extensions, which help identify what type of organization owns the domain. For example, domain names ending in .com indicate a commercial organization. Common extensions to domain names include: · .net is used for major networks (such as a backbone provider), but is also in general use · .edu is used for colleges and universities. · .gov is used for U.S. federal government agencies. · .mil is used for U.S. military organizations. · .org is commonly used for nonprofit and other organizations. Because so many domain names were snapped up at a rapid pace, more top level domains have been created. In the latter part of 2000, ICANN selected seven new top-level domains (TLDs): · .aero is used to the air transport industry. · .biz is used for all-purpose business sites. · .coop is used for cooperatives. · .info has unrestricted use. · .museum is used for museums. · .name is used for individual Web sites. · .pro is used for professionals such as doctors, lawyers, accountants, and others. Domain names in countries outside the United States usually end with a two-letter code representing the country; for example, Canadian Web sites end in .ca. Some state and county Web pages, including many belonging to libraries, have domain names ending in .us.

This task requires you to answer questions based solely on the information provided in the prompt. You are not allowed to use any external resources or prior knowledge. What is the Internet? The Internet began in 1969 as a project of the U.S. Department of Defense called ARPANET, or Advanced Research Projects Agency Network. The goal of this project was to design a nationwide computer network that could withstand major disasters. If one part of the network was destroyed, the other parts would continue to function due to the decentralized structure of the network. In the early days of ARPANET, there were four computers in the United States attached to the network. Today, there are millions all over the world. Most people define the Internet as a collection of computer networks, but what exactly is a network? A network is a group of two or more computers connected together with cables that allow the computers to share information. Computers that are “on the Internet” all use the same protocols to send information back and forth, allowing them to communicate with each other. As long as a computer uses these protocols, it doesn't matter what type of hardware or software it uses. In the Internet's early days (the 1960s and 1970s), only government, military, and educational institutions had computers connected to the Internet. The Internet was originally designed for research and scholarly communication. But as it grew, its services became more popular, and new ways of using the Internet multiplied. For example, the Internet began to be used for informal communication, entertainment, and eventually commerce, as more businesses connected to the Internet in the 1990s. According to statistics compiled by Nua Internet Surveys Ltd., some 605.60 million people worldwide were connected to the Internet as of September 2002. Today, the Internet remains decentralized, but it is no longer structured entirely around government computers. It is comprised of independently owned and managed individual networks of all sizes. The larger networks with high-speed connections are sometimes called backbone providers. Internet Service Providers (ISPs) lease Internet connections from the backbone providers and sell connections (also called Internet accounts) to consumers. Most home and small business users connect to the Internet with dial-up accounts to ISPs using a modem and special communications software. Uses for the Internet The Internet has a special significance for the library community because it allows patrons -- both children and adults -- who do not have computers to keep up with the Internet for business and academic purposes. Libraries, to a great extent, help bridge what is called the "digital divide." The services listed below would be unattainable for many unless they were provided free of charge by the community's public library. · E-mail allows libraries and patrons to send messages back and forth to individuals or groups. · Telnet allows libraries and patrons to connect to a remote computer and use it as if you were there. · File Transfer Protocol (FTP) allows libraries to transfer files to and from other computers. · Usenet allows libraries and patrons to participate in group discussions on specific topics. · Internet Relay Chat (IRC) allows libraries and patrons to chat in real time with one or many users. · World Wide Web allows libraries and patrons access to literally millions of Web sites worldwide. What is the World Wide Web? One reason for the Internet's growth explosion is the ease of use and popularity of the World Wide Web and its graphical, “point-and-click” user interface. The World Wide Web was invented in 1989 by Tim Berners-Lee, a scientist at the European Particle Physics Laboratory (CERN) in Geneva, Switzerland. Lee wanted to make the information he used for research on the Internet more organized and accessible. The World Wide Web is based on hypertext, which is a method of linking documents using embedded hyperlinks. Hyperlinks can be text, which is usually underlined or a different color than the main text, or graphics. World Wide Web documents are created using a special computer language called HTML (Hypertext Markup Language). HTML coding embeds clickable links in documents and enables simple formatting. Documents written in HTML are stored in computers called servers. Any Internet user who has a Web browser can retrieve the documents. A Web browser is a computer program that knows how to read and display hypertext documents. It also knows how to communicate with servers that store HTML files. The protocol used for this kind of communication is called Hypertext Transfer Protocol (HTTP). Documents on the World Wide Web are called Web pages. Web pages are organized into Web sites. Each Web page has its own address, known formally as a Uniform Resource Locator or URL. Here is a made-up example of a URL for a page on the CNN site: http://www.cnn.com/WEATHER/cities/asiapcf.html. · http:// is the protocol used to retrieve the document. · www.cnn.com is the domain name for the server where the document is stored. · /WEATHER/cities/ is the path to the document in the server's directory structure. · asiapcf.html is the name of the actual HTML file. When you enter a URL in a Web browser, or if you click a hypertext link, the browser sends a message using the HTTP protocol to the computer identified in the URL. This message contains a request for the document specified in the URL. The server sends a copy of the document back to the browser, and it is displayed on your screen. Understanding a few things about URLs and other Internet addresses can make using the Web a lot easier. The domain name (the name of the computer) in a URL can be assigned by a large number of businesses. Just type "domain name" into your search engine, and you will find companies who can register your top level domain name. The Internet Corporation for Assigned Names and Numbers (ICANN) Web site at www.icann.org has a long list of accredited domain name registrars. There are standard suffixes for domain names, called extensions, which help identify what type of organization owns the domain. For example, domain names ending in .com indicate a commercial organization. Common extensions to domain names include: · .net is used for major networks (such as a backbone provider), but is also in general use · .edu is used for colleges and universities. · .gov is used for U.S. federal government agencies. · .mil is used for U.S. military organizations. · .org is commonly used for nonprofit and other organizations. Because so many domain names were snapped up at a rapid pace, more top level domains have been created. In the latter part of 2000, ICANN selected seven new top-level domains (TLDs): · .aero is used to the air transport industry. · .biz is used for all-purpose business sites. · .coop is used for cooperatives. · .info has unrestricted use. · .museum is used for museums. · .name is used for individual Web sites. · .pro is used for professionals such as doctors, lawyers, accountants, and others. Domain names in countries outside the United States usually end with a two-letter code representing the country; for example, Canadian Web sites end in .ca. Some state and county Web pages, including many belonging to libraries, have domain names ending in .us. Explain the difference between the World Wide Web and the Internet.

Using the provided information only, list the answers in bullet points with concise explanations.

When is prompt outside help needed?

Please note that Oura Services are not intended to diagnose, treat, cure, or prevent any disease or medical condition. The information and guidance in Oura Services are there for informational purposes only and cannot replace the services of health professionals or physicians. You should always consult a physician if you have any questions regarding a medical condition or any changes you intend to make to your sleep or activity based on information or guidance from Oura Services. Never disregard or delay in seeking professional medical advice because of something you’ve read from Oura Services. We are not responsible for any health problems that may result from information or guidance you receive from Oura Services. If you make any change to your sleep or activity based on Oura Services, you agree that you do so fully at your own risk. It is important to be sensitive to your body’s responses. For example, if you feel unexpected, repeated or long term pain, fatigue or discomfort due to having made changes to your sleep or activity, it is recommended that you consult a physician before continuing with such changes. The information and guidance in Oura Services may be misleading if your physiological functions and responses differ significantly from population averages due to medical conditions or rare natural differences. Please be cautious that the ring or any other Oura product you wear does not get caught on fixed structures or heavy objects when moving yourself or said heavier objects. If you experience redness or skin irritation on your finger due to the ring or any other Oura product, remove it immediately. If symptoms persist longer than 2-3 days of not using your Oura product, please contact a dermatologist. Finger size can vary depending on the time of the day, and sometimes it may be difficult to remove the ring from your finger. In case the ring gets stuck: → Use cold water and gentle soap to wet your finger, and slowly twist the ring to remove it. → Hold your hand up above your heart until the blood pressure gets lower, and then try to remove it. → In cases of emergency and/or discomfort, when you can’t remove the ring yourself, seek immediate medical attention. Use a soft cloth or hand wash with mild soap and water to clean the ring. Your Oura Ring can be worn during showers, baths, swimming, and snorkeling. Try to avoid wearing the ring when strength training, working with a shovel or other heavy tools, or carrying heavy objects made of metal, ceramics or stone. In addition, try to avoid wearing the ring next to other rings or objects which are made of metal, ceramics, stones or diamonds. The Oura Ring may get scratched and can itself scratch softer metal jewelry or other objects in close contact with the ring like phone covers made of gold, silver, or aluminum. Some ceramic phone covers with a soft coating may also get scratched. Keep the ring away from children. This product is not intended for individuals under the age of 18. Seek immediate medical attention if you know or suspect that a child has swallowed the ring. Do not leave the ring exposed to heat, such as in a vehicle or in the sun. Do not puncture the ring or its battery. Please avoid handling batteries, or working on devices and with machinery that contain batteries while wearing your Oura Ring. In certain cases, where both the cathode and the anode of another battery touch the ring, there is a risk of a short circuit which is similar to standard metallic rings. This can result in a potentially dangerous shock. Please take the proper precautions to avoid these situations.

Using the provided information only, list the answers in bullet points with concise explanations. When is prompt outside help needed? [Please note that Oura Services are not intended to diagnose, treat, cure, or prevent any disease or medical condition. The information and guidance in Oura Services are there for informational purposes only and cannot replace the services of health professionals or physicians. You should always consult a physician if you have any questions regarding a medical condition or any changes you intend to make to your sleep or activity based on information or guidance from Oura Services. Never disregard or delay in seeking professional medical advice because of something you’ve read from Oura Services. We are not responsible for any health problems that may result from information or guidance you receive from Oura Services. If you make any change to your sleep or activity based on Oura Services, you agree that you do so fully at your own risk. It is important to be sensitive to your body’s responses. For example, if you feel unexpected, repeated or long term pain, fatigue or discomfort due to having made changes to your sleep or activity, it is recommended that you consult a physician before continuing with such changes. The information and guidance in Oura Services may be misleading if your physiological functions and responses differ significantly from population averages due to medical conditions or rare natural differences. Please be cautious that the ring or any other Oura product you wear does not get caught on fixed structures or heavy objects when moving yourself or said heavier objects. If you experience redness or skin irritation on your finger due to the ring or any other Oura product, remove it immediately. If symptoms persist longer than 2-3 days of not using your Oura product, please contact a dermatologist. Finger size can vary depending on the time of the day, and sometimes it may be difficult to remove the ring from your finger. In case the ring gets stuck: → Use cold water and gentle soap to wet your finger, and slowly twist the ring to remove it. → Hold your hand up above your heart until the blood pressure gets lower, and then try to remove it. → In cases of emergency and/or discomfort, when you can’t remove the ring yourself, seek immediate medical attention. Use a soft cloth or hand wash with mild soap and water to clean the ring. Your Oura Ring can be worn during showers, baths, swimming, and snorkeling. Try to avoid wearing the ring when strength training, working with a shovel or other heavy tools, or carrying heavy objects made of metal, ceramics or stone. In addition, try to avoid wearing the ring next to other rings or objects which are made of metal, ceramics, stones or diamonds. The Oura Ring may get scratched and can itself scratch softer metal jewelry or other objects in close contact with the ring like phone covers made of gold, silver, or aluminum. Some ceramic phone covers with a soft coating may also get scratched. Keep the ring away from children. This product is not intended for individuals under the age of 18. Seek immediate medical attention if you know or suspect that a child has swallowed the ring. Do not leave the ring exposed to heat, such as in a vehicle or in the sun. Do not puncture the ring or its battery. Please avoid handling batteries, or working on devices and with machinery that contain batteries while wearing your Oura Ring. In certain cases, where both the cathode and the anode of another battery touch the ring, there is a risk of a short circuit which is similar to standard metallic rings. This can result in a potentially dangerous shock. Please take the proper precautions to avoid these situations.]

You must generate a response using only this provided document. Do not use any other outside source to support your claims. If you are unable to answer the request using the supporting document only, then you must respond with "please support more relevant documents so that I may answer your request accurately".

What is neurotechnology?

3/9/24, 4:11 PM Neurotechnology | Technology Networks Neurotechnology Imagine you could control your computer's mouse with your brain instead of your hand1. Imagine helping a patient with spinal cord injury to walk again2 by using a brain implant. It might sound like science fiction, but researchers have figured out how to make both scenarios a reality. It's all thanks to neurotechnology. There are many different types of neurotechnology, each with their role to play. From improving therapeutics for neurological and psychiatric disorders to augmenting current human capability (ever wanted to read someone's mind?) neurotechnology has a wide range of applications that make it a blossoming field worth paying attention to. What is neurotechnology? In its simplest form, neurotechnology is the integration of technical components3 with the nervous system. These components can be computers, electrodes or any other piece of engineering that can be set up to interface with the electric pulses coursing through our bodies. Neurotechnology has two main objectives - either to record signals from the brain and “translate” them into technical control commands (like our braincontrolled computer mouse), or to manipulate brain activity by applying electrical or optical stimuli (to help our paralysis patient). https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 1/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks The applications of neurotechnology are wide-ranging - from furthering the potential of academic research, to therapeutics, to developing brain/machine interfaces and more - and there are a lot of different types of neurotechnologies, some less invasive than others, which we will cover in this article. Electrophysiology In the 1780s, while experimenting with frogs’ legs, Luigi Galvani noticed that applying electric shocks made the legs twitch4 - even though they were disconnected from the frog's brain and body. That breakthrough instigated two centuries of research which would teach us a substantial amount5 about how neurons fire in response to stimuli, and how that firing is carried across different areas of the brain. It was the key that unlocked our understanding of how the brain is organized. In a nutshell6, electrophysiology involves the use of electrodes to understand the electrical properties of neurons. Researchers can record the activity of hundreds of cells at once, or home in on single cells using the patch-clamp technique. An electroencephalogram (EEG) is a type of electrophysiological monitoring method used to record electrical activity of several neurons at once.1 It is typically noninvasive, with the electrodes arranged in a cap and placed over the scalp, which measures voltage fluctuations of the brain regions beneath7. By contrast, an electrocorticogram (ECoG) involves placing electrodes in direct contact with the surface of the brain and measuring the brain waves in those specific brain regions. It is typically used intraoperatively to map epileptic regions of the brain and facilitate their safe removal8. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 2/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Figure 1: Patch-clamp electrophysiology. Credit: Technology Networks In patch-clamp electrophysiology9, a glass micropipette with diameter < 3 microns10 is inserted into the membrane of a single cell. Electrically charged ions passing from the inside to the outside of the cell through the transmembrane channels charge the pipette solution. The electric current generated by this transmembrane movement of ions is detected by a metal electrode, which relays the data to an amplifier. This technique gives researchers incredible precision and certainty in their readings. Researchers can also measure the activity of several neurons at once. There are two main ways of doing this11. Firstly, a microelectrode array can be used. This is a grid of dozens of electrodes which can record the activity of multiple neurons on the surface of the brain. Despite being small in size, it is still too large to be inserted deep in the brain, so this technique is reserved for neurons on the surface of the brain. The second technique involves tetrodes. Tetrodes are microelectrode arrays composed of just four active electrodes - making them small enough to insert https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 3/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks into these deeper regions. Measuring large swathes of neurons like this leads to more uncertainty.5 Some types of neurons have a distinctive waveform, making them easily identifiable. However, these are the exception rather than the rule. Most neurons have ambiguous waveforms, making it difficult to ascertain exactly which neurons have been studied. Deep brain stimulation Deep brain stimulation refers to a technique12 that involves surgically implanting an electrode into specific areas of the brain to modulate the way it operates. These electrodes produce electrical impulses that regulate abnormal neuronal activity in the patient. The stimulation delivered to the brain is regulated by a pacemaker-like device that is implanted under the skin in the upper chest. A wire runs under the skin from this pacemaker to the electrodes. Though highly invasive, this procedure is reversible13 and generally doesn't lead to many side effects. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 4/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Figure 2: A deep brain stimulator includes a pacemaker connected to electrodes in the brain. Credit: Technology Networks. While the exact mechanism of action isn't clear, the therapeutic effects14 of deep brain stimulation can be significant. For example, implanting electrodes into the ventral intermediate nucleus of the thalamus has been shown15 to dramatically decrease tremor, and even halt disease progression in essential tremor patients for more than 6 years after implantation. Additionally, stimulation of either the internal segment of the globus pallidus or the subthalamic nucleus has been shown14 to decrease the symptoms of bradykinesia, rigidity and gait impairment in patients with Parkinson's Disease. Other conditions that benefit from treatment with deep brain stimulation include epilepsy, OCD and dystonia. Transcranial magnetic stimulation https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 5/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Transcranial magnetic stimulation (TMS)16 is a recently developed technique used in the treatment of psychiatric and neurological disorders. It belongs to a growing field of non-invasive brain stimulation (NIBS)17 techniques. TMS exposes the scalp to a magnetic field, which can modulate the electrical signals fired from neurons in the target region. Usually the magnetic field emanates from a "wand-like" device. Though the exact biological mechanism of TMS is not understood, it has been shown to provide relief18 from depressive symptoms and improve mood in some patients. Transcranial direct current stimulation Transcranial direct current stimulation (tDCS) is a method of brain stimulation19 that centers on modulating behavioral and cognitive processes, as well as the neural circuits underlying motor function. Like TMS, tDCS is a painless and non-invasive procedure. Two electrodes are placed on the scalp of the participant - a smaller target electrode on one hemisphere, and a larger reference electrode on the other hemisphere. A weak electrical current passes from the target electrode, through the brain, to the reference electrode - and in doing so, modulates the behavior of the patient. One line of study currently in the spotlight is ADHD therapy. Cognitive control tasks rely on good prefrontal cortex function - the impairment of this region can lead to impulse control issues. Studies have found that adolescents with ADHD exhibit reduced activity in certain prefrontal cortex regions, specifically the left dorsolateral prefrontal cortex (DLPFC). Using tDCS to stimulate the left https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 6/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks DLPFC has been shown to reduce impulsivity in patients with ADHD, by effectively making up for the deficit in activity20. Figure 3: tDCS may be delivered through cap-mounted electrodes. Credit: iStock It is generally accepted21 that a positive anodal, or excitatory, current is associated with upregulation of behaviors regulated by the brain region under the target electrode. On the other hand, negative cathodal, or inhibitory, current is associated with downregulation of said behaviors. tDCS is used to identify22 brain-behavior relationships across cognitive, motor, social and affective domains. Applications of tDCS on healthy populations have been demonstrated23 to temporarily modify behavior, accelerate learning, and boost task performance. Focused ultrasound https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 7/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Breakthrough research24 at Carnegie Mellon University has recently shown that low-intensity ultrasound techniques can be applied to manipulate neurons in a cell-type selective manner. In other words, focused ultrasound (FUS) gives researchers the power to modulate specific neuro-circuits, making FUS a more highly targeted neurotherapy25 than deep brain stimulation, TMS, and tDCS. Figure 4: A diagram showing the mechanisms behind focused ultrasound (FUS). Credit: Technology Networks. FUS neuromodulation works by directing ultrasonic wave energy, through the skull, at highly-targeted brain regions. By tuning the parameters, scientists can either excite or inhibit specific neural circuits. FUS is FDA-approved in the US for treatment of essential tremor26. However, it is still not widely used in hospitals - it is a relatively novel therapy, barely a decade old. It carries several advantages over older therapies for essential tremor, namely being non-invasive, not relying on radiation, and not posing https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 8/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks any risk of infection27. For these reasons, we may see its presence pick up in the coming years. Brain-computer interfaces Simply put, a brain-computer interface (BCI)28 is a computer-based system that receives brain signals, analyzes them and then translates them into commands for devices, which produce a desired output. The main function of BCI in a medical context is therapeutic - restoring normal neuromuscular function to patients with disorders such as amyotrophic lateral sclerosis (ALS), cerebral palsy, stroke or spinal cord injury. Turning brain signals into commands for a computer system means patients will be able to move a cursor, type on a keyboard, manipulate a prosthetic just by using their brain. In 2015, researchers at the University of Houston succeeded in making an amputee control his prosthetic hand using only his mind for the first time - without the need for an invasive brain implant. Instead, the subject wore an 64-channel EEG headset, which monitored brain activity across motor, decision-making and action observation regions of the brain. The neuronal activity in these regions preceded the movement of the prosthetic hand by 50 - 90 milliseconds, proving that the brain was anticipating the movement before it happened29. Beyond this, BCIs also have a role to play in making surgery safer30. For example, BCIs can be used to monitor the surgeon's mental focus while they are performing a procedure, and then use this information to make the procedure safer. This system can train the surgeon to regulate their own mental state while performing surgery-like tasks using a robotic system. The https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 9/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks system presents augmented reality feedback to the surgeon, which helps their effort in maintaining a high level of mental focus during the task. Brain Implants The below video shows a monkey playing Pong with its mind31. As well as being, let’s be honest, pretty strange to watch, it is a beautiful illustration of a brain-computer interface in action. This technology, developed by Elon Musk's company Neuralink, is part of a revival of interest in brain implants. Monkey MindPong Though they might sound like something belonging to the future, the human fascination with brain implants has been around since the early 20th century, with the development of electroencephalography (EEG) by Hans Berger in 1929.32 Brain implants are one of the ways brains and computers interface in the first place. They allow users to communicate to computers and other external devices such as robotic hands. This makes them strong candidates as a therapy for patients who may have nerve damage in their limbs or spinal cord, as the brain implant allows these nerves to be bypassed entirely while still achieving the desired output. The implants record action potentials and local field potentials of neurons with high temporal and spatial resolution and high channel count33. This lets researchers cover lots of neural tissue at once. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 10/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks The implantation is currently delivered manually, by a surgeon, via a craniotomy. While it is certainly invasive, the procedure is reversible34 without any serious side-effects, at least in the pigs that Musk has also experimented on. While Musk's vision for Neuralink is to offer its brain technology as an elective procedure35 for any average person, other brain implant companies are thinking differently. For example, Florian Solzbacher is clear that the development of nonimplantable BCIs32 are also of great interest to his company Blackrock Neurotech. According to the company, just 34 people in the world currently have a device implanted in their brains - this neurotechnology is clearly still in its infancy. That said, Blackrock's MoveAgain BCI implant recently gained Breakthrough Device designation from the FDA, and the company intends to commercialize MoveAgain this year36. It wouldn't be a stretch to imagine we may be standing on the precipice of brain implants taking off as a standard therapy for several debilitating, chronic conditions. Ethics of neurotechnology If reading about all these developments in neurotechnology has made you uncomfortable, you're not alone. Continue reading below... https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 11/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Neurotechnology, while therapeutically very promising, is an ethical minefield. It raises questions around rights to data, privacy, and the risk of side-stepping regulations in the name of easier marketing. Let's think back to our Pong-playing monkey. The researchers monitoring Pager's neuroactivity have that data on their computers. Who owns that data? Is it Pager's, or Neuralink's? Moving a cursor on a screen is one thing, but what if the neural activity encoded is more sensitive than that? What kind of rules around privacy exist to protect the user? These are all questions that need to be considered. The rapid rise in interest in neurotechnology has also meant regulation has been slow to keep up. Because the way products are marketed informs the regulations they need to comply with, there is a fear that companies are sidestepping critical checks37 by marketing their neurotechnologies as "wellness" products rather than medical devices. Conclusion The field of neurotechnology encompasses many techniques and types of technology. From being able to record the activity of a single neuron firing, to https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 12/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks modulating the activity of entire brain regions, there's no doubt neurotechnology is and will continue to change the way we treat neurological and psychiatric conditions. As Florien Solzbacher of Blackrock Neurotech put it, "I do foresee that in 20-30 years, these types of implants will be just as common and acceptable as cardiac pacemakers are today."33 If Solzbacher's predictions come true, it will change the game for sufferers of dementia, mood disorders and neurodegenerative diseases. Neurotechnology has the potential to help us diminish the symptoms of these diseases, but also to augment the human experience. We just have to be open to it. About the author: Julia is a location-independent writer with a passion for communicating scientific ideas to the public. She holds a BSc (Hons) in Medical Science and a MSc in Sustainable Agriculture, and loves writing about neuroscience, behaviour, agriculture, ecology, conservation, and more. In her free time she loves dancing, hiking, and making music. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 13/13 

You must generate a response using only this provided document. Do not use any other outside source to support your claims. If you are unable to answer the request using the supporting document only, then you must respond with "please support more relevant documents so that I may answer your request accurately". What is neurotechnology? 3/9/24, 4:11 PM Neurotechnology | Technology Networks Neurotechnology Imagine you could control your computer's mouse with your brain instead of your hand1. Imagine helping a patient with spinal cord injury to walk again2 by using a brain implant. It might sound like science fiction, but researchers have figured out how to make both scenarios a reality. It's all thanks to neurotechnology. There are many different types of neurotechnology, each with their role to play. From improving therapeutics for neurological and psychiatric disorders to augmenting current human capability (ever wanted to read someone's mind?) neurotechnology has a wide range of applications that make it a blossoming field worth paying attention to. What is neurotechnology? In its simplest form, neurotechnology is the integration of technical components3 with the nervous system. These components can be computers, electrodes or any other piece of engineering that can be set up to interface with the electric pulses coursing through our bodies. Neurotechnology has two main objectives - either to record signals from the brain and “translate” them into technical control commands (like our braincontrolled computer mouse), or to manipulate brain activity by applying electrical or optical stimuli (to help our paralysis patient). https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 1/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks The applications of neurotechnology are wide-ranging - from furthering the potential of academic research, to therapeutics, to developing brain/machine interfaces and more - and there are a lot of different types of neurotechnologies, some less invasive than others, which we will cover in this article. Electrophysiology In the 1780s, while experimenting with frogs’ legs, Luigi Galvani noticed that applying electric shocks made the legs twitch4 - even though they were disconnected from the frog's brain and body. That breakthrough instigated two centuries of research which would teach us a substantial amount5 about how neurons fire in response to stimuli, and how that firing is carried across different areas of the brain. It was the key that unlocked our understanding of how the brain is organized. In a nutshell6, electrophysiology involves the use of electrodes to understand the electrical properties of neurons. Researchers can record the activity of hundreds of cells at once, or home in on single cells using the patch-clamp technique. An electroencephalogram (EEG) is a type of electrophysiological monitoring method used to record electrical activity of several neurons at once.1 It is typically noninvasive, with the electrodes arranged in a cap and placed over the scalp, which measures voltage fluctuations of the brain regions beneath7. By contrast, an electrocorticogram (ECoG) involves placing electrodes in direct contact with the surface of the brain and measuring the brain waves in those specific brain regions. It is typically used intraoperatively to map epileptic regions of the brain and facilitate their safe removal8. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 2/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Figure 1: Patch-clamp electrophysiology. Credit: Technology Networks In patch-clamp electrophysiology9, a glass micropipette with diameter < 3 microns10 is inserted into the membrane of a single cell. Electrically charged ions passing from the inside to the outside of the cell through the transmembrane channels charge the pipette solution. The electric current generated by this transmembrane movement of ions is detected by a metal electrode, which relays the data to an amplifier. This technique gives researchers incredible precision and certainty in their readings. Researchers can also measure the activity of several neurons at once. There are two main ways of doing this11. Firstly, a microelectrode array can be used. This is a grid of dozens of electrodes which can record the activity of multiple neurons on the surface of the brain. Despite being small in size, it is still too large to be inserted deep in the brain, so this technique is reserved for neurons on the surface of the brain. The second technique involves tetrodes. Tetrodes are microelectrode arrays composed of just four active electrodes - making them small enough to insert https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 3/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks into these deeper regions. Measuring large swathes of neurons like this leads to more uncertainty.5 Some types of neurons have a distinctive waveform, making them easily identifiable. However, these are the exception rather than the rule. Most neurons have ambiguous waveforms, making it difficult to ascertain exactly which neurons have been studied. Deep brain stimulation Deep brain stimulation refers to a technique12 that involves surgically implanting an electrode into specific areas of the brain to modulate the way it operates. These electrodes produce electrical impulses that regulate abnormal neuronal activity in the patient. The stimulation delivered to the brain is regulated by a pacemaker-like device that is implanted under the skin in the upper chest. A wire runs under the skin from this pacemaker to the electrodes. Though highly invasive, this procedure is reversible13 and generally doesn't lead to many side effects. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 4/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Figure 2: A deep brain stimulator includes a pacemaker connected to electrodes in the brain. Credit: Technology Networks. While the exact mechanism of action isn't clear, the therapeutic effects14 of deep brain stimulation can be significant. For example, implanting electrodes into the ventral intermediate nucleus of the thalamus has been shown15 to dramatically decrease tremor, and even halt disease progression in essential tremor patients for more than 6 years after implantation. Additionally, stimulation of either the internal segment of the globus pallidus or the subthalamic nucleus has been shown14 to decrease the symptoms of bradykinesia, rigidity and gait impairment in patients with Parkinson's Disease. Other conditions that benefit from treatment with deep brain stimulation include epilepsy, OCD and dystonia. Transcranial magnetic stimulation https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 5/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Transcranial magnetic stimulation (TMS)16 is a recently developed technique used in the treatment of psychiatric and neurological disorders. It belongs to a growing field of non-invasive brain stimulation (NIBS)17 techniques. TMS exposes the scalp to a magnetic field, which can modulate the electrical signals fired from neurons in the target region. Usually the magnetic field emanates from a "wand-like" device. Though the exact biological mechanism of TMS is not understood, it has been shown to provide relief18 from depressive symptoms and improve mood in some patients. Transcranial direct current stimulation Transcranial direct current stimulation (tDCS) is a method of brain stimulation19 that centers on modulating behavioral and cognitive processes, as well as the neural circuits underlying motor function. Like TMS, tDCS is a painless and non-invasive procedure. Two electrodes are placed on the scalp of the participant - a smaller target electrode on one hemisphere, and a larger reference electrode on the other hemisphere. A weak electrical current passes from the target electrode, through the brain, to the reference electrode - and in doing so, modulates the behavior of the patient. One line of study currently in the spotlight is ADHD therapy. Cognitive control tasks rely on good prefrontal cortex function - the impairment of this region can lead to impulse control issues. Studies have found that adolescents with ADHD exhibit reduced activity in certain prefrontal cortex regions, specifically the left dorsolateral prefrontal cortex (DLPFC). Using tDCS to stimulate the left https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 6/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks DLPFC has been shown to reduce impulsivity in patients with ADHD, by effectively making up for the deficit in activity20. Figure 3: tDCS may be delivered through cap-mounted electrodes. Credit: iStock It is generally accepted21 that a positive anodal, or excitatory, current is associated with upregulation of behaviors regulated by the brain region under the target electrode. On the other hand, negative cathodal, or inhibitory, current is associated with downregulation of said behaviors. tDCS is used to identify22 brain-behavior relationships across cognitive, motor, social and affective domains. Applications of tDCS on healthy populations have been demonstrated23 to temporarily modify behavior, accelerate learning, and boost task performance. Focused ultrasound https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 7/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Breakthrough research24 at Carnegie Mellon University has recently shown that low-intensity ultrasound techniques can be applied to manipulate neurons in a cell-type selective manner. In other words, focused ultrasound (FUS) gives researchers the power to modulate specific neuro-circuits, making FUS a more highly targeted neurotherapy25 than deep brain stimulation, TMS, and tDCS. Figure 4: A diagram showing the mechanisms behind focused ultrasound (FUS). Credit: Technology Networks. FUS neuromodulation works by directing ultrasonic wave energy, through the skull, at highly-targeted brain regions. By tuning the parameters, scientists can either excite or inhibit specific neural circuits. FUS is FDA-approved in the US for treatment of essential tremor26. However, it is still not widely used in hospitals - it is a relatively novel therapy, barely a decade old. It carries several advantages over older therapies for essential tremor, namely being non-invasive, not relying on radiation, and not posing https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 8/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks any risk of infection27. For these reasons, we may see its presence pick up in the coming years. Brain-computer interfaces Simply put, a brain-computer interface (BCI)28 is a computer-based system that receives brain signals, analyzes them and then translates them into commands for devices, which produce a desired output. The main function of BCI in a medical context is therapeutic - restoring normal neuromuscular function to patients with disorders such as amyotrophic lateral sclerosis (ALS), cerebral palsy, stroke or spinal cord injury. Turning brain signals into commands for a computer system means patients will be able to move a cursor, type on a keyboard, manipulate a prosthetic just by using their brain. In 2015, researchers at the University of Houston succeeded in making an amputee control his prosthetic hand using only his mind for the first time - without the need for an invasive brain implant. Instead, the subject wore an 64-channel EEG headset, which monitored brain activity across motor, decision-making and action observation regions of the brain. The neuronal activity in these regions preceded the movement of the prosthetic hand by 50 - 90 milliseconds, proving that the brain was anticipating the movement before it happened29. Beyond this, BCIs also have a role to play in making surgery safer30. For example, BCIs can be used to monitor the surgeon's mental focus while they are performing a procedure, and then use this information to make the procedure safer. This system can train the surgeon to regulate their own mental state while performing surgery-like tasks using a robotic system. The https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 9/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks system presents augmented reality feedback to the surgeon, which helps their effort in maintaining a high level of mental focus during the task. Brain Implants The below video shows a monkey playing Pong with its mind31. As well as being, let’s be honest, pretty strange to watch, it is a beautiful illustration of a brain-computer interface in action. This technology, developed by Elon Musk's company Neuralink, is part of a revival of interest in brain implants. Monkey MindPong Though they might sound like something belonging to the future, the human fascination with brain implants has been around since the early 20th century, with the development of electroencephalography (EEG) by Hans Berger in 1929.32 Brain implants are one of the ways brains and computers interface in the first place. They allow users to communicate to computers and other external devices such as robotic hands. This makes them strong candidates as a therapy for patients who may have nerve damage in their limbs or spinal cord, as the brain implant allows these nerves to be bypassed entirely while still achieving the desired output. The implants record action potentials and local field potentials of neurons with high temporal and spatial resolution and high channel count33. This lets researchers cover lots of neural tissue at once. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 10/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks The implantation is currently delivered manually, by a surgeon, via a craniotomy. While it is certainly invasive, the procedure is reversible34 without any serious side-effects, at least in the pigs that Musk has also experimented on. While Musk's vision for Neuralink is to offer its brain technology as an elective procedure35 for any average person, other brain implant companies are thinking differently. For example, Florian Solzbacher is clear that the development of nonimplantable BCIs32 are also of great interest to his company Blackrock Neurotech. According to the company, just 34 people in the world currently have a device implanted in their brains - this neurotechnology is clearly still in its infancy. That said, Blackrock's MoveAgain BCI implant recently gained Breakthrough Device designation from the FDA, and the company intends to commercialize MoveAgain this year36. It wouldn't be a stretch to imagine we may be standing on the precipice of brain implants taking off as a standard therapy for several debilitating, chronic conditions. Ethics of neurotechnology If reading about all these developments in neurotechnology has made you uncomfortable, you're not alone. Continue reading below... https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 11/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks Neurotechnology, while therapeutically very promising, is an ethical minefield. It raises questions around rights to data, privacy, and the risk of side-stepping regulations in the name of easier marketing. Let's think back to our Pong-playing monkey. The researchers monitoring Pager's neuroactivity have that data on their computers. Who owns that data? Is it Pager's, or Neuralink's? Moving a cursor on a screen is one thing, but what if the neural activity encoded is more sensitive than that? What kind of rules around privacy exist to protect the user? These are all questions that need to be considered. The rapid rise in interest in neurotechnology has also meant regulation has been slow to keep up. Because the way products are marketed informs the regulations they need to comply with, there is a fear that companies are sidestepping critical checks37 by marketing their neurotechnologies as "wellness" products rather than medical devices. Conclusion The field of neurotechnology encompasses many techniques and types of technology. From being able to record the activity of a single neuron firing, to https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 12/13 3/9/24, 4:11 PM Neurotechnology | Technology Networks modulating the activity of entire brain regions, there's no doubt neurotechnology is and will continue to change the way we treat neurological and psychiatric conditions. As Florien Solzbacher of Blackrock Neurotech put it, "I do foresee that in 20-30 years, these types of implants will be just as common and acceptable as cardiac pacemakers are today."33 If Solzbacher's predictions come true, it will change the game for sufferers of dementia, mood disorders and neurodegenerative diseases. Neurotechnology has the potential to help us diminish the symptoms of these diseases, but also to augment the human experience. We just have to be open to it. About the author: Julia is a location-independent writer with a passion for communicating scientific ideas to the public. She holds a BSc (Hons) in Medical Science and a MSc in Sustainable Agriculture, and loves writing about neuroscience, behaviour, agriculture, ecology, conservation, and more. In her free time she loves dancing, hiking, and making music. https://www.technologynetworks.com/neuroscience/articles/neurotechnology-358488 13/13 

Simplify the language used so it's easier to understand. Only pull information from the provided document.

What is the short title of the act?

1ST SESSION, 43RD LEGISLATURE, ONTARIO 2 CHARLES III, 2023 Bill 152 An Act to amend the Highway Traffic Act to prohibit passing on a highway painted with double solid yellow lines Mr. G. Bourgouin Private Member’s Bill 1st Reading November 21, 2023 2nd Reading 3rd Reading Royal Assent Bill 152 2023 An Act to amend the Highway Traffic Act to prohibit passing on a highway painted with double solid yellow lines His Majesty, by and with the advice and consent of the Legislative Assembly of the Province of Ontario, enacts as follows: 1 Section 148 of the Highway Traffic Act is amended by adding the following subsection: Double solid yellow lines (9) No person in charge of a vehicle shall pass or attempt to pass another vehicle going in the same direction on a highway if doing so would require the crossing of double solid yellow lines painted on the roadway. Offence (10) Every person who contravenes subsection (9) is guilty of an offence and on conviction is liable to, (a) a fine of $400; and (b) three or more demerit points under Ontario Regulation 339/94 (Demerit Point System) made under this Act. Commencement 2 This Act comes into force on the day it receives Royal Assent. Short title 3 The short title of this Act is the Chad’s Law (Enforcing Safer Passing), 2023. ______________ EXPLANATORY NOTE Section 148 of the Highway Traffic Act is amended to prohibit passing or attempting to pass another vehicle going in the same direction on a highway if doing so would require the crossing of double solid yellow lines painted on the roadway. Every person who contravenes this prohibition is guilty of an offence and on conviction is liable to a fine of $400 and three or more demerit points.

Simplify the language used so it's easier to understand. Only pull information from the provided document. What is the short title of the act? 1ST SESSION, 43RD LEGISLATURE, ONTARIO 2 CHARLES III, 2023 Bill 152 An Act to amend the Highway Traffic Act to prohibit passing on a highway painted with double solid yellow lines Mr. G. Bourgouin Private Member’s Bill 1st Reading November 21, 2023 2nd Reading 3rd Reading Royal Assent Bill 152 2023 An Act to amend the Highway Traffic Act to prohibit passing on a highway painted with double solid yellow lines His Majesty, by and with the advice and consent of the Legislative Assembly of the Province of Ontario, enacts as follows: 1 Section 148 of the Highway Traffic Act is amended by adding the following subsection: Double solid yellow lines (9) No person in charge of a vehicle shall pass or attempt to pass another vehicle going in the same direction on a highway if doing so would require the crossing of double solid yellow lines painted on the roadway. Offence (10) Every person who contravenes subsection (9) is guilty of an offence and on conviction is liable to, (a) a fine of $400; and (b) three or more demerit points under Ontario Regulation 339/94 (Demerit Point System) made under this Act. Commencement 2 This Act comes into force on the day it receives Royal Assent. Short title 3 The short title of this Act is the Chad’s Law (Enforcing Safer Passing), 2023. ______________ EXPLANATORY NOTE Section 148 of the Highway Traffic Act is amended to prohibit passing or attempting to pass another vehicle going in the same direction on a highway if doing so would require the crossing of double solid yellow lines painted on the roadway. Every person who contravenes this prohibition is guilty of an offence and on conviction is liable to a fine of $400 and three or more demerit points.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Over the past 50 the percentage of Americans suffering from obesity has increased dramatically. Is it our fault we're becoming fatter? What role does the quality of food and crops play? What role do additives, synthetic chemicals, hormones, and GMO crops play? Is the government doing enough to protect us? How do we avoid or lessen our exposure to toxic chemicals?

Chemicals in our food may be contributing to weight gain It’s no secret rates of overweight, obesity and other metabolic diseases are skyrocketing. And food is a big part of the problem, though not in the way you might think. It isn’t just how many calories we consume and burn. The nutritional value of food and how much it’s processed also play a role in how what we eat affects our weight. Another likely culprit behind weight gain is the harmful chemicals in what we consume. Some of these substances, called obesogens, can contribute to weight gain and lead to obesity, in turn raising a person’s risk of heart disease and other serious health problems. Scientists have found evidence of about 50 of these chemicals. They can be found in many consumer products, as well as in polluted air and water. But one of the most important ways we’re exposed is by consuming contaminated food. Harmful ingredients hiding in plain sight Studies show a link between highly processed foods – typically not very nutritious, with high levels of trans fat, sugar and sodium – and higher risk of metabolic diseases that, in turn, can lead to health problems, including heart disease, stroke and cancer, which are significant causes of preventable illness and death. Processed foods, from fast food to some “healthy” products like protein bars and vegetarian microwave meals, often have many artificial ingredients, such as sweeteners, flavor enhancers and preservatives, some of which are obesogens. Some obesogens occur naturally in food. One, fructose, accounts for about 40 percent of sweeteners we consume. But most obesogens in food are artificial chemicals, some added intentionally, particularly in highly processed food. Others contaminate food indirectly, through packaging, residual pesticides, or legacy environmental contamination from industrial chemicals, pesticides and heavy metals. Food additives MSG is a common flavor enhancer that shows obesogenic effects in animals. Artificial sweeteners – particularly aspartame, sucralose and saccharin – is another obesogen found in a wide range of low-calorie and diet food and beverage products. Research suggests some may be obesogenic and others, like most chemicals, haven’t been studied enough for us to know whether they are or not. The preservatives BHA and methyl and butyl paraben are likely obesogenic and can be found in everything from vegetable oils to processed meat and chewing gum to potato chips. Several emulsifiers are potential obesogens. Food contaminants BPA migrates from food packaging into food. PFOA is one of the most notorious types of the “forever chemicals” known as PFAS, used in nonstick cookware, cooking implements and food packaging like takeout containers. PCBs, once used in industrial materials like paint, varnish, plastic, pesticides and coolants, still make their way into some animal products, though they’ve been banned since 1979. Flame retardants – used to treat clothing, bedding, electronics and children’s products, among other items – get into our waterways and eventually our food. Many pesticides have obesogenic properties. Even banned pesticides enter the food supply, because they persist in land used for crops. Regulating or banning obesogens in food Our focus must shift from considering overweight and obesity the result of a personal, moral failing to treating it as a result of environmental exposures and inequitable access to healthy food. This change may already be starting: Some physicians are beginning to approach obesity in their clinical practices from this perspective and looking for ways to limit exposures as an approach to weight loss. But it’s up to the government to protect us from these chemicals: The FDA, Department of Defense and Environmental Protection Agency must ban or restrict the most pervasive and harmful food chemicals. To make sure we face less exposure to these harmful chemicals, lawmakers and regulators must: • Develop greater transparency in food labeling. • Issue stronger recommendations in the Dietary Guidelines, to address other food additives, in addition to natural and artificial sweeteners, sodium and saturated fat. • Provide more funding for programs improving accessibility and availability of healthier food options. • Look for new ways to address environmental injustices that promote racial and ethnic disparities in exposure to obesogens in food. In addition, the White House Conference on Hunger, Nutrition, and Health on September 28 will shine a light on obesogens, among other issues – a chance to meaningfully reduce our exposure to these chemicals. EWG is part of a coalition of organizations that called on President Joe Biden to implement numerous changes to improve Americans’ food, nutrition and health. Two changes would protect us from ongoing exposure to obesogens: • Closing the regulatory loophole that allows chemical companies to introduce new chemicals, some of them obesogens, into the supply chain without approval from the FDA. Many of these substances have never undergone a safety review by the FDA. • Requiring the FDA to identify and reassess food chemicals of concern, including obesogens, already in use. The FDA doesn’t have to routinely reassess the safety of these chemicals. So substances like PFAS, BPA and phthalates remain in use long after evidence emerges linking them to harm to our metabolism and other health risks. What you can do Many obesogens are, at best, tough to avoid. But you can limit your exposure to chemicals added to food intentionally, especially some artificial sweeteners, preservatives and added sugars, like high-fructose corn syrup. To reduce your exposure to harmful chemicals: • Find out about additive names and study the labels of foods you buy to learn what you’re consuming (and can avoid). • Eat lower on the food chain – fresh produce, beans and whole grains don’t contain food additives. • Choose organic fruit and vegetables, when you can, to lower your exposure to pesticides. Consult EWG’s Shopper’s Guide to Pesticides in Produce™ to see which are best to eat organic and which are OK to eat non-organic, if necessary. • Choose organic animal products – or eat less and find other protein sources instead. Antibiotics and hormones accumulate in non-organic animal products. • Avoid plastic and grease- and waterproof food packaging. (And eat less takeout – the packaging may contain PFAS or plastic additives.) • Use glass, ceramic or stainless steel instead of nonstick for cookware, and wood and stainless steel for cooking utensils. • Instead of plastic, use glass, ceramic, or stainless steel containers to store and microwave food. • For water on the go, use stainless steel bottles rather than plastic, which may leach phthalates and BPA. • Avoid plastic labeled with code 7, which indicates the presence of BPA, or 3, which indicates PVC. • Consult EWG’s Tap Water Database to see what’s in your water. Then see which filter is best for your own situation. Avoid bottled water – it may be no better than tap water, and the plastic leaches into the water.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Over the past 50 the percentage of Americans suffering from obesity has increased dramatically. Is it our fault we're becoming fatter? What role does the quality of food and crops play? What role do additives, synthetic chemicals, hormones, and GMO crops play? Is the government doing enough to protect us? How do we avoid or lessen our exposure to toxic chemicals? <TEXT> Chemicals in our food may be contributing to weight gain It’s no secret rates of overweight, obesity and other metabolic diseases are skyrocketing. And food is a big part of the problem, though not in the way you might think. It isn’t just how many calories we consume and burn. The nutritional value of food and how much it’s processed also play a role in how what we eat affects our weight. Another likely culprit behind weight gain is the harmful chemicals in what we consume. Some of these substances, called obesogens, can contribute to weight gain and lead to obesity, in turn raising a person’s risk of heart disease and other serious health problems. Scientists have found evidence of about 50 of these chemicals. They can be found in many consumer products, as well as in polluted air and water. But one of the most important ways we’re exposed is by consuming contaminated food. Harmful ingredients hiding in plain sight Studies show a link between highly processed foods – typically not very nutritious, with high levels of trans fat, sugar and sodium – and higher risk of metabolic diseases that, in turn, can lead to health problems, including heart disease, stroke and cancer, which are significant causes of preventable illness and death. Processed foods, from fast food to some “healthy” products like protein bars and vegetarian microwave meals, often have many artificial ingredients, such as sweeteners, flavor enhancers and preservatives, some of which are obesogens. Some obesogens occur naturally in food. One, fructose, accounts for about 40 percent of sweeteners we consume. But most obesogens in food are artificial chemicals, some added intentionally, particularly in highly processed food. Others contaminate food indirectly, through packaging, residual pesticides, or legacy environmental contamination from industrial chemicals, pesticides and heavy metals. Food additives MSG is a common flavor enhancer that shows obesogenic effects in animals. Artificial sweeteners – particularly aspartame, sucralose and saccharin – is another obesogen found in a wide range of low-calorie and diet food and beverage products. Research suggests some may be obesogenic and others, like most chemicals, haven’t been studied enough for us to know whether they are or not. The preservatives BHA and methyl and butyl paraben are likely obesogenic and can be found in everything from vegetable oils to processed meat and chewing gum to potato chips. Several emulsifiers are potential obesogens. Food contaminants BPA migrates from food packaging into food. PFOA is one of the most notorious types of the “forever chemicals” known as PFAS, used in nonstick cookware, cooking implements and food packaging like takeout containers. PCBs, once used in industrial materials like paint, varnish, plastic, pesticides and coolants, still make their way into some animal products, though they’ve been banned since 1979. Flame retardants – used to treat clothing, bedding, electronics and children’s products, among other items – get into our waterways and eventually our food. Many pesticides have obesogenic properties. Even banned pesticides enter the food supply, because they persist in land used for crops. Regulating or banning obesogens in food Our focus must shift from considering overweight and obesity the result of a personal, moral failing to treating it as a result of environmental exposures and inequitable access to healthy food. This change may already be starting: Some physicians are beginning to approach obesity in their clinical practices from this perspective and looking for ways to limit exposures as an approach to weight loss. But it’s up to the government to protect us from these chemicals: The FDA, Department of Defense and Environmental Protection Agency must ban or restrict the most pervasive and harmful food chemicals. To make sure we face less exposure to these harmful chemicals, lawmakers and regulators must: • Develop greater transparency in food labeling. • Issue stronger recommendations in the Dietary Guidelines, to address other food additives, in addition to natural and artificial sweeteners, sodium and saturated fat. • Provide more funding for programs improving accessibility and availability of healthier food options. • Look for new ways to address environmental injustices that promote racial and ethnic disparities in exposure to obesogens in food. In addition, the White House Conference on Hunger, Nutrition, and Health on September 28 will shine a light on obesogens, among other issues – a chance to meaningfully reduce our exposure to these chemicals. EWG is part of a coalition of organizations that called on President Joe Biden to implement numerous changes to improve Americans’ food, nutrition and health. Two changes would protect us from ongoing exposure to obesogens: • Closing the regulatory loophole that allows chemical companies to introduce new chemicals, some of them obesogens, into the supply chain without approval from the FDA. Many of these substances have never undergone a safety review by the FDA. • Requiring the FDA to identify and reassess food chemicals of concern, including obesogens, already in use. The FDA doesn’t have to routinely reassess the safety of these chemicals. So substances like PFAS, BPA and phthalates remain in use long after evidence emerges linking them to harm to our metabolism and other health risks. What you can do Many obesogens are, at best, tough to avoid. But you can limit your exposure to chemicals added to food intentionally, especially some artificial sweeteners, preservatives and added sugars, like high-fructose corn syrup. To reduce your exposure to harmful chemicals: • Find out about additive names and study the labels of foods you buy to learn what you’re consuming (and can avoid). • Eat lower on the food chain – fresh produce, beans and whole grains don’t contain food additives. • Choose organic fruit and vegetables, when you can, to lower your exposure to pesticides. Consult EWG’s Shopper’s Guide to Pesticides in Produce™ to see which are best to eat organic and which are OK to eat non-organic, if necessary. • Choose organic animal products – or eat less and find other protein sources instead. Antibiotics and hormones accumulate in non-organic animal products. • Avoid plastic and grease- and waterproof food packaging. (And eat less takeout – the packaging may contain PFAS or plastic additives.) • Use glass, ceramic or stainless steel instead of nonstick for cookware, and wood and stainless steel for cooking utensils. • Instead of plastic, use glass, ceramic, or stainless steel containers to store and microwave food. • For water on the go, use stainless steel bottles rather than plastic, which may leach phthalates and BPA. • Avoid plastic labeled with code 7, which indicates the presence of BPA, or 3, which indicates PVC. • Consult EWG’s Tap Water Database to see what’s in your water. Then see which filter is best for your own situation. Avoid bottled water – it may be no better than tap water, and the plastic leaches into the water. https://www.ewg.org/news-insights/news/2022/09/chemicals-our-food-may-be-contributing-weight-gain

Your answer must be drawn from the context block provided, only. You are prohibited from using other sources or drawing from prior knowledge. Provide a brief, bolded heading for your response that gives context. The body of the answer should be no longer than 200 words.

What new requirements for states would the proposed FY2024 legislation create?

Unemployment Insurance: Legislative Issues in the 118th Congress Congressional Research Service 12 President’s Budget Proposal for FY2024 The FY2024 budget request included several provisions intended to improve the administration and integrity of the UI program.51 These provisions included updating the factors used in determining administrative funding levels, a package of integrity-focused provisions, funding to continue to address fraud and IT modernization within the UI system, and additional funding to continue to build and support the UI Integrity Center’s Integrity Data Hub (IDH) cross-match systems. It also included an additional, broader package of proposed reforms to address systemic fraud such as identity theft and other fraud in the UI program, increase funding for the COVID-19 Fraud Strike Force Teams, and provide additional funding for Inspectors General (including the DOL Inspector General). Proposed UI Program Administrative Funding The FY2024 budget request included $3.5 billion for administration of the UI system, which was an increase over the FY2023 budget request amount of $3.1 billion.52 This amount included almost $3.0 billion “reflecting the Administration’s economic assumptions and updated workload- processing and salary factors” to administer UI.53 Additionally, the budget request for UI administration included $550 million in funding for RESEA. Separately, the budget request would have provided a fourth installment of $6 million to modernize IT infrastructure and would also have provided $150 million for program integrity purposes, including state grants to reduce fraud through identity verification services and other IT infrastructure improvements. The President’s budget proposal for FY2024 also proposed an alteration to the formula that determines the federal appropriation for state UI administration, which would have been the first substantive update in decades. Specifically, this proposal would have updated assumptions related to UI claims processing and state UI workforce salary rates, as prior assumptions for these factors were not capturing current administrative costs in states. Proposed Program Integrity Legislation The President’s FY2024 budget request also recommended a package of legislative changes to improve UI program integrity and to provide additional funding to states to help ensure proper UI payments. These proposals would have • codifed the requirement for states to data match with the National Directory of New Hires (NDNH; administered by the Department of Health and Human Services) and the Prisoner Update Processing System (PUPS, administered by the Social Security Administration) to help ensure that UI benefits are correctly paid to eligible individuals in a timely manner;54 51 DOL, Fiscal 2024 Budget, Volume 1: FY2024 Congressional Budget Justification, Employment and Training Administration, State Unemployment Insurance and Employment Service Operations, https://www.dol.gov/sites/ dolgov/files/general/budget/2024/CBJ-2024-V1-07.pdf (hereinafter “FY24 SUIESO Chapter”). 52 For an overview of current funding for UI administration, see CRS In Focus IF10838, Funding the State Administration of Unemployment Compensation (UC) Benefits. 53 FY24 SUIESO Chapter, Page 23, available at https://www.dol.gov/sites/dolgov/files/general/budget/2024/CBJ-2024- V1-07.pdf#page=27. 54 One way that states can ensure that UI benefits are correctly paid to eligible individuals in a timely manner is by accessing available data sources to match claimant information with eligibility-related characteristics. States are (continued...) Unemployment Insurance: Legislative Issues in the 118th Congress Congressional Research Service 13 • required states to disclose information to the DOL Office of the Inspector General (DOL-OIG) in order to streamline DOL-OIG’s ability to conduct audits and investigations in the UI program; this includes authorizing DOL-OIG to have direct access to the Interstate Connection Network (ICON), which is used for the electronic transmission of interstate claims, as well as the IDH system, which is used in cross matching UI claimants against other databases to prevent and detect fraud and improper payments;55 • allowed the DOL Secretary to require a portion of a state’s administrative grant to be used to correct failing performance and/or have the state participate in required technical assistance activities offered by DOL;56 • authorized states to retain up to 5% of recovered fraudulent UI overpayments for program integrity use;57 • required states to use penalty and interest collections solely for UI administration;58 • provided states the authority to issue a formal warning when claimants do not clearly meet the work search requirements;59 and • allowed states to use contract support in recovery efforts under the Treasury Offset Program (TOP).60 President’s Budget Proposal for FY2025 As in FY2024, the President’s Budget Proposal for FY2025 budget request includes the same reform proposals intended to improve the administration and integrity of the UI program (see the section on “Proposed Program Integrity Legislation”).61 currently required, via DOL program guidance, to use the National Directory of New Hires (NDNH) to make sure, for instance, that UI claimants have not returned to work (for permanent-law UI programs, see DOL, ETA, “National Effort to Reduce Improper Payments in the Unemployment Insurance (UI) Program,” UIPL No. 19-11, June 10, 2011, https://wdr.doleta.gov/directives/attach/UIPL/UIPL19-11.pdf; and DOL, ETA, “National Directory of New Hires (NDNH) and State Directory of New Hires (SDNH) Guidance and Best Practices,” UIPL No. 13-19, June 17, 2019, https://wdr.doleta.gov/directives/attach/UIPL/UIPL_13-19.pdf). Currently, there is no statutory requirement for states to use NDNH or several other related data cross matches. 55 For background on recent DOL-OIG challenges related to direct access to state UI data, see the section on “Data Access” at https://www.oig.dol.gov/doloiguioversightwork.htm. 56 For an overview of the federal funding of state UI administration, see CRS In Focus IF10838, Funding the State Administration of Unemployment Compensation (UC) Benefits. 57 For an overview of UI fraud recovery issues, see CRS Insight IN12127, Unemployment Insurance Overpayment and Fraud Recovery and H.R. 1163. 58 In some situations, states apply fines and civil penalties when fraud is involved with UI benefit overpayments. See DOL, 2022 Comparison of State Unemployment Insurance Laws, Table 6-3, https://oui.doleta.gov/unemploy/pdf/ uilawcompar/2022/overpayments.pdf#page=6. 59 Under federal law (SSA §303(a)(12)), each state’s UI laws must require that individuals be able to work, available for work, and actively seeking work, as a condition of benefit eligibility, among other requirements. 60 Under federal law (SSA §303(m)), states must recover UI overpayments due to fraud and to misreported work from an individual’s federal income tax refund through the TOP. States may use contractors for recovery of SUTA debts but are prohibited from using contractors for recovery of UC and EB payments. For details, see DOL, ETA, “Recovery of Certain Unemployment Compensation Debts under the Treasury Offset Program,” UIPL 02-19, December 12, 2018, https://www.dol.gov/agencies/eta/advisories/unemployment-insurance-program-letter-no-02-19. 61 DOL, Fiscal 2025 Budget, Volume 1: FY2024 Congressional Budget Justification, Employment and Training (continued...) Unemployment Insurance: Legislative Issues in the 118th Congress Congressional Research Service 14 The FY2025 budget request includes $3.4 billion for administration of the UI system.62 This amount is $84 million less than the FY2024 budget request, but $280 million more that the FY2024 enacted appropriation of $3.1 billion.63 The budget request also includes $388 million in funding for RESEA and proposes changes to the distribution formula for RESEA grants to states. Separately, the budget would also request a fifth installment of $6 million to modernize critical information technology infrastructure essential to the states’ administration of the UI program and $25 million to fund the national identity verification offering that the Department launched to help states combat identity fraud in the UI system. Laws Enacted in the 118th Congress This section provides summary information on the one piece of legislation with UI provisions enacted in the 118th Congress, at the time of this report. P.L. 118-5, the Fiscal Responsibility Act of 2023 The Fiscal Responsibility Act of 2023 (FRA; P.L. 118-5; June 3, 2023) included three provisions that (1) rescinded specified amounts of unobligated UI administrative funding made available by the American Rescue Plan Act of 2021 (ARPA; P.L. 117-2; March 11, 2021), (2) effectively reduced budgetary adjustments to discretionary spending limits for Reemployment Services and Eligibility Assessments, and (3) rescinded all unobligated funds for Short-Time Compensation grants created under the Coronavirus Aid, Relief, and Economic Security Act (CARES Act; P.L. 116-136; March 27, 2020). ARPA provided $2 billion in additional UI administrative funding to the U.S. DOL in FY2021 to “detect and prevent fraud, promote equitable access, and ensure the timely payment of benefits.” This funding was made available until expended and can be used for (1) federal administrative costs, (2) system-wide infrastructure, and (3) grants to states and territories administering all UI benefits for program integrity and fraud prevention purposes, including for identity verification and faster claims processing.

Your answer must be drawn from the context block provided, only. You are prohibited from using other sources or drawing from prior knowledge. Provide a brief, bolded heading for your response that gives context. The body of the answer should be no longer than 200 words. What new requirements for states would the proposed FY2024 legislation create? Unemployment Insurance: Legislative Issues in the 118th Congress Congressional Research Service 12 President’s Budget Proposal for FY2024 The FY2024 budget request included several provisions intended to improve the administration and integrity of the UI program.51 These provisions included updating the factors used in determining administrative funding levels, a package of integrity-focused provisions, funding to continue to address fraud and IT modernization within the UI system, and additional funding to continue to build and support the UI Integrity Center’s Integrity Data Hub (IDH) cross-match systems. It also included an additional, broader package of proposed reforms to address systemic fraud such as identity theft and other fraud in the UI program, increase funding for the COVID-19 Fraud Strike Force Teams, and provide additional funding for Inspectors General (including the DOL Inspector General). Proposed UI Program Administrative Funding The FY2024 budget request included $3.5 billion for administration of the UI system, which was an increase over the FY2023 budget request amount of $3.1 billion.52 This amount included almost $3.0 billion “reflecting the Administration’s economic assumptions and updated workload- processing and salary factors” to administer UI.53 Additionally, the budget request for UI administration included $550 million in funding for RESEA. Separately, the budget request would have provided a fourth installment of $6 million to modernize IT infrastructure and would also have provided $150 million for program integrity purposes, including state grants to reduce fraud through identity verification services and other IT infrastructure improvements. The President’s budget proposal for FY2024 also proposed an alteration to the formula that determines the federal appropriation for state UI administration, which would have been the first substantive update in decades. Specifically, this proposal would have updated assumptions related to UI claims processing and state UI workforce salary rates, as prior assumptions for these factors were not capturing current administrative costs in states. Proposed Program Integrity Legislation The President’s FY2024 budget request also recommended a package of legislative changes to improve UI program integrity and to provide additional funding to states to help ensure proper UI payments. These proposals would have • codifed the requirement for states to data match with the National Directory of New Hires (NDNH; administered by the Department of Health and Human Services) and the Prisoner Update Processing System (PUPS, administered by the Social Security Administration) to help ensure that UI benefits are correctly paid to eligible individuals in a timely manner;54 51 DOL, Fiscal 2024 Budget, Volume 1: FY2024 Congressional Budget Justification, Employment and Training Administration, State Unemployment Insurance and Employment Service Operations, https://www.dol.gov/sites/ dolgov/files/general/budget/2024/CBJ-2024-V1-07.pdf (hereinafter “FY24 SUIESO Chapter”). 52 For an overview of current funding for UI administration, see CRS In Focus IF10838, Funding the State Administration of Unemployment Compensation (UC) Benefits. 53 FY24 SUIESO Chapter, Page 23, available at https://www.dol.gov/sites/dolgov/files/general/budget/2024/CBJ-2024- V1-07.pdf#page=27. 54 One way that states can ensure that UI benefits are correctly paid to eligible individuals in a timely manner is by accessing available data sources to match claimant information with eligibility-related characteristics. States are (continued...) Unemployment Insurance: Legislative Issues in the 118th Congress Congressional Research Service 13 • required states to disclose information to the DOL Office of the Inspector General (DOL-OIG) in order to streamline DOL-OIG’s ability to conduct audits and investigations in the UI program; this includes authorizing DOL-OIG to have direct access to the Interstate Connection Network (ICON), which is used for the electronic transmission of interstate claims, as well as the IDH system, which is used in cross matching UI claimants against other databases to prevent and detect fraud and improper payments;55 • allowed the DOL Secretary to require a portion of a state’s administrative grant to be used to correct failing performance and/or have the state participate in required technical assistance activities offered by DOL;56 • authorized states to retain up to 5% of recovered fraudulent UI overpayments for program integrity use;57 • required states to use penalty and interest collections solely for UI administration;58 • provided states the authority to issue a formal warning when claimants do not clearly meet the work search requirements;59 and • allowed states to use contract support in recovery efforts under the Treasury Offset Program (TOP).60 President’s Budget Proposal for FY2025 As in FY2024, the President’s Budget Proposal for FY2025 budget request includes the same reform proposals intended to improve the administration and integrity of the UI program (see the section on “Proposed Program Integrity Legislation”).61 currently required, via DOL program guidance, to use the National Directory of New Hires (NDNH) to make sure, for instance, that UI claimants have not returned to work (for permanent-law UI programs, see DOL, ETA, “National Effort to Reduce Improper Payments in the Unemployment Insurance (UI) Program,” UIPL No. 19-11, June 10, 2011, https://wdr.doleta.gov/directives/attach/UIPL/UIPL19-11.pdf; and DOL, ETA, “National Directory of New Hires (NDNH) and State Directory of New Hires (SDNH) Guidance and Best Practices,” UIPL No. 13-19, June 17, 2019, https://wdr.doleta.gov/directives/attach/UIPL/UIPL_13-19.pdf). Currently, there is no statutory requirement for states to use NDNH or several other related data cross matches. 55 For background on recent DOL-OIG challenges related to direct access to state UI data, see the section on “Data Access” at https://www.oig.dol.gov/doloiguioversightwork.htm. 56 For an overview of the federal funding of state UI administration, see CRS In Focus IF10838, Funding the State Administration of Unemployment Compensation (UC) Benefits. 57 For an overview of UI fraud recovery issues, see CRS Insight IN12127, Unemployment Insurance Overpayment and Fraud Recovery and H.R. 1163. 58 In some situations, states apply fines and civil penalties when fraud is involved with UI benefit overpayments. See DOL, 2022 Comparison of State Unemployment Insurance Laws, Table 6-3, https://oui.doleta.gov/unemploy/pdf/ uilawcompar/2022/overpayments.pdf#page=6. 59 Under federal law (SSA §303(a)(12)), each state’s UI laws must require that individuals be able to work, available for work, and actively seeking work, as a condition of benefit eligibility, among other requirements. 60 Under federal law (SSA §303(m)), states must recover UI overpayments due to fraud and to misreported work from an individual’s federal income tax refund through the TOP. States may use contractors for recovery of SUTA debts but are prohibited from using contractors for recovery of UC and EB payments. For details, see DOL, ETA, “Recovery of Certain Unemployment Compensation Debts under the Treasury Offset Program,” UIPL 02-19, December 12, 2018, https://www.dol.gov/agencies/eta/advisories/unemployment-insurance-program-letter-no-02-19. 61 DOL, Fiscal 2025 Budget, Volume 1: FY2024 Congressional Budget Justification, Employment and Training (continued...) Unemployment Insurance: Legislative Issues in the 118th Congress Congressional Research Service 14 The FY2025 budget request includes $3.4 billion for administration of the UI system.62 This amount is $84 million less than the FY2024 budget request, but $280 million more that the FY2024 enacted appropriation of $3.1 billion.63 The budget request also includes $388 million in funding for RESEA and proposes changes to the distribution formula for RESEA grants to states. Separately, the budget would also request a fifth installment of $6 million to modernize critical information technology infrastructure essential to the states’ administration of the UI program and $25 million to fund the national identity verification offering that the Department launched to help states combat identity fraud in the UI system. Laws Enacted in the 118th Congress This section provides summary information on the one piece of legislation with UI provisions enacted in the 118th Congress, at the time of this report. P.L. 118-5, the Fiscal Responsibility Act of 2023 The Fiscal Responsibility Act of 2023 (FRA; P.L. 118-5; June 3, 2023) included three provisions that (1) rescinded specified amounts of unobligated UI administrative funding made available by the American Rescue Plan Act of 2021 (ARPA; P.L. 117-2; March 11, 2021), (2) effectively reduced budgetary adjustments to discretionary spending limits for Reemployment Services and Eligibility Assessments, and (3) rescinded all unobligated funds for Short-Time Compensation grants created under the Coronavirus Aid, Relief, and Economic Security Act (CARES Act; P.L. 116-136; March 27, 2020). ARPA provided $2 billion in additional UI administrative funding to the U.S. DOL in FY2021 to “detect and prevent fraud, promote equitable access, and ensure the timely payment of benefits.” This funding was made available until expended and can be used for (1) federal administrative costs, (2) system-wide infrastructure, and (3) grants to states and territories administering all UI benefits for program integrity and fraud prevention purposes, including for identity verification and faster claims processing.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Summarize Section 1 in simple terms with a bullet point for each paragraph. Exclude the paragraph about the history of the section, and limit each bullet point to 30 words or less. Then, explain the importance of a pre-kindergarten program.

SECTION 1. Public education.— (a) The education of children is a fundamental value of the people of the State of Florida. It is, therefore, a paramount duty of the state to make adequate provision for the education of all children residing within its borders. Adequate provision shall be made by law for a uniform, efficient, safe, secure, and high quality system of free public schools that allows students to obtain a high quality education and for the establishment, maintenance, and operation of institutions of higher learning and other public education programs that the needs of the people may require. To assure that children attending public schools obtain a high quality education, the legislature shall make adequate provision to ensure that, by the beginning of the 2010 school year, there are a sufficient number of classrooms so that: (1) The maximum number of students who are assigned to each teacher who is teaching in public school classrooms for prekindergarten through grade 3 does not exceed 18 students; (2) The maximum number of students who are assigned to each teacher who is teaching in public school classrooms for grades 4 through 8 does not exceed 22 students; and (3) The maximum number of students who are assigned to each teacher who is teaching in public school classrooms for grades 9 through 12 does not exceed 25 students. The class size requirements of this subsection do not apply to extracurricular classes. Payment of the costs associated with reducing class size to meet these requirements is the responsibility of the state and not of local schools districts. Beginning with the 2003-2004 fiscal year, the legislature shall provide sufficient funds to reduce the average number of students in each classroom by at least two students per year until the maximum number of students per classroom does not exceed the requirements of this subsection. (b) Every four-year old child in Florida shall be provided by the State a high quality pre-kindergarten learning opportunity in the form of an early childhood development and education program which shall be voluntary, high quality, free, and delivered according to professionally accepted standards. An early childhood development and education program means an organized program designed to address and enhance each child’s ability to make age appropriate progress in an appropriate range of settings in the development of language and cognitive capabilities and emotional, social, regulatory and moral capacities through education in basic skills and such other skills as the Legislature may determine to be appropriate. (c) The early childhood education and development programs provided by reason of subparagraph (b) shall be implemented no later than the beginning of the 2005 school year through funds generated in addition to those used for existing education, health, and development programs. Existing education, health, and development programs are those funded by the State as of January 1, 2002 that provided for child or adult education, health care, or development. History.—Am. proposed by Constitution Revision Commission, Revision No. 6, 1998, filed with the Secretary of State May 5, 1998; adopted 1998; Ams. by Initiative Petitions filed with the Secretary of State April 13, 2001, and January 25, 2002; adopted 2002. SECTION 2. State board of education.—The state board of education shall be a body corporate and have such supervision of the system of free public education as is provided by law. The state board of education shall consist of seven members appointed by the governor to staggered 4-year terms, subject to confirmation by the senate. The state board of education shall appoint the commissioner of education. History.—Am. proposed by Constitution Revision Commission, Revision No. 8, 1998, filed with the Secretary of State May 5, 1998; adopted 1998. SECTION 3. Terms of appointive board members.—Members of any appointive board dealing with education may serve terms in excess of four years as provided by law. SECTION 4. School districts; school boards.— (a) Each county shall constitute a school district; provided, two or more contiguous counties, upon vote of the electors of each county pursuant to law, may be combined into one school district. In each school district there shall be a school board composed of five or more members chosen by vote of the electors in a nonpartisan election for appropriately staggered terms of four years, as provided by law. (b) The school board shall operate, control and supervise all free public schools within the school district and determine the rate of school district taxes within the limits prescribed herein. Two or more school districts may operate and finance joint educational programs. History.—Am. proposed by Constitution Revision Commission, Revision No. 11, 1998, filed with the Secretary of State May 5, 1998; adopted 1998. SECTION 5. Superintendent of schools.—In each school district there shall be a superintendent of schools who shall be elected at the general election in each year the number of which is a multiple of four for a term of four years; or, when provided by resolution of the district school board, or by special law, approved by vote of the electors, the district school superintendent in any school district shall be employed by the district school board as provided by general law. The resolution or special law may be rescinded or repealed by either procedure after four years. History.—Am. proposed by Constitution Revision Commission, Revision No. 13, 1998, filed with the Secretary of State May 5, 1998; adopted 1998. SECTION 6. State school fund.—The income derived from the state school fund shall, and the principal of the fund may, be appropriated, but only to the support and maintenance of free public schools. SECTION 7. State University System.— (a) PURPOSES. In order to achieve excellence through teaching students, advancing research and providing public service for the benefit of Florida’s citizens, their communities and economies, the people hereby establish a system of governance for the state university system of Florida. (b) STATE UNIVERSITY SYSTEM. There shall be a single state university system comprised of all public universities. A board of trustees shall administer each public university and a board of governors shall govern the state university system. (c) LOCAL BOARDS OF TRUSTEES. Each local constituent university shall be administered by a board of trustees consisting of thirteen members dedicated to the purposes of the state university system. The board of governors shall establish the powers and duties of the boards of trustees. Each board of trustees shall consist of six citizen members appointed by the governor and five citizen members appointed by the board of governors. The appointed members shall be confirmed by the senate and serve staggered terms of five years as provided by law. The chair of the faculty senate, or the equivalent, and the president of the student body of the university shall also be members.

[question] Summarize Section 1 in simple terms with a bullet point for each paragraph. Exclude the paragraph about the history of the section, and limit each bullet point to 30 words or less. Then, explain the importance of a pre-kindergarten program. ===================== [text] SECTION 1. Public education.— (a) The education of children is a fundamental value of the people of the State of Florida. It is, therefore, a paramount duty of the state to make adequate provision for the education of all children residing within its borders. Adequate provision shall be made by law for a uniform, efficient, safe, secure, and high quality system of free public schools that allows students to obtain a high quality education and for the establishment, maintenance, and operation of institutions of higher learning and other public education programs that the needs of the people may require. To assure that children attending public schools obtain a high quality education, the legislature shall make adequate provision to ensure that, by the beginning of the 2010 school year, there are a sufficient number of classrooms so that: (1) The maximum number of students who are assigned to each teacher who is teaching in public school classrooms for prekindergarten through grade 3 does not exceed 18 students; (2) The maximum number of students who are assigned to each teacher who is teaching in public school classrooms for grades 4 through 8 does not exceed 22 students; and (3) The maximum number of students who are assigned to each teacher who is teaching in public school classrooms for grades 9 through 12 does not exceed 25 students. The class size requirements of this subsection do not apply to extracurricular classes. Payment of the costs associated with reducing class size to meet these requirements is the responsibility of the state and not of local schools districts. Beginning with the 2003-2004 fiscal year, the legislature shall provide sufficient funds to reduce the average number of students in each classroom by at least two students per year until the maximum number of students per classroom does not exceed the requirements of this subsection. (b) Every four-year old child in Florida shall be provided by the State a high quality pre-kindergarten learning opportunity in the form of an early childhood development and education program which shall be voluntary, high quality, free, and delivered according to professionally accepted standards. An early childhood development and education program means an organized program designed to address and enhance each child’s ability to make age appropriate progress in an appropriate range of settings in the development of language and cognitive capabilities and emotional, social, regulatory and moral capacities through education in basic skills and such other skills as the Legislature may determine to be appropriate. (c) The early childhood education and development programs provided by reason of subparagraph (b) shall be implemented no later than the beginning of the 2005 school year through funds generated in addition to those used for existing education, health, and development programs. Existing education, health, and development programs are those funded by the State as of January 1, 2002 that provided for child or adult education, health care, or development. History.—Am. proposed by Constitution Revision Commission, Revision No. 6, 1998, filed with the Secretary of State May 5, 1998; adopted 1998; Ams. by Initiative Petitions filed with the Secretary of State April 13, 2001, and January 25, 2002; adopted 2002. SECTION 2. State board of education.—The state board of education shall be a body corporate and have such supervision of the system of free public education as is provided by law. The state board of education shall consist of seven members appointed by the governor to staggered 4-year terms, subject to confirmation by the senate. The state board of education shall appoint the commissioner of education. History.—Am. proposed by Constitution Revision Commission, Revision No. 8, 1998, filed with the Secretary of State May 5, 1998; adopted 1998. SECTION 3. Terms of appointive board members.—Members of any appointive board dealing with education may serve terms in excess of four years as provided by law. SECTION 4. School districts; school boards.— (a) Each county shall constitute a school district; provided, two or more contiguous counties, upon vote of the electors of each county pursuant to law, may be combined into one school district. In each school district there shall be a school board composed of five or more members chosen by vote of the electors in a nonpartisan election for appropriately staggered terms of four years, as provided by law. (b) The school board shall operate, control and supervise all free public schools within the school district and determine the rate of school district taxes within the limits prescribed herein. Two or more school districts may operate and finance joint educational programs. History.—Am. proposed by Constitution Revision Commission, Revision No. 11, 1998, filed with the Secretary of State May 5, 1998; adopted 1998. SECTION 5. Superintendent of schools.—In each school district there shall be a superintendent of schools who shall be elected at the general election in each year the number of which is a multiple of four for a term of four years; or, when provided by resolution of the district school board, or by special law, approved by vote of the electors, the district school superintendent in any school district shall be employed by the district school board as provided by general law. The resolution or special law may be rescinded or repealed by either procedure after four years. History.—Am. proposed by Constitution Revision Commission, Revision No. 13, 1998, filed with the Secretary of State May 5, 1998; adopted 1998. SECTION 6. State school fund.—The income derived from the state school fund shall, and the principal of the fund may, be appropriated, but only to the support and maintenance of free public schools. SECTION 7. State University System.— (a) PURPOSES. In order to achieve excellence through teaching students, advancing research and providing public service for the benefit of Florida’s citizens, their communities and economies, the people hereby establish a system of governance for the state university system of Florida. (b) STATE UNIVERSITY SYSTEM. There shall be a single state university system comprised of all public universities. A board of trustees shall administer each public university and a board of governors shall govern the state university system. (c) LOCAL BOARDS OF TRUSTEES. Each local constituent university shall be administered by a board of trustees consisting of thirteen members dedicated to the purposes of the state university system. The board of governors shall establish the powers and duties of the boards of trustees. Each board of trustees shall consist of six citizen members appointed by the governor and five citizen members appointed by the board of governors. The appointed members shall be confirmed by the senate and serve staggered terms of five years as provided by law. The chair of the faculty senate, or the equivalent, and the president of the student body of the university shall also be members. https://www.flsenate.gov/Laws/Constitution#A9 ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Answer in paragraph format. Only use the context provided for your answer.

What factors led to Temu's success?

THE RISE OF TEMU: A Shopping App Revolutionizing the Retail Experience Introduction In recent years, the retail industry has witnessed a significant shift towards online shopping. The emergence of E-commerce platforms has transformed the way consumers shop, providing convenience and access to a wide range of products. This case study explores the rise of Temu, a shopping app that has disrupted the traditional retail landscape and revolutionized the shopping experience for millions of users. Temu, a rising star in the world of online shopping, offers a vast array of fashion products, beauty items, and home goods. This Chinese-owned digital marketplace has quickly become the top free shopping app, outshining giants like Shein, Amazon, and Walmart. Temu’s business model connects customers directly to suppliers. By forging strong relationships with retailers, they’ve managed to keep prices low and maintain a vast network of suppliers. At the core of Temu’s rapid growth and competitive pricing is their innovative Next-Gen Manufacturing (NGM) model. Launched in September 2022, this Boston-based e-commerce platform serves markets in the US, Canada, Australia, and New Zealand. The NGM model revolutionizes the retail process by enabling manufacturers to produce merchandise with more precision, reducing unsold inventory and waste. However customers do complain about longer delivery times. It is unknown to what extent this is a result of the NGM model. By connecting shoppers directly with manufacturers and offering real-time insights, Temu is able to cut warehousing and transportation costs, resulting in savings of at least 50% compared to traditional processes. This cost-saving approach allows the company to offer near-wholesale prices, as they remove hidden costs and focus on accurately forecasting sales and demand. While Temu.com is gaining popularity, it faces stiff competition from other Chinese online wholesale stores like AliExpress, DHGate, Banggood, and DealExtreme. These platforms offer a wide range of products at competitive prices, along with diverse shipping options and payment methods. However, Temu stands out with its NGM model, which empowers manufacturers to create customized products. The increased visibility of demand and supply accelerates distribution and eliminates the need for large warehouses. Another distinguishing factor of Temu is its claims on sustainability and social responsibility. The NGM model promotes a more sustainable e-commerce landscape by enabling manufacturers to produce merchandise that fits the needs of consumers, leading to lower unsold inventory and waste. Significance of Temu’s Innovative approach to Shopping In the rapidly evolving world of e-commerce, convenience and speed have become the pillars on which success is built. As consumers increasingly turn to online shopping to meet their needs, the demand for faster shopping times has never been higher. Enter TEMU, the innovative new ecommerce platform that promises to redefine the shopping experience with lightning-fast shipping. TEMU's shopping prowess to traditional e-commerce platforms, makes it stand out and elevates the shopping journey for customers. Speed of Delivery: One of the most glaring advantages TEMU brings to the table is its lightning-fast shipping times. Unlike traditional platforms that often offer standard shipping that can take days or even weeks, TEMU has set a new standard with its express delivery options. With strategically located warehouses and a streamlined logistics network, TEMU ensures that customers receive their orders in record time, sometimes as soon as within a few hours of placing an order. This kind of speed sets TEMU apart from traditional e-commerce platforms, where delays in processing and shipping can often lead to frustration and disappointment for customers. Inventory Management: TEMU's commitment to swift delivery is closely tied to its advanced inventory management system. Traditional platforms often struggle to keep up with the demand, leading to instances where popular items are out of stock or on backorder. TEMU's innovative approach utilizes real-time data analytics to predict customer demands and stock products accordingly. This approach significantly reduces the chances of running out of stock, thus ensuring that customers can find what they want when they want it. Customer Satisfaction: In the world of e-commerce, customer satisfaction is paramount. TEMU's emphasis on fast shipping addresses one of the most common pain points for online shoppers – the waiting game. Traditional platforms often face challenges in providing consistent shipping times, leading to varied customer experiences. TEMU's commitment to speedy delivery contributes to higher levels of customer satisfaction by providing a more reliable and predictable shopping experience. Competitive Edge: As e-commerce continues to grow, the market becomes increasingly saturated with both established giants and new entrants. TEMU's focus on faster shipping times gives it a distinct competitive edge. It appeals to consumers who prioritize efficiency and convenience in their shopping experience. In contrast, traditional platforms may find themselves having to adapt quickly or risk losing customers to the allure of TEMU's swiffer service. Sustainability and Environmental Impact: While speed is a significant selling point for TEMU, it's essential to consider the environmental impact of such rapid shipping. Expedited shipping often requires additional resources, such as expedited transportation and packaging materials. Traditional platforms might adopt more sustainable shipping practices, such as grouping orders or optimizing delivery routes to reduce their carbon footprint. TEMU must balance its commitment to speed with environmental responsibility to ensure a positive long-term impact. Brief Overview of Temu Temu (pronounced ‘tee-moo’) is a Boston-based online marketplace founded by Pinduoduo’s parent company PDD Holding. Its business model is likened to Chinese shopping platforms SHEIN, Wish, and Alibaba – which are based on the sale of large quantities of products at prices that are so low they are almost unbelievable. Temu was founded in the USA in 2022 and is a subsidiary of PDD Holdings Inc., which is listed on Nasdaq and headquartered in Shanghai. Temu operates as an online marketplace similar to AliExpress, Walmart, and Wish, focusing on offering affordable goods. Temu allows Chinese vendors to sell to shoppers and ship directly to them without having to store products in U.S. warehouses.The company acts as an intermediary between sellers (primarily from China) and buyers without maintaining its own inventory. Temu promotes social commerce, encouraging potential buyers to find more buyers to avail discounts. The app employs gamification to engage customers and offers free shipping by circumventing customs duties. The platform allows suppliers based in China to sell and ship directly to customers without having to rely on warehouses in the destination countries . Online purchases on Temu can be made using a web browser or via a dedicated mobile application.Temu offers free products to some users which encourage new people to install the app through affiliate codes, social media and gamification. It also uses online advertising on Facebook and Instagram and many online platforms. The Temu platform went live for the first time in the United States in September 2022 and in February 2023, Temu was launched in Canada. That same month, the company aired a Super Bowl commercial advert . In March 2023, Temu was launched in Australia and New Zealand. The following month, Temu was launched in France , Italy , Germany , the Netherlands , Spain and the United Kingdom. Naturally, the prices charged by the site defy all competition (sneakers for €11, manicure kit for less than €5, phone holder for €1.80, etc.), so much so that the platform has adopted an eloquent slogan: “Buy like a Billionaire”. As the specialist in Chinese digital companies Jeffrey Towson explains to Le Monde, the platform does not yet make a margin, in order to establish itself quickly in the targeted countries. At the end of 2022, the Temu application became the most downloaded application in the United States. The TEMU (Shop Like a Millionaire) Shopping app is now boasting over 100 million Downloads on PlayStore and AppStore with over 4.7 Million reviews and about 12+ Ratings. Three months after its launch in the United States, the application was at the top of downloads. In the European Union, where the platform arrived in April (in France, the United Kingdom, Italy, the Netherlands, Spain and Germany), the success is similar. In recent days, it has been the most downloaded application in France on iOS and Android. As of April 2023, the app has been downloaded 10 million times since its launch in September 2022 and it is currently available in around 100 countries. Temu’s wide range of products is particularly appealing to consumers, combined with a gamified online shopping experience that encourages customers to try their luck and buy more and more. With its impressive growth and distinct strategy, Temu’s business model warrants a closer look. Key Factors that contributed to its initial success Leveraging the power of mobile technology, Temu aimed to bridge the gap between online and offline retail, offering a unique platform that combined the benefits of both worlds. It introduced several innovative features for better customer experience that set it apart from competitors and propelled its rapid rise to popularity. These Key Features and Functionality are; Augmented Reality (AR) Shopping: Temu integrated AR technology into its app, allowing users to virtually try on clothing, visualize furniture in their homes, and experience products before making a purchase. This feature enhanced the shopping experience and reduced the need for physical store visits. Personalized Recommendations: Temu leveraged artificial intelligence and machine learning algorithms to analyze user preferences, browsing history, and purchase behavior. Based on these insights, the app provided personalized product recommendations to users, leading to higher customer satisfaction and increased sales.Certainly! Temu's personalized recommendations were generated through a combination of artificial intelligence (AI) and machine learning algorithms. Here's an overview of how the feature worked: Data Collection: Temu collected vast amounts of user data to understand individual preferences and behavior. This data included user interactions within the app, such as product searches, views, clicks, and purchases, as well as demographic information and user-provided preferences. Data Processing and Analysis: The collected data was processed and analyzed using AI and machine learning algorithms. These algorithms examined patterns, correlations, and relationships within the data to identify user preferences, interests, and buying patterns. User Profiling: Based on the analysis, Temu created user profiles that encompassed various attributes, such as preferred product categories, brands, price ranges, and style preferences. The profiles were continually updated and refined as new data was collected and analyzed. Collaborative Filtering: One common technique used by Temu was collaborative filtering. This approach compares a user's profile with the profiles of other similar users to identify products or items that users with similar preferences enjoyed or purchased. By finding similarities between users, collaborative filtering could suggest relevant products to a particular user based on the preferences of users with similar tastes. Content-Based Filtering: Another technique employed by Temu was content-based filtering. This method focused on the characteristics and attributes of products themselves. It analyzed product descriptions, features, tags, and other metadata to identify similarities and correlations between products. For example, if a user showed a preference for certain brands or specific features, content-based filtering could recommend similar products that match those preferences. Machine Learning and Iterative Refinement: Temu's algorithms continuously learned and improved over time. As users interacted with the app and provided feedback, the algorithms adjusted their recommendations based on the user's responses and behavior. Machine learning techniques enabled the system to adapt and refine its recommendations based on real-time user feedback. Real-Time Contextual Factors: In addition to user preferences, Temu also considered real-time contextual factors, such as trending products, seasonal trends, and popular items in the user's location. These factors were incorporated into the recommendation algorithms to ensure up-to-date and relevant suggestions. By leveraging AI, machine learning, and user data, Temu's personalized recommendation system aimed to understand each user's unique preferences and deliver tailored product suggestions. The algorithms continually evolved to provide increasingly accurate and relevant recommendations, enhancing the user experience and facilitating personalized shopping journeys. Social Commerce Integration: Recognizing the power of social media, Temu incorporated social commerce features, enabling users to share products, create wish lists, and seek recommendations from friends and influencers. This integration expanded Temu's reach and facilitated organic growth through user-generated content. Seamless Checkout and Delivery: Temu prioritized a frictionless shopping experience by streamlining the checkout process and offering multiple secure payment options. Additionally, it partnered with reliable logistics providers to ensure prompt and efficient product delivery, enhancing customer satisfaction and loyalty. Seamless Checkout and Payment Options: Temu focused on streamlining the checkout process to provide a seamless and hassle-free experience for users. It offered multiple secure payment options, including credit/debit cards, mobile wallets, and payment gateways, allowing users to choose their preferred method. This flexibility and ease of payment contributed to a smoother transaction process and reduced cart abandonment rates.Temu implemented several measures to ensure the security of payment options for its users; Secure Payment Gateways: Temu has partnered with trusted and secure payment gateways to handle the processing of user payments. These payment gateways employ robust security measures such as encryption, tokenization, and secure socket layer (SSL) protocols to protect sensitive payment information during transmission. Encryption: Temu has implemented encryption protocols to safeguard user payment data. This involves encrypting sensitive information such as credit card details, bank account numbers, and personal information to prevent unauthorized access or interception. Encryption ensures that even if the data is intercepted, it remains unreadable and unusable to unauthorized parties. Compliance with Payment Card Industry Data Security Standards (PCI DSS): Temu has adhered to the Payment Card Industry Data Security Standards, which are industry-wide standards established to ensure the secure handling of cardholder data. Compliance with PCI DSS involves maintaining a secure network, implementing strong access controls, regularly monitoring and testing systems, and maintaining an information security policy. Two-Factor Authentication (2FA): Temu has implemented two-factor authentication as an additional layer of security for payment transactions. This requires users to provide two forms of verification, such as a password and a unique code sent to their mobile device, to authenticate their identity before completing a payment. Fraud Detection Systems: Temu has employed fraud detection systems and algorithms to identify and prevent fraudulent payment activities. These systems analyze various factors, such as user behavior, transaction patterns, and known fraud indicators, to detect and flag suspicious transactions for further verification or intervention. Regular Security Audits: Temu has conducted regular security audits and assessments to identify vulnerabilities and ensure that all payment systems and processes meet the highest security standards. This includes conducting penetration testing, code reviews, and vulnerability scans to proactively identify and address any potential security weaknesses. User Education and Awareness: Temu has implemented user education programs to raise awareness about safe online payment practices. This could include educating users about the importance of strong passwords, avoiding phishing attempts, and regularly monitoring their payment transactions for any unauthorized activity. Order Tracking and Delivery Updates: Temu provided users with real-time order tracking and delivery updates. Users could monitor the progress of their orders and receive notifications regarding shipment status, estimated delivery time, and any delays. This feature enhanced transparency and kept users informed throughout the delivery process, improving overall customer satisfaction. User Reviews and Ratings: To facilitate informed purchasing decisions, Temu incorporated user reviews and ratings for products. Users could leave feedback and rate their purchases, helping others make well-informed choices. This feature added a layer of trust and credibility to the shopping experience and fostered a community-driven approach to product evaluation. Virtual Stylist and Fashion Advice: Temu introduced a virtual stylist feature that offered personalized fashion advice and styling tips. Users could provide information about their preferences, body type, and occasion, and receive tailored recommendations for outfits and accessories. This feature catered to users seeking fashion inspiration and guidance, enhancing their shopping experience. Temu’s Virtual Stylist feature works in the following ways; It helps Users of the Temu app to create a profile by providing information about their preferences, body type, style preferences, and any specific fashion requirements they may have. The virtual stylist feature uses algorithms and machine learning techniques to analyze the user's profile and understand their style preferences. It considers factors such as color preferences, patterns, clothing types, and previous purchases. The feature assists users in recommendations. Based on the user's profile and preferences, the virtual stylist recommends outfits, clothing items, or accessories that align with their style. These recommendations may include images, descriptions, and links to purchase the recommended items. The feature also provides style tips, fashion trends, and suggestions to help users stay updated and make informed fashion choices. It helps users in Interactive Communication. The virtual stylist often offers Interactive communication channels such as chatbots or messaging systems. Users ask questions, seek styling advice, or provide feedback to further refine the recommendations. The feature helps Integration with User Feedback,it learns and improves over time by incorporating user feedback and preferences. As users interact with the feature, their feedback and engagement help train the algorithm to provide more accurate and personalized recommendations Growth and Adoption over time Temu was ranked No. 12 in the 2022 holiday traffic, topping retailers like Kohl’s and Wayfair. With an average of 41.0 million visitors in November and December, Temu surpassed major ecommerce sites like Kohl’s, Wayfair, and Nordstrom, and was within striking distance of Macy’s. Temu surged ahead of low-price Chinese goods sellers Shein and Wish.com in dramatic fashion. Not only did Temu quickly surpass Wish.com amid its recent downswing, it also managed to leapfrog Shein’s impressive recent gains. Shein’s steady rise has the company now looking to raise capital at a reported $64 billion valuation as reported by Reuters. Wish.com, by comparison, has been hemorrhaging money and has plummeted 98% from its peak stock price, with a market cap below $400 million. Using cheap wares to attract customers can work, but profitability is a challenge when operating under tight margins. High acquisition costs can be a killer, and there will also be a need to pivot into higher-margin goods. Temu is keying on its mobile app for loyalty. Temu’s bargain-basement prices make purchases a low consideration in most cases. Its best use case is when customers realize a need (“Shoot, I left my iPhone charger at the hotel and need another one”) and can buy quickly and cheaply. The app can drive habit formation around this, and the more that shoppers rely on the app the less likely Temu will have to pay for ads to drive conversions. Temu exploded out of the gates and its rapid rise warrants attention. As something of a Wish.com clone, there’s reason to be skeptical it can find long-term profitable growth when its early stage capital eventually rationalizes. Whether Temu avoids a similar fate will come down to whether it can improve upon the Wish.com playbook to build a loyal and engaged user base and drastically reduce customer acquisition costs over time. A killer TikTok strategy and sticky mobile app was key to achieving what its predecessor could not. As originally featured in the Retail Daily newsletter, Amazon has been the most downloaded shopping app in the US for a very long time. It managed to beat local competitors like Walmart, and even international competition from apps like Wish. But with the coming of Temu it looked like Amazon had finally met its match. Going all the way back to 2020, Amazon's shopping app was averaging around 550K downloads per week in the US, according to our estimates. The summer of 2022 was strong, pushing Amazon's downloads to more than double with a range between 800K and 1.2M weekly downloads. And that spike didn't slow down until February, 2023, after which downloads really started sloping down. SHEIN, a clothing retailer that sells "fast fashion" shipped from China, has been chasing Amazon's tail since it launched. Key word being "chasing". SHEIN averaged a little over half of Amazon's downloads back in 2020. They got close a few times but not enough to really take the lead. In January of 2023, that changed and SHEIN's downloads are now about double those of Amazon in the US. SHEIN saw 617K downloads from the App Store + Google Play in the US last week, according to our estimates. And SHEIN isn't even Amazon's biggest threat right now but Temu, a China-based retailer that sells a variety of goods, from clothes to furniture, at very low prices, since its launch late last year. The holiday shopping season was big for Temu. It averaged 2M new downloads every week between November and December, according to our estimates. Downloads dropped since, which makes sense overall, but are still astronomically high in comparison. Temu saw 1.3M new downloads last week in the US. This is a big problem for Amazon which may mean the next Prime Day will be a little more exciting than the last few. And yes, Temu is one of the biggest spends on Apple Search Ads which helps it get those downloads. Challenges Addressed by Temu The traditional retail model is almost getting outdated thereby posing several challenges. While the “customer is always right” mantra has held true for quite some time, the amount of power wielded by consumers has never been higher than it is right now. Customers are no longer forced to choose between just a couple of options when looking to purchase new luxury goods. Not only has the number of retailers expanded exponentially in recent years, but so has the information available to customers. The amount of choice people enjoy today has also led to a waning of brand loyalty, with customers switching between retailers and online/in-store channels from purchase to purchase, depending which best serves their needs at the time. Luxury retailers are not immune to this trend either, as even wealthy customers now tend to shop around for the best option. This decline in brand loyalty customers presents a unique retailing problem, as retailers try to find new and innovative ways to appeal to buyers – both existing and potential; Consumers are Choosing Multichannel Buying Experiences: With more complete e-retail experiences available, and shipping times greatly reduced, it is little wonder around 96% of Americans utilize online shopping in one way or another. However, those same Americans spend about 65% of their total shopping budget in traditional brick-and-mortar locations. In other words, while almost everyone is shopping online, they are making more purchases in stores. Customers are moving seamlessly between online and offline experiences, and are open to retailers who can best facilitate these transitions. Closing the divide between online and offline retail, Temu solves some issues. It is focused on creating a second-to-none customer experience across all channels. Customers are looking for retailers they can trust to deliver exceptional service time and again. They have the right customer which has helped them to create an omnichannel customer experience for consumers to interact wherever and however they wish by incorporating real-time feedback across channels and devices – engaging the customer wherever they may be. Customers Expect a Seamless Experience: When transitioning between online and in-store experiences, customers not only want the same products to be available, they also want their experience to be seamless. This means, if they are a regular online customer, they want to be treated like a regular customer when they visit a brick-andmortar location. This is quite problematic. However, Temu has created this type of fluid online/offline experience for their customers, it has ceased pitting its channels against one another. Centralized customer data has helped it build a seamless, fluid experience beginning with an easily-accessible customer profile. Retailers lacks an outstanding Experience To Attract Customer Loyalty: Customer experience is the biggest contributor towards brand loyalty, the Traditional Retail model makes it difficult to build a good customer experience.Negative experience being the most significant factor in affecting a customer’s likelihood to make a repeat visit. Most customers also serve people in their own working lives, meaning when they are on the other side of the counter, they want to feel important.While promotions and offers can certainly contribute towards helping customers feel like they are special, the real key to an outstanding experience is personalization which the retail model falls short of. Getting to know customers from their previous purchases and interests can help retailers drive loyalty. These insights can be gleaned from data, or even a simple conversation.Temu addresses this challenge by rendering coupons, bonuses and reduced cost to existing and new customers. It is equally personalized with the user. A Siloed Marketing Infrastructure Makes It Expensive and Unwieldy to get Your Message Across; The traditional retail model features separate channels, which makes customer data to become siloed very easily. If all the moving parts of a marketing department are not communicating efficiently and working together, customers become overwhelmed with conflicting or repeated messages. This bombardment of marketing communications has easily had the opposite of the intended effect and driven customers to competitors with a clearer and more congruent message. The right technology and communication procedures can ensure all arms of a marketing team are on the same page. Temu as a modern retailer has been engaging with their customers across many different channels. From SMS, to email and social media, multi-channel communications are essential to engagement which, in turn, drives the creation of the perfect customer experience. So Many Technologies Exist to Drive Marketing and Sales, but They Don’t Seem to Work Together: While the amount of data gathered by businesses keeps growing at an alarming rate, the number of staff available to analyze it is staying more-or-less the same. What’s important, then, is making sure all this data is being used in the correct way and not contributing towards the data silo problem. This means finding a technology solution which can handle the huge amount of data being generated and ensure it is focused in a direction which best benefits rather than overwhelms marketing efforts. The data scientist approach to marketing is only going to become more prevalent as time goes on when creating a truly unified omnichannel service.Temu has ensured that all existing technologies work together which is why they get best results. Only in the combining of streamlined un-siloed data science, seamless cross-channel customer service and marketing, and authentic personalization, can traditional retailers create buyer experiences which can combat the fickle nature of the modern consumer and lead just like Temu. Strategies Implemented to Revolutionize The Retail Industry Temu adopted and implemented some strategies which accounted for its success. Temu’s business model is built around low prices. It offers even more discounts and lower prices than SHEIN, with special offers such as items sold for as little as one cent. Temu further differentiates itself by offering free shipping and returns to customers, which is made possible by PDD Holding’s extensive network of suppliers and shipping partners. An efficient logistics network is not to be underestimated, as problems with supply and distribution networks are seen as a major factor in the failure of Alibaba and Wish to break into the Western market.. Aside this, the following strategies were implemented; Combining Shopping and Entertainment: One-fifth of online shoppers in the U.S. say they miss the in-store shopping experience when they shop online. Temu aimed to bridge this gap and introduced games into the shopping process. By playing games like Fishland, Coin Spin, Card Flip, and others, customers can win rewards that ultimately lead to more time spent on the site and a dopamine rush from winning free items. To keep people playing these games, however, the app relies heavily on referrals, another core business strategy. These games were designed to be simple, addictive, rewarding, and increase user engagement and retention. According to app intelligence firm Sensor Tower, Temu’s average daily sessions per user in the US increased by 23% from October 2022 to January 2023. Some other games in Canada include scratch cards, card games, and cash games. Temu: Shared Shopping Experience: Group Buying is a familiar concept in Asia that Temu has extended to its Western customer base. Essentially, it has increased customers’ bargaining power by forming groups to share a bulk discount. This plays into the aforementioned referral program, which gives discounts to customers who bring new clients to the app and enables a shared shopping experience. Affiliate Programs and Heavy Advertising: As SHEIN had already proven effective, Temu sent free items to a large number of influencers and micro-influencers to promote Temu on YouTube and TikTok. A younger customer base of users under the age of 35 is particularly attractive to Temu, as younger consumers are typically less able and willing to pay large sums for products. Seeing a favorite internet personality or a personal acquaintance promoting the products has led to many young customers to imitate the purchase. Temu’s omnipresence on TikTok and YouTube is seen as a key factor in why this marketplace has taken off so quickly. A strong presence on TikTok and YouTube: Temu has leveraged the power of social media platforms, especially TikTok and YouTube, to spread awareness and generate buzz about its products and offers. The hashtag #temu on TikTok has amassed over 1.3 billion views, while Temu’s official YouTube account videos have grossed over 215 million views since last August. Temu’s marketing strategy relies on creating viral content that showcases its products entertainingly and engagingly, such as unboxing videos, product reviews, challenges, and giveaways. Temu also collaborates with influencers and celebrities with large followings on these platforms. Temu’s Audience: Temu’s primary target audience has been the young and price-conscious generation of online shoppers looking for bargains and discounts. According to a report by Daxue Consulting, the majority of Temu’s followers (32.68%) are aged 25-34, followed by 18-24 (28.57%) and 35-44 (21.43%). Temu appeals to these consumers by offering personalized recommendations based on their preferences and browsing history and gamified features that allow them to earn credits, gifts, and better deals by playing in-app games or inviting their friends to join the app. Referrals: A Win-Win Strategy for Users and Temu Temu has implemented a referral program encouraging users to invite friends and contacts to join the app in exchange for credits and gifts. Users can share their referral links or codes on social media platforms like Facebook, Instagram, and TikTok. For example, users can join a “Fashion Lovers” team and get $20 in credits by inviting five friends who also love fashion within 24 hours. These referrals help users save money on their purchases, help Temu acquire new customers, and expand its network of sellers. Temu’s Marketing and Growth Strategy that led to its Rise Temu's growth has been remarkable in a short period of time. It reached the top downloads in the shopping category of both Apple's App Store and Google Play and is quickly establishing itself as a high-potential and innovative player in the e-commerce industry. Its success is ultimately its low prices, unlocked by their innovative Next-Gen Manufacturing (NGM) model. It employed a multifaceted marketing strategy to drive user acquisition and brand awareness which has been working greatly for them; Influencer Collaborations: To reach a wider audience, Temu has been collaborating with popular social media influencers and celebrities who promoted the app and shared their shopping experiences. Influencers came from a wide range of individuals, including fashion bloggers, lifestyle influencers, beauty gurus, tech enthusiasts, or experts in specific product categories.This strategy generated buzz and created a sense of credibility and trust among potential users. This marketing strategy was successfully implemented through; Influencer Selection: Temu carefully identified and selected influencers who aligned with its target audience, brand values, and product offerings. These influencers typically had a strong online presence, a relevant niche or expertise, and a sizable following. Temu considered factors such as engagement rates, authenticity, and the influencer's ability to create appealing and relatable content. Exclusive Partnerships: Temu forged exclusive partnerships with influencers, often signing them as brand ambassadors or collaborators. These collaborations involved long-term commitments, where influencers actively promoted Temu's app and its features on their social media platforms, websites, or blogs. The exclusivity of these partnerships helped establish a strong association between the influencers and Temu, increasing brand loyalty and credibility. Sponsored Content: Temu engaged influencers to create sponsored content that showcased the app's features, user experience, and the benefits of using Temu for shopping. Influencers shared their personal experiences, demonstrated the app's functionalities, and highlighted the unique advantages of using Temu over other shopping platforms. This content was often shared through blog posts, social media posts, videos, and live streams. Product Reviews and Recommendations: Influencers played a crucial role in reviewing and recommending products available on Temu. They shared their honest opinions and experiences using products from various brands. Their reviews and recommendations helped build trust and credibility among their followers, encouraging them to explore and purchase products through Temu. Giveaways and Contests: Temu collaborated with influencers to host giveaways and contests, where users had the chance to win exclusive prizes or discounts by engaging with the app or participating in specific promotional activities. These initiatives created buzz, generated user excitement, and attracted new users to the platform. Affiliate Marketing: Temu employed affiliate marketing strategies with influencers, where influencers received a commission or referral fee for every user who downloaded the app or made a purchase through their unique referral links. This incentivized influencers to actively promote Temu and its offerings, as their earnings were directly tied to the success of their referrals. Event Participation: Temu partnered with influencers for events such as product launches, fashion shows, or brand campaigns. Influencers attended these events, shared live updates, and provided behind-the-scenes content to their followers, creating a sense of exclusivity and fostering excitement around Temu's activities. User-generated Content: Temu encouraged influencers and their followers to create usergenerated content related to the app. This could include unboxing videos, styling tips, or hauls showcasing products purchased through Temu. Such content served as social proof and encouraged other users to engage with the app and make purchases. Overall, Temu's collaborations with influencers helped amplify its brand message, expand its reach to new audiences, and establish credibility within the social media landscape. By leveraging the influence and creative abilities of influencers, Temu successfully tapped into their followers' trust and engagement, driving user acquisition, and fostering a positive brand image. User Referral Program: Temu has been incentivizing existing users to refer the app to their friends and family by offering discounts or exclusive rewards. This word-of-mouth marketing approach contributed to the app's exponential growth and user acquisition. Targeted Digital Advertising: Temu has been leveraging targeted digital advertising campaigns across various digital platforms like Facebook, Instagram, Twitter, TikTok and soon Telegram focusing on specific demographics and user segments. By tailoring their messaging and creative assets, Temu effectively reached potential users with personalized content. Expansion into New Markets: After gaining traction in its home market, Temu has been expanding its operations into international markets. It strategically entered regions with high smartphone penetration and a growing ecommerce ecosystem. This expansion allowed Temu to tap into a larger customer base and establish itself as a global player in the shopping app industry. Partnerships with Brands and Retailers: Recognizing the importance of strategic alliances, Temu has been forging partnerships with renowned brands and retailers. These collaborations involved exclusive product launches, limitededition collections, and promotional campaigns. By aligning with established names in the retail industry, Temu gained credibility and attracted a wider range of customers. Continuous Innovation: Temu has been prioritizing continuous innovation to stay ahead of the competition. It regularly updated its app with new features and enhancements based on user feedback and emerging trends. For example, it introduced a virtual stylist feature that offered personalized fashion advice and styling tips, further enhancing the user experience. Data-driven Insights: Temu has been leveraging the vast amount of user data it collected to gain valuable insights into consumer behavior, preferences, and trends. These insights were used to refine its product offering, improve targeted advertising efforts, and optimize the overall shopping experience. By harnessing the power of data, Temu was able to make data-informed decisions and stay attuned to evolving customer needs. Seamless Integration with Physical Stores: Recognizing the importance of the omnichannel experience, Temu has been integrating its app with physical stores. It introduced features like in-store barcode scanning, which allowed users to access product information, read reviews, and make purchases directly from their smartphones while inside partner retail locations. This integration blurred the lines between online and offline shopping and provided a seamless and unified experience. Social Impact Initiatives: Temu also has also been focusing on social impact initiatives to connect with socially conscious consumers. It launched sustainable product collections, partnered with NGOs for charitable causes, and implemented eco-friendly packaging practices. These initiatives resonated with environmentally and socially conscious users, further strengthening Temu's brand reputation and loyalty. Continuous Customer Support: Temu has been placing strong emphasis on customer support and responsiveness. It established dedicated customer service channels, including live chat support and a comprehensive FAQ section. Timely and effective customer support enhanced user satisfaction, resolved issues promptly, and fostered a positive brand image. A heavy paid media strategy: Like other well-funded internet companies, Temu appears to be spending heavily for app installs and on search ads. Search for almost any commodity product—especially if your search includes the word “cheap”—and you’re likely to find a Google result for Temu. Temu also gained attention with multiple Super Bowl spots, putting it on the map for many US consumers for the first time. Results and Impacts The rise of Temu as a shopping app has revolutionized the Retail Industry and also Consumer Experience; User Base and Revenue Growth: Within two years of its launch, Temu has amassed millions of active users and experienced exponential revenue growth. Its user-centric approach and innovative features resonated with consumers, driving adoption and usage. Enhanced Customer Experience: Temu's focus on personalization, convenience, and seamless shopping experiences has elevated customer satisfaction levels. Users appreciated the ability to try on products virtually, receive tailored recommendations, and enjoy hassle-free transactions. Disruption of Traditional Retail: The Traditional Retail industry has suffered relatively as a result of the rise of Temu as a Shopping App. It has greatly disrupted traditional brick-and-mortar retail, with many businesses. This is so because with their new innovation, they have explored other parts(online) which the traditional retailers do not have. Its rise has posed several challenges for traditional retailers as they struggle to adapt to the changing landscape; Online Presence and Digital Transformation: Traditional retailers are still struggling with establishing a strong online presence and undergoing digital transformation. Building and maintaining an effective e-commerce website or app requires technical expertise, investment in infrastructure, and a shift in mindset. Adapting to the digital realm is now very challenging for retailers who have primarily operated in brick-and-mortar stores. Competition with E-commerce Giants: E-commerce platforms like Temu with significant resources, a broad customer base, and strong brand recognition which makes it difficult for Traditional retailers to compete with in terms of pricing, product selection, and customer convenience. It can be challenging for them to match the speed, efficiency, and scale of operations offered by online marketplaces. Supply Chain and Logistics: Traditional retailers have gotten used to managing inventory primarily for physical stores and now face challenges in adapting their supply chain and logistics operations to accommodate online sales. Efficient inventory management, order fulfillment, and last-mile delivery is quite complex and requires adjustments to meet the demands of e-commerce customers. Customer Expectations and Experience: Online shoppers have come to expect a seamless and personalized shopping experience. Traditional retailers now struggle to meet these expectations, especially provided they have very limited experience in online customer engagement, personalization, and tailoring recommendations. Adapting to a customer-centric approach and providing a consistent omnichannel experience can be a significant challenge. Data and Analytics: E-commerce platforms like Temu rely heavily on data and analytics to understand customer behavior, preferences, and trends. Traditional retailers have limited experience in collecting, analyzing, and utilizing customer data effectively. Harnessing data to make data-driven decisions and optimize operations is now a significant hurdle for retailers transitioning to an online model. Operational Costs and Margins: Traditional retailers are facing financial challenges to adapt to ecommerce. Online operations require investments in technology, infrastructure, marketing, and fulfillment capabilities. Retailers need to reevaluate their pricing strategies, optimize operational costs, and find ways to maintain profitability in the face of increased competition and potentially lower margins. Brand Differentiation and Customer Loyalty: Building a strong brand and fostering customer loyalty has proven to be more challenging in the online space. Traditional retailers may have developed a loyal customer base through in-person interactions and personalized service. Translating that loyalty to the digital realm and effectively differentiating their brand from competitors needs innovative strategies and marketing efforts which will take time. By leveraging technology and understanding evolving consumer behaviors, Temu has disrupted the retail industry, reshaped shopping habits, and set new standards for convenience and engagement in the digital age; Temu’s Setbacks Despite its rapid rise, its relationship with sister company Pinduoduo has brought about several challenges in delivery of goods as compared to its competitors and other areas; According to reports published in Times, Temu is beginning to develop a reputation for undelivered packages, mysterious charges, incorrect orders and unresponsive customer service. Temu itself acknowledges that its orders take longer to arrive than those from Amazon—typically 7-15 business days as they come from “overseas warehouses.” In a series of Facebook messages with Times, Roper Malloy, a client complained of spending $178 on gifts from Temu for her family, including two drones and some makeup for her daughter which has never arrived. She said she has contacted the company several times for a refund, which has also yet to arrive. On May 17, 2023, Montana Governor Greg Gianforte banned Temu from statewide government devices, as well as ByteDance apps (including TikTok ) , Telegram , and WeChat. In June 2023, the U.S. House Select Committee on U.S.- Chinese Communist Party Strategic Competition stated that Temu did not maintain "even the facade of a meaningful compliance program" with the law. Uyghur on Forced Labor Prevention to keep goods made by forced labor off its platform. In October, the Boston branch of the Better Business Bureau opened up a file on Temu and has received 31 complaints about the website. Temu currently has a C rating on the BBB, and an average customer rating of 1.4 stars out of 5, although from only 20 reviews. (Complaints are separate from reviews, which do not factor into BBB’s official rating.) McGovern at the BBB mentioned that, it’s unusual for such a new company to receive so many complaints in such a short amount of time. Temu has acknowledged and responded to every complaint posted to the BBB website, but many of those complaints remain unresolved. Temu’s sister company, Pinduoduo, has long been accused of hosting sales of counterfeits, illegal goods, or products that do not match their descriptions. (Pinduoduo wrote in its SEC filings that it immediately removes unauthorized products or misleading information on its platform, and freezes the accounts of sellers on the site who violate its policies.) There have been no BBB complaints that allege the goods Temu ships are counterfeit or fake. Additionally, in 2021, the deaths of two Pinduoduo employees spurred investigations and boycotts over the company’s working conditions, according to the New York Times. How Temu could affect the U.S. economy In May 2023, the U.S.-China Economic and Security Review Commission raised concerns about risks to users' personal data on Temu as a shopping app affiliated with Pinduoduo, which was removed from Google Play after some of its versions were found to contain malware. Schmidt, at Vanderbilt, who specializes in security and privacy, is of the opinion that Temu’s data and privacy practices aren’t out of the ordinary; The company collects lots of personal data about users and then deploys that data to sell ads. However, he says that Temu’s rise could have a bigger impact not in terms of privacy concerns, but in terms of pressure on American companies and workers. If more and more American consumers flock to Temu to buy cut-rate goods, that could pressure Amazon and other competitors to slash their prices too which would affect wages. Areas for Improvements Despite its innovative business model and commitment to sustainability, Temu still has some areas that need improvement; Real-Time Shopping: Cost-Effectiveness vs. Plagiarism and Exploitation: Temu’s most innovative and effective strategy has been highly ambivalent and criticized. Similar to SHEIN, Temu has been using a reverse-manufacturing model that relays customer feedback directly to manufacturers. Starting off with smaller quantities that are offered on the marketplace, products in high demand are reordered, while others are replaced. According to Temu, this results in environmental efficiency because product inventory is aligned with customer demand in real time. In addition, a greater number of products can be offered than with traditional retail strategies. With this method, SHEIN was able to launch 150,000 new items in 2020, beating its competitors by a wide margin. Temu Has to Fight Criticism: Critics point to several detrimental effects of this type of 'ultra-fast' commerce: To ensure low prices, manufacturers must keep costs down, contributing to the continued poverty of workers in manufacturing countries. The same goes for product quality and environmental friendliness: Cheap products that break easily contribute to increasing amounts of waste, returned products tend to be dumped rather than recycled or resold, and the high number of new products sold is only possible by ripping off SME fashion designers and creators. TrustPilot reviews reveal a 2.9-star average, with the majority of one-star reviews citing long shipping times, low-quality items, and poor customer service. Low quality items can become a sustainability issue in itself, since those products have a higher chance of ending up in landfill. It’s essential for Temu to address these concerns and maintain a balance between low prices and customer satisfaction. Lessons Learned Temu's rise as a shopping app exemplifies the transformative power of technology in the retail industry. Its success serves as an inspiration for other businesses seeking to adapt and thrive in the digital era. Overall, the rise of Temu as a shopping app has been driven by its commitment to innovation, personalized experiences, strategic partnerships, and a customer-centric approach. The marketplace Temu has achieved impressive success with its business model of offering low-priced products and free shipping, combined with a gamified shopping experience. Temu's strategy also includes group buying, referrals, affiliate programs, and heavy advertising on social media platforms. While Temu's real-time shopping model, which involves relaying customer feedback directly to manufacturers, is seen as innovative and cost-effective, it has also garnered criticism. Critics argue that this approach can lead to environmental issues, exploitation of workers, and plagiarism of designs from small and medium-sized fashion creators. Despite these concerns, Temu's combination of low prices, gamified shopping, and heavy advertising on platforms like TikTok and YouTube has made it a major player in the ultra-fast eCommerce sector. However, Temu's most controversial strategy is its real-time shopping model akin to that of SHEIN, which relays customer feedback directly to manufacturers. While this model increases costeffectiveness and product variety, critics argue that it contributes to environmental degradation, exploitation of workers, and plagiarism of fashion designers. Nonetheless, Temu's growth and distinct strategy make it a noteworthy player in this emerging business model of ultra-fast eCommerce, and it will be interesting to see how this trend plays out in the future. Actionable Takeaways for other Businesses in the Retail Industry Traditional Retailers who wish to also rise like Temu should consider the following steps; Develop a User-Friendly E-commerce Website: Create a well-designed, intuitive, and user-friendly e-commerce website that offers a seamless shopping experience. Ensure that the website is responsive, optimized for mobile devices, and provides easy navigation, product search, and checkout processes. Emphasize Branding and Differentiation: Clearly define the brand identity and unique selling propositions of your retail business. Highlight what sets your products apart from competitors and communicate a compelling brand story to engage online customers. Use high-quality visuals and persuasive copywriting to convey your brand message effectively. Optimize for Search Engines: Implement search engine optimization (SEO) techniques to improve the visibility of your website in search engine results. Conduct keyword research to understand the terms and phrases your target audience is searching for, and optimize your website's content, meta tags, and URLs accordingly. Leverage Social Media: Use social media platforms to build an online community, engage with customers, and promote your products. Regularly post engaging content, including product updates, customer testimonials, and behind-the-scenes glimpses. Encourage user-generated content and respond promptly to customer inquiries and feedback. Invest in Digital Marketing: Develop a comprehensive digital marketing strategy that includes online advertising, email marketing, influencer collaborations, and content marketing. Target specific customer segments and utilize data-driven approaches to reach your audience effectively and drive traffic to your website. Provide Excellent Customer Service: Offer exceptional customer service across all online channels, including live chat, email, and social media. Respond promptly to customer inquiries, provide accurate product information, and address any issues or concerns in a timely manner. Personalize the customer experience as much as possible to build trust and loyalty. Implement Online Customer Engagement Tools: Incorporate tools such as live chat, product reviews, ratings, and personalized recommendations to enhance customer engagement and create a sense of interactivity on your website. Encourage customer feedback and testimonials to build social proof and credibility. Collaborate with Influencers and Online Communities: Partner with relevant influencers or online communities in your industry to extend your reach and tap into their established audiences. Engage in collaborations, product reviews, or sponsorships to increase brand visibility and credibility. Analyze and Optimize: Continuously monitor and analyze website metrics, customer behavior, and online marketing campaigns. Utilize analytics tools to gain insights into what is working and what needs improvement. Optimize your online presence based on data-driven decisions to enhance the user experience and drive conversions. Adapt to Changing Trends: Stay up to date with the latest e-commerce trends, technologies, and consumer preferences. Be willing to experiment, adapt, and embrace new technologies or platforms that can enhance your online presence and provide a competitive edge. By implementing these strategies, traditional retailers can establish a strong online presence, attract online customers, and compete effectively in the digital marketplace. It's important to continuously evaluate and refine your online presence based on customer feedback, market trends, and emerging technologies to stay ahead of the competition. Future Outlook The rise of Temu as a shopping app has been remarkable, and it has successfully disrupted the retail experience by implementing innovative strategies and business models. Looking ahead, there are several key factors that will shape the future outlook of Temu and determine its continued success in the competitive online shopping market; Expansion into New Markets: Temu has already expanded its operations to several countries, including the US, Canada, Australia, New Zealand, France, Italy, Germany, the Netherlands, Spain, and the United Kingdom. To sustain its growth, Temu will likely continue to explore opportunities for expansion into new markets, both within and outside of these regions. This expansion will allow the platform to reach a larger customer base and tap into new consumer preferences and demands. Improvement in Delivery Times: One area of concern for customers is the longer delivery times associated with Temu's Next-Gen Manufacturing (NGM) model. To address this issue, Temu may invest in optimizing its supply chain and logistics processes. By streamlining operations and partnering with efficient shipping providers, Temu can reduce delivery times and enhance the overall customer experience. Enhanced Customer Engagement: Temu's success is partly attributed to its gamification strategies and social commerce approach. To maintain customer engagement and loyalty, Temu will need to continuously innovate and introduce new features that incentivize users to stay active on the platform. This could include personalized recommendations, rewards programs, and interactive shopping experiences. Sustainability and Social Responsibility: Temu has positioned itself as a platform that promotes sustainability and social responsibility through its NGM model, which reduces unsold inventory and waste. Going forward, it will be crucial for Temu to uphold these values and communicate its commitment to sustainability to customers. This can be achieved through transparent supply chain practices, eco-friendly packaging options, and partnerships with ethical suppliers. Competition and Differentiation: While Temu has gained significant traction, it faces strong competition from other Chinese online wholesale platforms and established e-commerce giants. To stay ahead, Temu will need to continue differentiating itself through its NGM model, competitive pricing, and unique product offerings. It should also focus on building a strong brand identity and nurturing customer trust through excellent customer service and reliable purchase protection. navigate the competitive landscape. With its innovative approach and commitment to customer satisfaction, Temu has the potential to continue reshaping the online Conclusion Conclusively, Temu has emerged as a shopping app that is revolutionizing the retail experience through its Next-Gen Manufacturing model and direct-to-supplier approach. By focusing on cost savings, customization, and sustainability, Temu has gained a competitive edge in the market. With a lot of consumer goods being produced in China it makes sense that more and more e-commerce platforms are Chinese. The success of Temu and its competitors showcases the power of connecting customers directly with suppliers, ultimately reshaping the way people shop online. TEMU's emergence in the e-commerce landscape with its lightning-fast shipping times has undoubtedly stirred the industry. By setting new standards for efficiency and customer satisfaction, TEMU challenges traditional platforms to step up their game. While the convenience of rapid shipping is undeniable, the long-term sustainability and overall impact of this approach must also be considered. As consumers continue to prioritize convenience and speed, the success of TEMU may very well influence how the e-commerce ecosystem evolves in the years to come. However, to sustain its growth and success, Temu must adapt to evolving customer preferences, optimize its operations, and effectively.

Answer in paragraph format. Only use the context provided for your answer. What factors led to Temu's success? THE RISE OF TEMU: A Shopping App Revolutionizing the Retail Experience Introduction In recent years, the retail industry has witnessed a significant shift towards online shopping. The emergence of E-commerce platforms has transformed the way consumers shop, providing convenience and access to a wide range of products. This case study explores the rise of Temu, a shopping app that has disrupted the traditional retail landscape and revolutionized the shopping experience for millions of users. Temu, a rising star in the world of online shopping, offers a vast array of fashion products, beauty items, and home goods. This Chinese-owned digital marketplace has quickly become the top free shopping app, outshining giants like Shein, Amazon, and Walmart. Temu’s business model connects customers directly to suppliers. By forging strong relationships with retailers, they’ve managed to keep prices low and maintain a vast network of suppliers. At the core of Temu’s rapid growth and competitive pricing is their innovative Next-Gen Manufacturing (NGM) model. Launched in September 2022, this Boston-based e-commerce platform serves markets in the US, Canada, Australia, and New Zealand. The NGM model revolutionizes the retail process by enabling manufacturers to produce merchandise with more precision, reducing unsold inventory and waste. However customers do complain about longer delivery times. It is unknown to what extent this is a result of the NGM model. By connecting shoppers directly with manufacturers and offering real-time insights, Temu is able to cut warehousing and transportation costs, resulting in savings of at least 50% compared to traditional processes. This cost-saving approach allows the company to offer near-wholesale prices, as they remove hidden costs and focus on accurately forecasting sales and demand. While Temu.com is gaining popularity, it faces stiff competition from other Chinese online wholesale stores like AliExpress, DHGate, Banggood, and DealExtreme. These platforms offer a wide range of products at competitive prices, along with diverse shipping options and payment methods. However, Temu stands out with its NGM model, which empowers manufacturers to create customized products. The increased visibility of demand and supply accelerates distribution and eliminates the need for large warehouses. Another distinguishing factor of Temu is its claims on sustainability and social responsibility. The NGM model promotes a more sustainable e-commerce landscape by enabling manufacturers to produce merchandise that fits the needs of consumers, leading to lower unsold inventory and waste. Significance of Temu’s Innovative approach to Shopping In the rapidly evolving world of e-commerce, convenience and speed have become the pillars on which success is built. As consumers increasingly turn to online shopping to meet their needs, the demand for faster shopping times has never been higher. Enter TEMU, the innovative new ecommerce platform that promises to redefine the shopping experience with lightning-fast shipping. TEMU's shopping prowess to traditional e-commerce platforms, makes it stand out and elevates the shopping journey for customers. Speed of Delivery: One of the most glaring advantages TEMU brings to the table is its lightning-fast shipping times. Unlike traditional platforms that often offer standard shipping that can take days or even weeks, TEMU has set a new standard with its express delivery options. With strategically located warehouses and a streamlined logistics network, TEMU ensures that customers receive their orders in record time, sometimes as soon as within a few hours of placing an order. This kind of speed sets TEMU apart from traditional e-commerce platforms, where delays in processing and shipping can often lead to frustration and disappointment for customers. Inventory Management: TEMU's commitment to swift delivery is closely tied to its advanced inventory management system. Traditional platforms often struggle to keep up with the demand, leading to instances where popular items are out of stock or on backorder. TEMU's innovative approach utilizes real-time data analytics to predict customer demands and stock products accordingly. This approach significantly reduces the chances of running out of stock, thus ensuring that customers can find what they want when they want it. Customer Satisfaction: In the world of e-commerce, customer satisfaction is paramount. TEMU's emphasis on fast shipping addresses one of the most common pain points for online shoppers – the waiting game. Traditional platforms often face challenges in providing consistent shipping times, leading to varied customer experiences. TEMU's commitment to speedy delivery contributes to higher levels of customer satisfaction by providing a more reliable and predictable shopping experience. Competitive Edge: As e-commerce continues to grow, the market becomes increasingly saturated with both established giants and new entrants. TEMU's focus on faster shipping times gives it a distinct competitive edge. It appeals to consumers who prioritize efficiency and convenience in their shopping experience. In contrast, traditional platforms may find themselves having to adapt quickly or risk losing customers to the allure of TEMU's swiffer service. Sustainability and Environmental Impact: While speed is a significant selling point for TEMU, it's essential to consider the environmental impact of such rapid shipping. Expedited shipping often requires additional resources, such as expedited transportation and packaging materials. Traditional platforms might adopt more sustainable shipping practices, such as grouping orders or optimizing delivery routes to reduce their carbon footprint. TEMU must balance its commitment to speed with environmental responsibility to ensure a positive long-term impact. Brief Overview of Temu Temu (pronounced ‘tee-moo’) is a Boston-based online marketplace founded by Pinduoduo’s parent company PDD Holding. Its business model is likened to Chinese shopping platforms SHEIN, Wish, and Alibaba – which are based on the sale of large quantities of products at prices that are so low they are almost unbelievable. Temu was founded in the USA in 2022 and is a subsidiary of PDD Holdings Inc., which is listed on Nasdaq and headquartered in Shanghai. Temu operates as an online marketplace similar to AliExpress, Walmart, and Wish, focusing on offering affordable goods. Temu allows Chinese vendors to sell to shoppers and ship directly to them without having to store products in U.S. warehouses.The company acts as an intermediary between sellers (primarily from China) and buyers without maintaining its own inventory. Temu promotes social commerce, encouraging potential buyers to find more buyers to avail discounts. The app employs gamification to engage customers and offers free shipping by circumventing customs duties. The platform allows suppliers based in China to sell and ship directly to customers without having to rely on warehouses in the destination countries . Online purchases on Temu can be made using a web browser or via a dedicated mobile application.Temu offers free products to some users which encourage new people to install the app through affiliate codes, social media and gamification. It also uses online advertising on Facebook and Instagram and many online platforms. The Temu platform went live for the first time in the United States in September 2022 and in February 2023, Temu was launched in Canada. That same month, the company aired a Super Bowl commercial advert . In March 2023, Temu was launched in Australia and New Zealand. The following month, Temu was launched in France , Italy , Germany , the Netherlands , Spain and the United Kingdom. Naturally, the prices charged by the site defy all competition (sneakers for €11, manicure kit for less than €5, phone holder for €1.80, etc.), so much so that the platform has adopted an eloquent slogan: “Buy like a Billionaire”. As the specialist in Chinese digital companies Jeffrey Towson explains to Le Monde, the platform does not yet make a margin, in order to establish itself quickly in the targeted countries. At the end of 2022, the Temu application became the most downloaded application in the United States. The TEMU (Shop Like a Millionaire) Shopping app is now boasting over 100 million Downloads on PlayStore and AppStore with over 4.7 Million reviews and about 12+ Ratings. Three months after its launch in the United States, the application was at the top of downloads. In the European Union, where the platform arrived in April (in France, the United Kingdom, Italy, the Netherlands, Spain and Germany), the success is similar. In recent days, it has been the most downloaded application in France on iOS and Android. As of April 2023, the app has been downloaded 10 million times since its launch in September 2022 and it is currently available in around 100 countries. Temu’s wide range of products is particularly appealing to consumers, combined with a gamified online shopping experience that encourages customers to try their luck and buy more and more. With its impressive growth and distinct strategy, Temu’s business model warrants a closer look. Key Factors that contributed to its initial success Leveraging the power of mobile technology, Temu aimed to bridge the gap between online and offline retail, offering a unique platform that combined the benefits of both worlds. It introduced several innovative features for better customer experience that set it apart from competitors and propelled its rapid rise to popularity. These Key Features and Functionality are; Augmented Reality (AR) Shopping: Temu integrated AR technology into its app, allowing users to virtually try on clothing, visualize furniture in their homes, and experience products before making a purchase. This feature enhanced the shopping experience and reduced the need for physical store visits. Personalized Recommendations: Temu leveraged artificial intelligence and machine learning algorithms to analyze user preferences, browsing history, and purchase behavior. Based on these insights, the app provided personalized product recommendations to users, leading to higher customer satisfaction and increased sales.Certainly! Temu's personalized recommendations were generated through a combination of artificial intelligence (AI) and machine learning algorithms. Here's an overview of how the feature worked: Data Collection: Temu collected vast amounts of user data to understand individual preferences and behavior. This data included user interactions within the app, such as product searches, views, clicks, and purchases, as well as demographic information and user-provided preferences. Data Processing and Analysis: The collected data was processed and analyzed using AI and machine learning algorithms. These algorithms examined patterns, correlations, and relationships within the data to identify user preferences, interests, and buying patterns. User Profiling: Based on the analysis, Temu created user profiles that encompassed various attributes, such as preferred product categories, brands, price ranges, and style preferences. The profiles were continually updated and refined as new data was collected and analyzed. Collaborative Filtering: One common technique used by Temu was collaborative filtering. This approach compares a user's profile with the profiles of other similar users to identify products or items that users with similar preferences enjoyed or purchased. By finding similarities between users, collaborative filtering could suggest relevant products to a particular user based on the preferences of users with similar tastes. Content-Based Filtering: Another technique employed by Temu was content-based filtering. This method focused on the characteristics and attributes of products themselves. It analyzed product descriptions, features, tags, and other metadata to identify similarities and correlations between products. For example, if a user showed a preference for certain brands or specific features, content-based filtering could recommend similar products that match those preferences. Machine Learning and Iterative Refinement: Temu's algorithms continuously learned and improved over time. As users interacted with the app and provided feedback, the algorithms adjusted their recommendations based on the user's responses and behavior. Machine learning techniques enabled the system to adapt and refine its recommendations based on real-time user feedback. Real-Time Contextual Factors: In addition to user preferences, Temu also considered real-time contextual factors, such as trending products, seasonal trends, and popular items in the user's location. These factors were incorporated into the recommendation algorithms to ensure up-to-date and relevant suggestions. By leveraging AI, machine learning, and user data, Temu's personalized recommendation system aimed to understand each user's unique preferences and deliver tailored product suggestions. The algorithms continually evolved to provide increasingly accurate and relevant recommendations, enhancing the user experience and facilitating personalized shopping journeys. Social Commerce Integration: Recognizing the power of social media, Temu incorporated social commerce features, enabling users to share products, create wish lists, and seek recommendations from friends and influencers. This integration expanded Temu's reach and facilitated organic growth through user-generated content. Seamless Checkout and Delivery: Temu prioritized a frictionless shopping experience by streamlining the checkout process and offering multiple secure payment options. Additionally, it partnered with reliable logistics providers to ensure prompt and efficient product delivery, enhancing customer satisfaction and loyalty. Seamless Checkout and Payment Options: Temu focused on streamlining the checkout process to provide a seamless and hassle-free experience for users. It offered multiple secure payment options, including credit/debit cards, mobile wallets, and payment gateways, allowing users to choose their preferred method. This flexibility and ease of payment contributed to a smoother transaction process and reduced cart abandonment rates.Temu implemented several measures to ensure the security of payment options for its users; Secure Payment Gateways: Temu has partnered with trusted and secure payment gateways to handle the processing of user payments. These payment gateways employ robust security measures such as encryption, tokenization, and secure socket layer (SSL) protocols to protect sensitive payment information during transmission. Encryption: Temu has implemented encryption protocols to safeguard user payment data. This involves encrypting sensitive information such as credit card details, bank account numbers, and personal information to prevent unauthorized access or interception. Encryption ensures that even if the data is intercepted, it remains unreadable and unusable to unauthorized parties. Compliance with Payment Card Industry Data Security Standards (PCI DSS): Temu has adhered to the Payment Card Industry Data Security Standards, which are industry-wide standards established to ensure the secure handling of cardholder data. Compliance with PCI DSS involves maintaining a secure network, implementing strong access controls, regularly monitoring and testing systems, and maintaining an information security policy. Two-Factor Authentication (2FA): Temu has implemented two-factor authentication as an additional layer of security for payment transactions. This requires users to provide two forms of verification, such as a password and a unique code sent to their mobile device, to authenticate their identity before completing a payment. Fraud Detection Systems: Temu has employed fraud detection systems and algorithms to identify and prevent fraudulent payment activities. These systems analyze various factors, such as user behavior, transaction patterns, and known fraud indicators, to detect and flag suspicious transactions for further verification or intervention. Regular Security Audits: Temu has conducted regular security audits and assessments to identify vulnerabilities and ensure that all payment systems and processes meet the highest security standards. This includes conducting penetration testing, code reviews, and vulnerability scans to proactively identify and address any potential security weaknesses. User Education and Awareness: Temu has implemented user education programs to raise awareness about safe online payment practices. This could include educating users about the importance of strong passwords, avoiding phishing attempts, and regularly monitoring their payment transactions for any unauthorized activity. Order Tracking and Delivery Updates: Temu provided users with real-time order tracking and delivery updates. Users could monitor the progress of their orders and receive notifications regarding shipment status, estimated delivery time, and any delays. This feature enhanced transparency and kept users informed throughout the delivery process, improving overall customer satisfaction. User Reviews and Ratings: To facilitate informed purchasing decisions, Temu incorporated user reviews and ratings for products. Users could leave feedback and rate their purchases, helping others make well-informed choices. This feature added a layer of trust and credibility to the shopping experience and fostered a community-driven approach to product evaluation. Virtual Stylist and Fashion Advice: Temu introduced a virtual stylist feature that offered personalized fashion advice and styling tips. Users could provide information about their preferences, body type, and occasion, and receive tailored recommendations for outfits and accessories. This feature catered to users seeking fashion inspiration and guidance, enhancing their shopping experience. Temu’s Virtual Stylist feature works in the following ways; It helps Users of the Temu app to create a profile by providing information about their preferences, body type, style preferences, and any specific fashion requirements they may have. The virtual stylist feature uses algorithms and machine learning techniques to analyze the user's profile and understand their style preferences. It considers factors such as color preferences, patterns, clothing types, and previous purchases. The feature assists users in recommendations. Based on the user's profile and preferences, the virtual stylist recommends outfits, clothing items, or accessories that align with their style. These recommendations may include images, descriptions, and links to purchase the recommended items. The feature also provides style tips, fashion trends, and suggestions to help users stay updated and make informed fashion choices. It helps users in Interactive Communication. The virtual stylist often offers Interactive communication channels such as chatbots or messaging systems. Users ask questions, seek styling advice, or provide feedback to further refine the recommendations. The feature helps Integration with User Feedback,it learns and improves over time by incorporating user feedback and preferences. As users interact with the feature, their feedback and engagement help train the algorithm to provide more accurate and personalized recommendations Growth and Adoption over time Temu was ranked No. 12 in the 2022 holiday traffic, topping retailers like Kohl’s and Wayfair. With an average of 41.0 million visitors in November and December, Temu surpassed major ecommerce sites like Kohl’s, Wayfair, and Nordstrom, and was within striking distance of Macy’s. Temu surged ahead of low-price Chinese goods sellers Shein and Wish.com in dramatic fashion. Not only did Temu quickly surpass Wish.com amid its recent downswing, it also managed to leapfrog Shein’s impressive recent gains. Shein’s steady rise has the company now looking to raise capital at a reported $64 billion valuation as reported by Reuters. Wish.com, by comparison, has been hemorrhaging money and has plummeted 98% from its peak stock price, with a market cap below $400 million. Using cheap wares to attract customers can work, but profitability is a challenge when operating under tight margins. High acquisition costs can be a killer, and there will also be a need to pivot into higher-margin goods. Temu is keying on its mobile app for loyalty. Temu’s bargain-basement prices make purchases a low consideration in most cases. Its best use case is when customers realize a need (“Shoot, I left my iPhone charger at the hotel and need another one”) and can buy quickly and cheaply. The app can drive habit formation around this, and the more that shoppers rely on the app the less likely Temu will have to pay for ads to drive conversions. Temu exploded out of the gates and its rapid rise warrants attention. As something of a Wish.com clone, there’s reason to be skeptical it can find long-term profitable growth when its early stage capital eventually rationalizes. Whether Temu avoids a similar fate will come down to whether it can improve upon the Wish.com playbook to build a loyal and engaged user base and drastically reduce customer acquisition costs over time. A killer TikTok strategy and sticky mobile app was key to achieving what its predecessor could not. As originally featured in the Retail Daily newsletter, Amazon has been the most downloaded shopping app in the US for a very long time. It managed to beat local competitors like Walmart, and even international competition from apps like Wish. But with the coming of Temu it looked like Amazon had finally met its match. Going all the way back to 2020, Amazon's shopping app was averaging around 550K downloads per week in the US, according to our estimates. The summer of 2022 was strong, pushing Amazon's downloads to more than double with a range between 800K and 1.2M weekly downloads. And that spike didn't slow down until February, 2023, after which downloads really started sloping down. SHEIN, a clothing retailer that sells "fast fashion" shipped from China, has been chasing Amazon's tail since it launched. Key word being "chasing". SHEIN averaged a little over half of Amazon's downloads back in 2020. They got close a few times but not enough to really take the lead. In January of 2023, that changed and SHEIN's downloads are now about double those of Amazon in the US. SHEIN saw 617K downloads from the App Store + Google Play in the US last week, according to our estimates. And SHEIN isn't even Amazon's biggest threat right now but Temu, a China-based retailer that sells a variety of goods, from clothes to furniture, at very low prices, since its launch late last year. The holiday shopping season was big for Temu. It averaged 2M new downloads every week between November and December, according to our estimates. Downloads dropped since, which makes sense overall, but are still astronomically high in comparison. Temu saw 1.3M new downloads last week in the US. This is a big problem for Amazon which may mean the next Prime Day will be a little more exciting than the last few. And yes, Temu is one of the biggest spends on Apple Search Ads which helps it get those downloads. Challenges Addressed by Temu The traditional retail model is almost getting outdated thereby posing several challenges. While the “customer is always right” mantra has held true for quite some time, the amount of power wielded by consumers has never been higher than it is right now. Customers are no longer forced to choose between just a couple of options when looking to purchase new luxury goods. Not only has the number of retailers expanded exponentially in recent years, but so has the information available to customers. The amount of choice people enjoy today has also led to a waning of brand loyalty, with customers switching between retailers and online/in-store channels from purchase to purchase, depending which best serves their needs at the time. Luxury retailers are not immune to this trend either, as even wealthy customers now tend to shop around for the best option. This decline in brand loyalty customers presents a unique retailing problem, as retailers try to find new and innovative ways to appeal to buyers – both existing and potential; Consumers are Choosing Multichannel Buying Experiences: With more complete e-retail experiences available, and shipping times greatly reduced, it is little wonder around 96% of Americans utilize online shopping in one way or another. However, those same Americans spend about 65% of their total shopping budget in traditional brick-and-mortar locations. In other words, while almost everyone is shopping online, they are making more purchases in stores. Customers are moving seamlessly between online and offline experiences, and are open to retailers who can best facilitate these transitions. Closing the divide between online and offline retail, Temu solves some issues. It is focused on creating a second-to-none customer experience across all channels. Customers are looking for retailers they can trust to deliver exceptional service time and again. They have the right customer which has helped them to create an omnichannel customer experience for consumers to interact wherever and however they wish by incorporating real-time feedback across channels and devices – engaging the customer wherever they may be. Customers Expect a Seamless Experience: When transitioning between online and in-store experiences, customers not only want the same products to be available, they also want their experience to be seamless. This means, if they are a regular online customer, they want to be treated like a regular customer when they visit a brick-andmortar location. This is quite problematic. However, Temu has created this type of fluid online/offline experience for their customers, it has ceased pitting its channels against one another. Centralized customer data has helped it build a seamless, fluid experience beginning with an easily-accessible customer profile. Retailers lacks an outstanding Experience To Attract Customer Loyalty: Customer experience is the biggest contributor towards brand loyalty, the Traditional Retail model makes it difficult to build a good customer experience.Negative experience being the most significant factor in affecting a customer’s likelihood to make a repeat visit. Most customers also serve people in their own working lives, meaning when they are on the other side of the counter, they want to feel important.While promotions and offers can certainly contribute towards helping customers feel like they are special, the real key to an outstanding experience is personalization which the retail model falls short of. Getting to know customers from their previous purchases and interests can help retailers drive loyalty. These insights can be gleaned from data, or even a simple conversation.Temu addresses this challenge by rendering coupons, bonuses and reduced cost to existing and new customers. It is equally personalized with the user. A Siloed Marketing Infrastructure Makes It Expensive and Unwieldy to get Your Message Across; The traditional retail model features separate channels, which makes customer data to become siloed very easily. If all the moving parts of a marketing department are not communicating efficiently and working together, customers become overwhelmed with conflicting or repeated messages. This bombardment of marketing communications has easily had the opposite of the intended effect and driven customers to competitors with a clearer and more congruent message. The right technology and communication procedures can ensure all arms of a marketing team are on the same page. Temu as a modern retailer has been engaging with their customers across many different channels. From SMS, to email and social media, multi-channel communications are essential to engagement which, in turn, drives the creation of the perfect customer experience. So Many Technologies Exist to Drive Marketing and Sales, but They Don’t Seem to Work Together: While the amount of data gathered by businesses keeps growing at an alarming rate, the number of staff available to analyze it is staying more-or-less the same. What’s important, then, is making sure all this data is being used in the correct way and not contributing towards the data silo problem. This means finding a technology solution which can handle the huge amount of data being generated and ensure it is focused in a direction which best benefits rather than overwhelms marketing efforts. The data scientist approach to marketing is only going to become more prevalent as time goes on when creating a truly unified omnichannel service.Temu has ensured that all existing technologies work together which is why they get best results. Only in the combining of streamlined un-siloed data science, seamless cross-channel customer service and marketing, and authentic personalization, can traditional retailers create buyer experiences which can combat the fickle nature of the modern consumer and lead just like Temu. Strategies Implemented to Revolutionize The Retail Industry Temu adopted and implemented some strategies which accounted for its success. Temu’s business model is built around low prices. It offers even more discounts and lower prices than SHEIN, with special offers such as items sold for as little as one cent. Temu further differentiates itself by offering free shipping and returns to customers, which is made possible by PDD Holding’s extensive network of suppliers and shipping partners. An efficient logistics network is not to be underestimated, as problems with supply and distribution networks are seen as a major factor in the failure of Alibaba and Wish to break into the Western market.. Aside this, the following strategies were implemented; Combining Shopping and Entertainment: One-fifth of online shoppers in the U.S. say they miss the in-store shopping experience when they shop online. Temu aimed to bridge this gap and introduced games into the shopping process. By playing games like Fishland, Coin Spin, Card Flip, and others, customers can win rewards that ultimately lead to more time spent on the site and a dopamine rush from winning free items. To keep people playing these games, however, the app relies heavily on referrals, another core business strategy. These games were designed to be simple, addictive, rewarding, and increase user engagement and retention. According to app intelligence firm Sensor Tower, Temu’s average daily sessions per user in the US increased by 23% from October 2022 to January 2023. Some other games in Canada include scratch cards, card games, and cash games. Temu: Shared Shopping Experience: Group Buying is a familiar concept in Asia that Temu has extended to its Western customer base. Essentially, it has increased customers’ bargaining power by forming groups to share a bulk discount. This plays into the aforementioned referral program, which gives discounts to customers who bring new clients to the app and enables a shared shopping experience. Affiliate Programs and Heavy Advertising: As SHEIN had already proven effective, Temu sent free items to a large number of influencers and micro-influencers to promote Temu on YouTube and TikTok. A younger customer base of users under the age of 35 is particularly attractive to Temu, as younger consumers are typically less able and willing to pay large sums for products. Seeing a favorite internet personality or a personal acquaintance promoting the products has led to many young customers to imitate the purchase. Temu’s omnipresence on TikTok and YouTube is seen as a key factor in why this marketplace has taken off so quickly. A strong presence on TikTok and YouTube: Temu has leveraged the power of social media platforms, especially TikTok and YouTube, to spread awareness and generate buzz about its products and offers. The hashtag #temu on TikTok has amassed over 1.3 billion views, while Temu’s official YouTube account videos have grossed over 215 million views since last August. Temu’s marketing strategy relies on creating viral content that showcases its products entertainingly and engagingly, such as unboxing videos, product reviews, challenges, and giveaways. Temu also collaborates with influencers and celebrities with large followings on these platforms. Temu’s Audience: Temu’s primary target audience has been the young and price-conscious generation of online shoppers looking for bargains and discounts. According to a report by Daxue Consulting, the majority of Temu’s followers (32.68%) are aged 25-34, followed by 18-24 (28.57%) and 35-44 (21.43%). Temu appeals to these consumers by offering personalized recommendations based on their preferences and browsing history and gamified features that allow them to earn credits, gifts, and better deals by playing in-app games or inviting their friends to join the app. Referrals: A Win-Win Strategy for Users and Temu Temu has implemented a referral program encouraging users to invite friends and contacts to join the app in exchange for credits and gifts. Users can share their referral links or codes on social media platforms like Facebook, Instagram, and TikTok. For example, users can join a “Fashion Lovers” team and get $20 in credits by inviting five friends who also love fashion within 24 hours. These referrals help users save money on their purchases, help Temu acquire new customers, and expand its network of sellers. Temu’s Marketing and Growth Strategy that led to its Rise Temu's growth has been remarkable in a short period of time. It reached the top downloads in the shopping category of both Apple's App Store and Google Play and is quickly establishing itself as a high-potential and innovative player in the e-commerce industry. Its success is ultimately its low prices, unlocked by their innovative Next-Gen Manufacturing (NGM) model. It employed a multifaceted marketing strategy to drive user acquisition and brand awareness which has been working greatly for them; Influencer Collaborations: To reach a wider audience, Temu has been collaborating with popular social media influencers and celebrities who promoted the app and shared their shopping experiences. Influencers came from a wide range of individuals, including fashion bloggers, lifestyle influencers, beauty gurus, tech enthusiasts, or experts in specific product categories.This strategy generated buzz and created a sense of credibility and trust among potential users. This marketing strategy was successfully implemented through; Influencer Selection: Temu carefully identified and selected influencers who aligned with its target audience, brand values, and product offerings. These influencers typically had a strong online presence, a relevant niche or expertise, and a sizable following. Temu considered factors such as engagement rates, authenticity, and the influencer's ability to create appealing and relatable content. Exclusive Partnerships: Temu forged exclusive partnerships with influencers, often signing them as brand ambassadors or collaborators. These collaborations involved long-term commitments, where influencers actively promoted Temu's app and its features on their social media platforms, websites, or blogs. The exclusivity of these partnerships helped establish a strong association between the influencers and Temu, increasing brand loyalty and credibility. Sponsored Content: Temu engaged influencers to create sponsored content that showcased the app's features, user experience, and the benefits of using Temu for shopping. Influencers shared their personal experiences, demonstrated the app's functionalities, and highlighted the unique advantages of using Temu over other shopping platforms. This content was often shared through blog posts, social media posts, videos, and live streams. Product Reviews and Recommendations: Influencers played a crucial role in reviewing and recommending products available on Temu. They shared their honest opinions and experiences using products from various brands. Their reviews and recommendations helped build trust and credibility among their followers, encouraging them to explore and purchase products through Temu. Giveaways and Contests: Temu collaborated with influencers to host giveaways and contests, where users had the chance to win exclusive prizes or discounts by engaging with the app or participating in specific promotional activities. These initiatives created buzz, generated user excitement, and attracted new users to the platform. Affiliate Marketing: Temu employed affiliate marketing strategies with influencers, where influencers received a commission or referral fee for every user who downloaded the app or made a purchase through their unique referral links. This incentivized influencers to actively promote Temu and its offerings, as their earnings were directly tied to the success of their referrals. Event Participation: Temu partnered with influencers for events such as product launches, fashion shows, or brand campaigns. Influencers attended these events, shared live updates, and provided behind-the-scenes content to their followers, creating a sense of exclusivity and fostering excitement around Temu's activities. User-generated Content: Temu encouraged influencers and their followers to create usergenerated content related to the app. This could include unboxing videos, styling tips, or hauls showcasing products purchased through Temu. Such content served as social proof and encouraged other users to engage with the app and make purchases. Overall, Temu's collaborations with influencers helped amplify its brand message, expand its reach to new audiences, and establish credibility within the social media landscape. By leveraging the influence and creative abilities of influencers, Temu successfully tapped into their followers' trust and engagement, driving user acquisition, and fostering a positive brand image. User Referral Program: Temu has been incentivizing existing users to refer the app to their friends and family by offering discounts or exclusive rewards. This word-of-mouth marketing approach contributed to the app's exponential growth and user acquisition. Targeted Digital Advertising: Temu has been leveraging targeted digital advertising campaigns across various digital platforms like Facebook, Instagram, Twitter, TikTok and soon Telegram focusing on specific demographics and user segments. By tailoring their messaging and creative assets, Temu effectively reached potential users with personalized content. Expansion into New Markets: After gaining traction in its home market, Temu has been expanding its operations into international markets. It strategically entered regions with high smartphone penetration and a growing ecommerce ecosystem. This expansion allowed Temu to tap into a larger customer base and establish itself as a global player in the shopping app industry. Partnerships with Brands and Retailers: Recognizing the importance of strategic alliances, Temu has been forging partnerships with renowned brands and retailers. These collaborations involved exclusive product launches, limitededition collections, and promotional campaigns. By aligning with established names in the retail industry, Temu gained credibility and attracted a wider range of customers. Continuous Innovation: Temu has been prioritizing continuous innovation to stay ahead of the competition. It regularly updated its app with new features and enhancements based on user feedback and emerging trends. For example, it introduced a virtual stylist feature that offered personalized fashion advice and styling tips, further enhancing the user experience. Data-driven Insights: Temu has been leveraging the vast amount of user data it collected to gain valuable insights into consumer behavior, preferences, and trends. These insights were used to refine its product offering, improve targeted advertising efforts, and optimize the overall shopping experience. By harnessing the power of data, Temu was able to make data-informed decisions and stay attuned to evolving customer needs. Seamless Integration with Physical Stores: Recognizing the importance of the omnichannel experience, Temu has been integrating its app with physical stores. It introduced features like in-store barcode scanning, which allowed users to access product information, read reviews, and make purchases directly from their smartphones while inside partner retail locations. This integration blurred the lines between online and offline shopping and provided a seamless and unified experience. Social Impact Initiatives: Temu also has also been focusing on social impact initiatives to connect with socially conscious consumers. It launched sustainable product collections, partnered with NGOs for charitable causes, and implemented eco-friendly packaging practices. These initiatives resonated with environmentally and socially conscious users, further strengthening Temu's brand reputation and loyalty. Continuous Customer Support: Temu has been placing strong emphasis on customer support and responsiveness. It established dedicated customer service channels, including live chat support and a comprehensive FAQ section. Timely and effective customer support enhanced user satisfaction, resolved issues promptly, and fostered a positive brand image. A heavy paid media strategy: Like other well-funded internet companies, Temu appears to be spending heavily for app installs and on search ads. Search for almost any commodity product—especially if your search includes the word “cheap”—and you’re likely to find a Google result for Temu. Temu also gained attention with multiple Super Bowl spots, putting it on the map for many US consumers for the first time. Results and Impacts The rise of Temu as a shopping app has revolutionized the Retail Industry and also Consumer Experience; User Base and Revenue Growth: Within two years of its launch, Temu has amassed millions of active users and experienced exponential revenue growth. Its user-centric approach and innovative features resonated with consumers, driving adoption and usage. Enhanced Customer Experience: Temu's focus on personalization, convenience, and seamless shopping experiences has elevated customer satisfaction levels. Users appreciated the ability to try on products virtually, receive tailored recommendations, and enjoy hassle-free transactions. Disruption of Traditional Retail: The Traditional Retail industry has suffered relatively as a result of the rise of Temu as a Shopping App. It has greatly disrupted traditional brick-and-mortar retail, with many businesses. This is so because with their new innovation, they have explored other parts(online) which the traditional retailers do not have. Its rise has posed several challenges for traditional retailers as they struggle to adapt to the changing landscape; Online Presence and Digital Transformation: Traditional retailers are still struggling with establishing a strong online presence and undergoing digital transformation. Building and maintaining an effective e-commerce website or app requires technical expertise, investment in infrastructure, and a shift in mindset. Adapting to the digital realm is now very challenging for retailers who have primarily operated in brick-and-mortar stores. Competition with E-commerce Giants: E-commerce platforms like Temu with significant resources, a broad customer base, and strong brand recognition which makes it difficult for Traditional retailers to compete with in terms of pricing, product selection, and customer convenience. It can be challenging for them to match the speed, efficiency, and scale of operations offered by online marketplaces. Supply Chain and Logistics: Traditional retailers have gotten used to managing inventory primarily for physical stores and now face challenges in adapting their supply chain and logistics operations to accommodate online sales. Efficient inventory management, order fulfillment, and last-mile delivery is quite complex and requires adjustments to meet the demands of e-commerce customers. Customer Expectations and Experience: Online shoppers have come to expect a seamless and personalized shopping experience. Traditional retailers now struggle to meet these expectations, especially provided they have very limited experience in online customer engagement, personalization, and tailoring recommendations. Adapting to a customer-centric approach and providing a consistent omnichannel experience can be a significant challenge. Data and Analytics: E-commerce platforms like Temu rely heavily on data and analytics to understand customer behavior, preferences, and trends. Traditional retailers have limited experience in collecting, analyzing, and utilizing customer data effectively. Harnessing data to make data-driven decisions and optimize operations is now a significant hurdle for retailers transitioning to an online model. Operational Costs and Margins: Traditional retailers are facing financial challenges to adapt to ecommerce. Online operations require investments in technology, infrastructure, marketing, and fulfillment capabilities. Retailers need to reevaluate their pricing strategies, optimize operational costs, and find ways to maintain profitability in the face of increased competition and potentially lower margins. Brand Differentiation and Customer Loyalty: Building a strong brand and fostering customer loyalty has proven to be more challenging in the online space. Traditional retailers may have developed a loyal customer base through in-person interactions and personalized service. Translating that loyalty to the digital realm and effectively differentiating their brand from competitors needs innovative strategies and marketing efforts which will take time. By leveraging technology and understanding evolving consumer behaviors, Temu has disrupted the retail industry, reshaped shopping habits, and set new standards for convenience and engagement in the digital age; Temu’s Setbacks Despite its rapid rise, its relationship with sister company Pinduoduo has brought about several challenges in delivery of goods as compared to its competitors and other areas; According to reports published in Times, Temu is beginning to develop a reputation for undelivered packages, mysterious charges, incorrect orders and unresponsive customer service. Temu itself acknowledges that its orders take longer to arrive than those from Amazon—typically 7-15 business days as they come from “overseas warehouses.” In a series of Facebook messages with Times, Roper Malloy, a client complained of spending $178 on gifts from Temu for her family, including two drones and some makeup for her daughter which has never arrived. She said she has contacted the company several times for a refund, which has also yet to arrive. On May 17, 2023, Montana Governor Greg Gianforte banned Temu from statewide government devices, as well as ByteDance apps (including TikTok ) , Telegram , and WeChat. In June 2023, the U.S. House Select Committee on U.S.- Chinese Communist Party Strategic Competition stated that Temu did not maintain "even the facade of a meaningful compliance program" with the law. Uyghur on Forced Labor Prevention to keep goods made by forced labor off its platform. In October, the Boston branch of the Better Business Bureau opened up a file on Temu and has received 31 complaints about the website. Temu currently has a C rating on the BBB, and an average customer rating of 1.4 stars out of 5, although from only 20 reviews. (Complaints are separate from reviews, which do not factor into BBB’s official rating.) McGovern at the BBB mentioned that, it’s unusual for such a new company to receive so many complaints in such a short amount of time. Temu has acknowledged and responded to every complaint posted to the BBB website, but many of those complaints remain unresolved. Temu’s sister company, Pinduoduo, has long been accused of hosting sales of counterfeits, illegal goods, or products that do not match their descriptions. (Pinduoduo wrote in its SEC filings that it immediately removes unauthorized products or misleading information on its platform, and freezes the accounts of sellers on the site who violate its policies.) There have been no BBB complaints that allege the goods Temu ships are counterfeit or fake. Additionally, in 2021, the deaths of two Pinduoduo employees spurred investigations and boycotts over the company’s working conditions, according to the New York Times. How Temu could affect the U.S. economy In May 2023, the U.S.-China Economic and Security Review Commission raised concerns about risks to users' personal data on Temu as a shopping app affiliated with Pinduoduo, which was removed from Google Play after some of its versions were found to contain malware. Schmidt, at Vanderbilt, who specializes in security and privacy, is of the opinion that Temu’s data and privacy practices aren’t out of the ordinary; The company collects lots of personal data about users and then deploys that data to sell ads. However, he says that Temu’s rise could have a bigger impact not in terms of privacy concerns, but in terms of pressure on American companies and workers. If more and more American consumers flock to Temu to buy cut-rate goods, that could pressure Amazon and other competitors to slash their prices too which would affect wages. Areas for Improvements Despite its innovative business model and commitment to sustainability, Temu still has some areas that need improvement; Real-Time Shopping: Cost-Effectiveness vs. Plagiarism and Exploitation: Temu’s most innovative and effective strategy has been highly ambivalent and criticized. Similar to SHEIN, Temu has been using a reverse-manufacturing model that relays customer feedback directly to manufacturers. Starting off with smaller quantities that are offered on the marketplace, products in high demand are reordered, while others are replaced. According to Temu, this results in environmental efficiency because product inventory is aligned with customer demand in real time. In addition, a greater number of products can be offered than with traditional retail strategies. With this method, SHEIN was able to launch 150,000 new items in 2020, beating its competitors by a wide margin. Temu Has to Fight Criticism: Critics point to several detrimental effects of this type of 'ultra-fast' commerce: To ensure low prices, manufacturers must keep costs down, contributing to the continued poverty of workers in manufacturing countries. The same goes for product quality and environmental friendliness: Cheap products that break easily contribute to increasing amounts of waste, returned products tend to be dumped rather than recycled or resold, and the high number of new products sold is only possible by ripping off SME fashion designers and creators. TrustPilot reviews reveal a 2.9-star average, with the majority of one-star reviews citing long shipping times, low-quality items, and poor customer service. Low quality items can become a sustainability issue in itself, since those products have a higher chance of ending up in landfill. It’s essential for Temu to address these concerns and maintain a balance between low prices and customer satisfaction. Lessons Learned Temu's rise as a shopping app exemplifies the transformative power of technology in the retail industry. Its success serves as an inspiration for other businesses seeking to adapt and thrive in the digital era. Overall, the rise of Temu as a shopping app has been driven by its commitment to innovation, personalized experiences, strategic partnerships, and a customer-centric approach. The marketplace Temu has achieved impressive success with its business model of offering low-priced products and free shipping, combined with a gamified shopping experience. Temu's strategy also includes group buying, referrals, affiliate programs, and heavy advertising on social media platforms. While Temu's real-time shopping model, which involves relaying customer feedback directly to manufacturers, is seen as innovative and cost-effective, it has also garnered criticism. Critics argue that this approach can lead to environmental issues, exploitation of workers, and plagiarism of designs from small and medium-sized fashion creators. Despite these concerns, Temu's combination of low prices, gamified shopping, and heavy advertising on platforms like TikTok and YouTube has made it a major player in the ultra-fast eCommerce sector. However, Temu's most controversial strategy is its real-time shopping model akin to that of SHEIN, which relays customer feedback directly to manufacturers. While this model increases costeffectiveness and product variety, critics argue that it contributes to environmental degradation, exploitation of workers, and plagiarism of fashion designers. Nonetheless, Temu's growth and distinct strategy make it a noteworthy player in this emerging business model of ultra-fast eCommerce, and it will be interesting to see how this trend plays out in the future. Actionable Takeaways for other Businesses in the Retail Industry Traditional Retailers who wish to also rise like Temu should consider the following steps; Develop a User-Friendly E-commerce Website: Create a well-designed, intuitive, and user-friendly e-commerce website that offers a seamless shopping experience. Ensure that the website is responsive, optimized for mobile devices, and provides easy navigation, product search, and checkout processes. Emphasize Branding and Differentiation: Clearly define the brand identity and unique selling propositions of your retail business. Highlight what sets your products apart from competitors and communicate a compelling brand story to engage online customers. Use high-quality visuals and persuasive copywriting to convey your brand message effectively. Optimize for Search Engines: Implement search engine optimization (SEO) techniques to improve the visibility of your website in search engine results. Conduct keyword research to understand the terms and phrases your target audience is searching for, and optimize your website's content, meta tags, and URLs accordingly. Leverage Social Media: Use social media platforms to build an online community, engage with customers, and promote your products. Regularly post engaging content, including product updates, customer testimonials, and behind-the-scenes glimpses. Encourage user-generated content and respond promptly to customer inquiries and feedback. Invest in Digital Marketing: Develop a comprehensive digital marketing strategy that includes online advertising, email marketing, influencer collaborations, and content marketing. Target specific customer segments and utilize data-driven approaches to reach your audience effectively and drive traffic to your website. Provide Excellent Customer Service: Offer exceptional customer service across all online channels, including live chat, email, and social media. Respond promptly to customer inquiries, provide accurate product information, and address any issues or concerns in a timely manner. Personalize the customer experience as much as possible to build trust and loyalty. Implement Online Customer Engagement Tools: Incorporate tools such as live chat, product reviews, ratings, and personalized recommendations to enhance customer engagement and create a sense of interactivity on your website. Encourage customer feedback and testimonials to build social proof and credibility. Collaborate with Influencers and Online Communities: Partner with relevant influencers or online communities in your industry to extend your reach and tap into their established audiences. Engage in collaborations, product reviews, or sponsorships to increase brand visibility and credibility. Analyze and Optimize: Continuously monitor and analyze website metrics, customer behavior, and online marketing campaigns. Utilize analytics tools to gain insights into what is working and what needs improvement. Optimize your online presence based on data-driven decisions to enhance the user experience and drive conversions. Adapt to Changing Trends: Stay up to date with the latest e-commerce trends, technologies, and consumer preferences. Be willing to experiment, adapt, and embrace new technologies or platforms that can enhance your online presence and provide a competitive edge. By implementing these strategies, traditional retailers can establish a strong online presence, attract online customers, and compete effectively in the digital marketplace. It's important to continuously evaluate and refine your online presence based on customer feedback, market trends, and emerging technologies to stay ahead of the competition. Future Outlook The rise of Temu as a shopping app has been remarkable, and it has successfully disrupted the retail experience by implementing innovative strategies and business models. Looking ahead, there are several key factors that will shape the future outlook of Temu and determine its continued success in the competitive online shopping market; Expansion into New Markets: Temu has already expanded its operations to several countries, including the US, Canada, Australia, New Zealand, France, Italy, Germany, the Netherlands, Spain, and the United Kingdom. To sustain its growth, Temu will likely continue to explore opportunities for expansion into new markets, both within and outside of these regions. This expansion will allow the platform to reach a larger customer base and tap into new consumer preferences and demands. Improvement in Delivery Times: One area of concern for customers is the longer delivery times associated with Temu's Next-Gen Manufacturing (NGM) model. To address this issue, Temu may invest in optimizing its supply chain and logistics processes. By streamlining operations and partnering with efficient shipping providers, Temu can reduce delivery times and enhance the overall customer experience. Enhanced Customer Engagement: Temu's success is partly attributed to its gamification strategies and social commerce approach. To maintain customer engagement and loyalty, Temu will need to continuously innovate and introduce new features that incentivize users to stay active on the platform. This could include personalized recommendations, rewards programs, and interactive shopping experiences. Sustainability and Social Responsibility: Temu has positioned itself as a platform that promotes sustainability and social responsibility through its NGM model, which reduces unsold inventory and waste. Going forward, it will be crucial for Temu to uphold these values and communicate its commitment to sustainability to customers. This can be achieved through transparent supply chain practices, eco-friendly packaging options, and partnerships with ethical suppliers. Competition and Differentiation: While Temu has gained significant traction, it faces strong competition from other Chinese online wholesale platforms and established e-commerce giants. To stay ahead, Temu will need to continue differentiating itself through its NGM model, competitive pricing, and unique product offerings. It should also focus on building a strong brand identity and nurturing customer trust through excellent customer service and reliable purchase protection. navigate the competitive landscape. With its innovative approach and commitment to customer satisfaction, Temu has the potential to continue reshaping the online Conclusion Conclusively, Temu has emerged as a shopping app that is revolutionizing the retail experience through its Next-Gen Manufacturing model and direct-to-supplier approach. By focusing on cost savings, customization, and sustainability, Temu has gained a competitive edge in the market. With a lot of consumer goods being produced in China it makes sense that more and more e-commerce platforms are Chinese. The success of Temu and its competitors showcases the power of connecting customers directly with suppliers, ultimately reshaping the way people shop online. TEMU's emergence in the e-commerce landscape with its lightning-fast shipping times has undoubtedly stirred the industry. By setting new standards for efficiency and customer satisfaction, TEMU challenges traditional platforms to step up their game. While the convenience of rapid shipping is undeniable, the long-term sustainability and overall impact of this approach must also be considered. As consumers continue to prioritize convenience and speed, the success of TEMU may very well influence how the e-commerce ecosystem evolves in the years to come. However, to sustain its growth and success, Temu must adapt to evolving customer preferences, optimize its operations, and effectively.

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Is acupuncture a beneficial treatment for leg pain in patients with sciatica?

1 Effect of acupuncture on leg pain in patients with sciatica due to lumbar disc 2 herniation: A prospective, randomised, controlled trial 3 4 Guang-Xia Shia , Fang-Ting Yua , Guang-Xia Nib , Wen-Jun Wanc , Xiao-Qing Zhoud , 5 Li-Qiong Wanga , Jian-Feng Tua , Shi-Yan Yana , Xiu-Li Menge , Jing-Wen Yanga , 6 Hong-Chun Xiangf , Hai-Yang Fug , Lei Tangc , Beng Zhangd , Xiao-Lan Jie , Guo-Wei 7 Caif*, Cun-Zhi Liua,h** 8 a International Acupuncture and Moxibustion Innovation Institute, School of 9 Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, 10 Beijing, China 11 bSchool of Acupuncture-Moxibustion and Tuina, School of Health and Rehabilitation, 12 Nanjing University of Chinese Medicine, Nanjing, China 13 cDepartment of Rehabilitation, The Central Hospital of Wuhan, Tongji Medical 14 College, Huazhong University of Science and Technology, Wuhan, China 15 dDepartment of Acupuncture and Moxibustion, Shenzhen Hospital, Beijing University 16 of Chinese Medicine, Shenzhen, China 17 ePain Medicine Center, Peking University Third Hospital, Beijing, China 18 fDepartment of Acupuncture, Union Hospital, Tongji Medical College, Huazhong 19 University of Science and Technology, Wuhan, China 20 gDepartment of Acupuncture, Affiliated Hospital of Nanjing University of Chinese 21 Medicine, Nanjing, China 22 hDepartment of Acupuncture, Dongzhimen Hospital Affiliated to Beijing University 23 of Chinese Medicine, Beijing, China 24 Corresponding author* 25 Department of Acupuncture, Union Hospital, Tongji Medical College, Huazhong 26 University of Science and Technology, Wuhan, China. No. 1277 Jiefang Avenue, 27 Jianghan District, Wuhan 430022,China. 28 E-mail Address: [email protected] (G.-W. Cai) 29 Corresponding author** 30 International Acupuncture and Moxibustion Innovation Institute, School of 31 Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No.11 32 Bei San Huan Dong Lu, Chaoyang District, Beijing 100021, China. E-mail 33 Address:[email protected] (C.-Z. Liu) 34 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 35 Summary 36 Background Sciatica is a condition including unilateral leg pain that is more severe 37 than low back pain, and causes severe discomfort and functional limitation. We 38 investigated the effect of acupuncture on leg pain in patients with sciatica due to 39 lumbar disc herniation. 40 Methods In this multi-centre, prospective, randomised trial, we enrolled patients with 41 sciatica due to lumbar disc herniation at 6 hospitals in China. Patients were randomly 42 assigned (1:1:1) to receive either acupuncture at the acupoints on the disease-affected 43 meridian (DAM), or the non-affected meridian (NAM), or the sham acupuncture (SA) 44 3 times weekly for 4 weeks. The primary end point was the change in visual analogue 45 scale (VAS, 0-100) of leg pain intensity from baseline to week 4. This study is 46 registered with Chictr.org.cn, ChiCTR2000030680. 47 Finding Between Jun 9th, 2020, and Sep 27th, 2020, 142 patients were assessed for 48 eligibility, 90 patients (30 patients per group) were enrolled and included in the 49 intention-to-treat analysis. A greater reduction of leg pain intensity was observed in 50 the DAM group than in the other groups: -22.2 mm than the SA group (95%CI, -31.4 51 to -13.0, P <0.001) , and -19.3mm than the NAM group (95% CI, -28.4 to -10.1; P 52 <0.001). However, we did not observe a significant difference in the change of leg 53 pain intensity between the NAM group and the SA group (between-group difference 54 -3.0 [95% CI, -12.0 to 6.1], P=0.520). There were no serious adverse events. 55 Interpretation Compared with SA, acupuncture at the acupoints on the 56 disease-affected meridian, but not the non-affected meridian, significantly reduces the 57 leg pain intensity in patients with sciatica due to lumbar disc herniation. These 58 findings suggest that the meridian-based specificity of acupoint is a considerable 59 factor in the acupuncture treatment. A larger, sufficiently powered trial is needed to 60 accurately assess efficacy. 61 62 Funding The National Key R&D Program of China (No: 2019YFC1712103) and the 63 National Science Fund for Distinguished Young Scholars (No:81825024). 64 Keywords: Acupuncture; leg pain; Acupoint selection; Meridian-based; Sciatica 65 66 67 68 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 69 Research in context 70 Evidence before this study 71 Using the key words "sciatica" and "acupuncture"，we searched PubMed for articles 72 published between Jan 1, 1947 and Jan 5, 2024. Despite an extensive literature search, 73 only a limited number of studies were available. There is ambiguous evidence about 74 the use of acupuncture, with most studies contrasting one another in addition to the 75 lack of high-quality trials. Since the choice of more appropriate acupoints for 76 stimulation is meaningful for acupuncture, studies that investigate the effect of 77 acupuncture on different acupoint program are urgently needed. 78 Added value of this study 79 This multi-centre, assessor and statistician-blinded trial addressed the above 80 limitations by showing that, compared with sham acupuncture, acupuncture at the 81 acupoints on the disease-affected meridian, but not the non-affected meridian, 82 significantly reduces the leg pain intensity in patients with sciatica due to lumbar disc 83 herniation. 84 Implications of all the available evidence 85 We found that acupuncture at the acupoint on the disease-affected meridian had 86 superior and clinically relevant benefits in reducing pain intensity to a greater degree 87 than acupuncture at NAM or SA. The finding is of vital significance to clinical work, 88 as meridian-based specificity of acupoint is one of the most determining factors in the 89 efficacy of acupuncture. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 90 Introduction 91 Sciatica is a common health problem in the general population with a lifetime 92 prevalence of 10% to 43%, depending on different etiologies [1-2]. It is characterised 93 by radiating leg pain starting from the low back, at times accompanied by sensory or 94 motor deficits. In most cases, sciatica is attributable to lumbar disk disorders [3]. The 95 overall prognosis is worse than low back pain, particularly if leg pain extends distal to 96 the knee with signs of nerve root compression, increasing risk for unfavorable 97 outcomes and health care use [4]. Spontaneous recovery occurs in most patients; 98 however, many endure substantial pain and prolonged disability, as 34% reported 99 chronic pain beyond 2 years [5-6]. Optimal pharmacological treatment is unclear due 100 to uncertain benefits or high rates of adverse effects[7-8]. Surgery has been 101 demonstrated to ameliorate sciatica in the early stage, but a proportion of patients do 102 not meet surgical standards or hesitate about the potential complications [9]. The 103 dilemma has led to a soaring increase in complementary and alternative medicine, 104 such as acupuncture [10]. 105 Acupuncture has been recommended for management of low back pain by clinical 106 practice guideline from the American College of Physicians [11-12]. Several studies 107 have also shown that acupuncture was beneficial in treating leg pain, although others 108 have reported discrepancies concerning the efficacy of true vs sham acupuncture[10]. 109 The inconsistent findings may result from variations in study design and insufficient 110 sample size. We conducted this trial to preliminarily evaluate the efficacy and safety 111 of acupuncture in terms of reduction in leg pain with sciatica patients. 112 Acupuncture is garnering increased attention as an effective treatment for pain 113 managemengt, one important issue is whether acupoint choice influences the benefits 114 of acupuncture[10]. However, a well-recognized acupoint program has yet not been 115 established, yielding heterogeneous results across relative studies[13]. Therefore, the 116 second aim of this study was to compare the difference of acupuncture efficacy in 117 patients receiving acupuncture at the acupoints of the disease-affected meridian 118 (DAM), the non-affected meridian (NAM), or sham acupuncture (SA). 119 120 Methods 121 Study design and participants 122 This mult-centre, three-arm, prospective randomised trial was conducted in the 123 inpatient departments of 6 tertiary hospitals in China between Jun 9, 2020 and Sep27, This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 124 2020. The study protocol was approved by the local ethics committee at the 125 coordinating center and each study site (No. 2020BZHYLL0105), and registered with 126 the Chinese Clinical Trial Registry on Chictr.org.cn, ChiCTR2000030680. The 127 protocol has been published previously [14] and is available in open-access full text 128 and in Supplement 1. All patients provided written informed consent before 129 enrolment. 130 Eligible patients were aged 18 to 70 years old , reported leg pain extending below 131 the knee in a nerve root distribution over 4 weeks, had a lumbar disc herniation 132 confirmed by examination signs (positive result on straight leg raise test or sensory or 133 motor deficit in a pattern consistent with a lumbar nerve root) [15], and scored 40 mm 134 or higher on the 100-mm VAS [16]. Imaging (magnetic resonance imaging with or 135 without computed tomography) corroborating a root-level lesion concordant with 136 symptoms and/or signs was determined by the trial clinician. Exclusion criteria were a 137 history or diagnostic result that suggested an inherited neuropathy or neuropathy 138 attributable to other causes, had undergone surgery for lumbar disc herniation within 139 the past 6 months or plan to have spinal surgery or other interventional therapies 140 during next 4 weeks, continually took antiepileptic medication, antidepressant 141 medication, opioids or corticosteroids; had cardiovascular, liver, kidney, or 142 hematopoietic system diseases, mental health disorders, other severe coexisting 143 diseases (e.g., cancer), pregnant, breastfeeding, or women planning conception during 144 the study. Patients participating in other clinical studies within the past 3 months or 145 receiving acupuncture within 6 months were also excluded. The screening process 146 was conducted in the way of in-person visits by trial clinicians. 147 Randomisation and masking 148 The study protocol was explained to all enrolled patients before randomisation. 149 After written informed consent was obtained, patients were allocated randomly (1:1:1) 150 to the three arms: DAM, NAM or SA. Randomisation was performed with a random 151 block size of six. A randomisation sequence was created by a biostatistician who did 152 not participate in the implementation or statistical analysis of trial. The assessor and 153 statistician were blinded to treatment allocation throughout data collection and 154 analysis. 155 Procedures and interventions 156 To exploratively observe whether the effects of acupoint located on two kinds of 157 meridians are different, this trial set two acupuncture groups, in which patients This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 158 received acupuncture at acupoints on the disease-affected meridian (DAM), or the 159 non-affected meridian (NAM), respectively. The bladder (BL) and gallbladder (GB) 160 meridians are directly in the same dermatomes of the sciatic nerve. Since these 161 meridians are consistent with sciatic pain distribution, they are regarded as the 162 disease-affected meridians. 163 Patients assigned to the DAM group received semi-standardized treatment at 164 acupoints on the bladder/gallbladder meridians. Bilateral BL25 and BL26, which 165 localized at the same level as the inferior border of the spinous process of the fourth 166 and the fifth lumbar vertebra (the commonest positions of disc rupture), were needled 167 as obligatory acupoints. For those having symptoms at the posterior side of the leg, 168 BL54, BL36, BL40, BL57, and BL60 were needled as adjunctive acupoints; similarly, 169 GB30, GB31, GB33, GB34, and GB39 were adjunctive acupoints for patients with 170 symptoms at lateral side. For patients who had pain at both posterior and lateral sides, 171 acupuncturists were instructed to select 5 of the 10 adjunctive acupoints. 172 According to the principle of the Traditional Chinese Medicine theory, the liver 173 meridian, the spleen meridian, and the kidney meridian are commonly treated to 174 improve the functional status of the body. These meridians distribute at the inner side, 175 less related to sciatica symptoms, and are regarded as non-affected meridians. For 176 patients in the NAM group, bilateral EX-B7, EX-B4, and unilateral LR9, LR8, LR5, 177 KI7, and SP4 that on the non-affected meridians were selected . 178 Patients assigned to the SA group received acupuncture at 7 non-acupoints which 179 not localized on meridians and with no manipulations. 180 All acupuncture treatments were performed by two senior acupuncturists (length of 181 services ≥5 years), who consistently applied the same standardised protocols. After 182 identifying the location of acupoints, sterile acupuncture needles (length 40 mm, 183 diameter 0.30 mm; Hwato, Suzhou Medical Appliance Factory, China) were inserted, 184 followed by 30s manipulation to acquire Deqi (a sensation of aching, soreness, 185 swelling, heaviness, or numbness). Blunt-tipped placebo needles with similar 186 appearances to conventional needles but no skin penetration were used in the SA 187 group. To maximize the blinding of patients and to fix blunt-tipped placebo needles, 188 adhesive pads were placed on points in all groups. Patients in all groups started 189 treatment on the day of randomization and received twelve 30-minute sessions over 4 190 consecutive weeks at 3 sessions per week (ideally every other day). This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 191 Pain medication was offered if necessary and included paracetamol and optionally 192 non-steroidal anti-inflammatory drugs (Celebrex), short acting opioids, or both. We 193 used questionnaires to monitor the use of pain medication and other co-interventions. 194 Outcomes 195 The primary outcome was the change of leg pain intensity over the preceding 24 196 hours from baseline to week 4 as measured on the VAS. Participants were asked to 197 rate their average leg pain during the last 24 hours out of 100, with 0 representing no 198 leg pain and 100 representing the worst pain imaginable. 199 Secondary outcomes included VAS for leg pain and back pain intensity at other 200 time points. We observed the Oswestry Disability Index (ODI, examining perceived 201 functional disability in 10 activities of daily living), Sciatica Frequency and 202 Bothersomeness Index (SFBI, rating the extent of frequency and bothersomeness of 203 sciatica respectively), 36-item Short Form Health Survey (SF-36, evaluating the 204 quality of life with physical and mental components) . 205 We also assessed levels on the global perceived recovery (assessed by a 7-point 206 Likert self-rating scale with options from “completely recovered” to “worse than 207 ever”) and degrees of the straight leg raise test. 208 The Credibility/Expectancy Questionnaire (CEQ) was used to assess the credibility 209 and expectancy of patients to acupuncture treatment after the first treatment. 210 Moreover, patients were also invited to guess their group for blinding assessment at 211 week 2 and week 4. Adverse events were documented by patients and outcome 212 assessors throughout the trial. All adverse events were categorized as 213 treatment-related or non-treatment-related and followed up until resolution. 214 The researchers in charge of the scale assessment were asked to use the fixed 215 guiding words on the questionnaires to have a conversation with the patient without 216 redundant communication. Due to the trial site and population, we used Chinese 217 versions of the assessment scales that were confirmed to have moderate or higher 218 clinical responsiveness and are suitable for clinical efficacy evaluation. 219 Statistical analysis 220 We designed our trial to determine whether there was a difference between each 221 acupuncture group and the sham acupuncture group in terms of leg pain intensity. 222 According to the method of upper confidence limit, a sample size ranging from 20 to 223 40 could be the guideline for choosing the size of a pilot sample. Considering the 224 overall resource input issues (eg, funding availability and expected completion time), This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 225 the total sample size was preset at 90 patients, 30 patients per group. We performed 226 analyses following the intention-to-treat principle with all randomly assigned patients 227 included. 228 For the primary outcome, analysis of covariance was applied to test the difference 229 between groups in leg pain intensity with baseline values adjusted. Missing data were 230 imputed using multiple imputation method. To address the robustness of the results, 231 we performed a per-protocol analysis for the primary outcome, covering patients who 232 complete 10 sessions or more and had no major protocol violations (e.g., using 233 additional treatments during the treatment period). One-way ANOVA was performed 234 for the secondary outcomes including leg pain at each measuring time point, back 235 pain, ODI, SFBI, SF-36, CEQ, PDQ, global perceived recovery scores, and degrees of 236 straight leg raise test. The blinding assessment, the proportion of patients using 237 additional treatments and adverse event rates were analyzed using the χ2 test or Fisher 238 exact test. Between-group differences were tested through the least significance 239 difference (LSD)-t test. Categorical variables are presented as n (%) and continuous 240 variables are presented as the mean (SD) or median (interquartile range, IQR) . All 241 tests applied were two-tailed, p < 0.05 was considered statistically significant. An 242 independent statistician completed the analyses using IBM SPSS Statistics version 20 243 (IBM Corp, Armonk, NY). 244 Role of the funding source 245 The funder of the study had no role in the study design, data collection, data 246 analysis, or writing of the report. All authors had full access to the data in the study 247 and gave the final approval of the manuscript and agree to be accountable for all 248 aspects of work. 249 Results 250 Patient characteristics 251 Between Jun 9th, 2020, and Sep 27th, 2020, 142 patients were assessed for 252 eligibility, 90 patients (30 patients per group) were enrolled and included in the 253 intention-to-treat analysis (Figure 1). Mean age of patients was 44.2 (SD 14.9) years, 254 and 51 (56.7%) were female. Mean symptom duration was 2.0 years (IQR 0.7 to 4.1) 255 with a mean VAS score of 62.3 (SD 14.3) mm for their leg pain intensity. Overall, 75 256 (83.3%) patients completed the assigned 12 sessions of study interventions, and 82 257 (91.1%) received at least 10 sessions. The primary outcome visit was attended by 82 258 patients at week 4, corresponding to a follow-up rate of 91.1%, which was maintained This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 259 to week 26. There was no difference among groups regarding the usual risk factors for 260 sciatica, such as gender, age, body-mass index, or Disk herniation level, which 261 confirmed that the groups were well matched. The baseline characteristics of patients 262 are summarized in Table 1. 263 After receiving 4-week treatment, the change of leg pain intensity decreased by 264 -36.6 mm (95% CI, -43.1 to -30.2) in the DAM group, by -17.4 mm in the NAM 265 group and by -14.4 mm (95% CI, -20.9 to -8.0) in the SA group. Changes in the leg 266 pain intensity over 4-week period differed significantly among the 3 groups. A greater 267 reduction was observed in the DAM group than in the other groups: -22.2 mm 268 reduction in leg pain intensity than in the SA group (95% CI, -31.4 to -13.0, P＜ 269 0.001) , and -19.3 mm reduction in leg pain intensity than in the NAM group (95% CI, 270 -28.4 to -10.1; P <0.001). While no significant change in leg pain intensity was 271 observed between the NAM and SA groups (mean difference, -3.0 mm, 95% CI, -12.0 272 to 6.1, P=0.52) (Figure 2). 273 We observed that outcomes at the 26-week follow-up were similar in direction to 274 the those at the end of an 4-week period. At week 26, a difference in the change of leg 275 pain intensity were present between the DAM and SA groups (mean difference, -13.3 276 mm, 95% CI, -23.2 to -2.8, P=0.01), between the DAM and NAM groups (mean 277 difference, -13.4 mm, 95%CI, -23.6 to -3.1, P=0.011), but not between the NAM and 278 SA groups (mean difference, 0.1 mm, 95% CI, -10.3 to 10.5, P=0.99) (Figure 2). 279 Sensitive analyses did not alter the result in the primary analysis (eTable 1 and eTable 280 2 in Supplement 2). 281 We found a greater reduction in back pain intensity over SA for patients who 282 received DAM at week 4 (mean difference, -18.0 mm, 95% CI, -27.7 to -8.4, P＜ 283 0.001). The difference in back pain changes was not significant between the NAM 284 and SA groups at week 4 (mean difference, -4.2 mm, 95% CI, -13.6 to 5.3, P=0.38). 285 At week 26, no difference was detected in back pain relief across the 3 groups. 286 We also found a greater decrease in disability scores in the DAM group over SA at 287 week 4 (mean difference, -10.7 points, 95% CI, -18.3 to -3.1, P=0.007), while there 288 was no difference between the NAM and SA groups (mean difference, -3.1 points, 289 95%CI, -10.6 to 4.3, P=0.41). Similar results were observed at week 26, which 290 favored acupuncture at DAM (mean difference between DAM and SA, -11.1 points, This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 291 95%CI, -19.4 to -2.8, P=0.01) rather than acupuncture at the NAM (mean difference 292 between NAM and SA, -2.7 points, 95%CI, -11.0 to -5.7, P=0.53). 293 Compared to SA, patients in the DAM group reported better symptom 294 improvement on the global perceived recovery test, and lower scores in both 295 frequency and bothersomeness scales on the SFBI. Nonetheless, the measurement of 296 the quality of life, or the degree of the straight leg raise test did not show a difference 297 across the 3 groups (Table 2). Five (16.7%) patients in the DAM group and 4 (13.3%) 298 patients in the SA group take rescue medicine for a short period (eTable 3 in 299 Supplement 2). For blinding assessment, we found no difference across groups in the 300 proportion of patients who correctly guessed the kind of intervention they had 301 received at week 2 and week 4 (eTable 4 in Supplement 2). Outcomes measured at 302 other time points were shown in eTable 5 and e Figure in Supplement 2. 303 Adverse events 304 Three (10%) patients in the NAM group reported post-needling pain which 305 decreased in the following week spontaneously. Adverse events unrelated to the study 306 interventions including increased leg pain, dizziness, insomnia, etc, were all rated as 307 mild to moderate (eTable 6 in Supplement 2). No serious adverse event occurred 308 during the study period. 309 Interpretation 310 To our knowledge, our study is a multi-center clinical trial to show the beneficial 311 effect of acupuncture for patients with moderate-to-severe sciatica of varying duration 312 and is the first to explore the meridian-based acupoint program in this field. We found 313 that acupuncture at the DAM had superior and clinically relevant benefits in reducing 314 leg pain intensity to a greater degree than acupuncture at NAM or SA. Improvements 315 in functional disability, back pain, frequency and bothersomeness and global 316 perceived recovery were also found. Moreover, no significant differences was 317 observed with respect to any outcome between NAM and SA groups. 318 The findings of the current study demonstrate that acupuncture at the acupoints on 319 the disease-affected meridian was clinically beneficial and superior to SA for leg pain. 320 We acknowledge the commonly recognised minimally clinically important difference 321 (MCID) is 10-20 of 100 for pain intensity [16]. The clinically important mean leg 322 pain reduction at the 4-week of treatment in DAM group was -22.2 mm, and 323 continued the trend of a mean clinical important result at 26-week follow-up (-13.3 324 mm). Before our study, Liu and colleagues evaluated the effect of acupuncture in This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 325 relieving leg pain for patients with chronic discogenic sciatica compared with sham 326 acupuncture [13]. Acupuncture showed a small but not clinically relevant effect, with 327 a between-group difference in the 4-week on mean VAS score for leg pain was 7.28， 328 which is not reach the MCID. More acupoints on the disease-affected meridian were 329 adapted in our trial (7 v 4 acupoints on the bladder and/or the gallbladder meridian) 330 which may interpret the discrepancy. 331 Our findings are consistent with a meta-analysis showing that acupuncture was 332 more effective than conventional medicine in managing the pain associated with 333 sciatica, with a significantly greater reduction in pain intensity by 12.5 (95% CI: 334 −16.3 to −8.6) [17]. It is worth noting that the most commonly used acupoints were 335 Huantiao (GB 32), Weizhong (BL 40), and Yanglingquan (GB 34), all on the bladder 336 and/or gallbladder meridians that were directly related with dermatomal distributions 337 of sciatic nerve. Acupuncture at the DAM was more effective than at the NAM in 338 alleviating pain severity during the 4-week treatment and the follow-up period. The 339 acupoints in NAM group are mainly located on the Liver, Spleen and Kidney 340 meridian, which are not affected directly by sciatica in Traditional Chinese Medicine. 341 We speculate that the varied efficacy between the DAM and NAM relate to 342 meridian-based acupoint specificity. 343 Acupuncture at the DAM showed significant superiority in the primary outcome 344 and in most of the second outcomes at the end of therapy. However, no significant 345 differences were observed in the quality of life or the degree of the straight leg raise 346 test among the three groups. The health status and body function are more likely be 347 affected by physical factors and psychological factors [18-19]. In addition, pain may 348 limit function, so as pain decreases, function (straight leg raise) may increase until 349 pain again limits functional capacity. This may explain the improvement in pain 350 without measurable proved function [20]. 351 In Dr. Vickers’ and his groups 2018 update of the meta-analysis of acupuncture for 352 chronic pain study, the authors did not finding any statistically significant influence 353 from point selection on treatment outcome by acupuncture [11]. Another two clinical 354 trials on acupuncture for low back pain, where the first showed no difference between 355 two different acupuncture recipes [21] and the subsequent detected no difference 356 between and real and sham acupuncture (where the sham treatment involved different 357 bodily locations) [22]. The efficacy of acupuncture is related to the dose, point This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 358 selection and treatment time (duration and frequency), and we could not isolate which 359 components contributed to the benefits. Our study only partially answer that acupoint 360 choice could influence the efficacy of acupuncture. 361 Practice guidelines recommend an initial period of conservative care focused on 362 non-pharmacologic treatments for persons with recent-onset sciatica, except in rare 363 instances of rapidly progressing or severe neurologic deficits that may require 364 immediate surgical intervention. In this study, acupuncture hastened pain and 365 functional improvement, indicating that acupuncture could be offered to patients with 366 sciatica lasting at least 4 weeks (mean duration of 2.0 years) as promising 367 non-pharmacologic care. However, prior studies enrolled patients with more acute 368 conditions who may have been more prone to spontaneous recovery than our 369 participants, which limit the generalizability of the trial findings. 370 Acupuncture has regionally specific effect or segmental effect [23-24]. Acupoints 371 located directly on injured nerves could inhibit the nociceptive pathway at the same 372 spinal level and give an analgesic effect at the same dermatomal level [25]. However, 373 the underlying mechanism is not fully elucidated and is worthy of further study. 374 This study had several strengths. Rigorous methods have been used to test the 375 preliminary efficacy of acupuncture in this pilot study. The use of blunt-tipped 376 placebo needles ensured the implementation of blinding, which can make the patients 377 have the feeling of acupuncture under the premise that the needle tip does not 378 penetrate the skin. The high recruitment rate has reflected the willingness to 379 participate among patients with sciatica. The compliance rate (83.3%) and follow-up 380 rate (91.1%) for this pilot trial are satisfactory. Therefore, the current study may 381 provide a more accurate basis for assessing the sample size and selection of 382 acupuncture acupoints for the large-scale trial to be conducted. 383 Limitations 384 Some limitations have to be acknowledged. First, we run this multi-center trial in 385 order to text the feasiblity to implement a large-scale RCT to further confirm the 386 efficacy of acupuncture in this regard. However, with only 90 participants spread over 387 six centers, the effect from the numerous treatment centers should be probably 388 accounted. Second, due to the nature of acupuncture, it was not possible to blind 389 acupuncturists to treatment assignment. But they were trained in advance to follow a 390 standard operating procedure and keep equal communication with patients. Third, 391 although sensitive analysis indicated similar conclusions, the robustness of our This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 392 finding was decreased by the small sample size with a wide credible interval 393 generated, thus further studies with sufficient sample size are needed. Fourth, a 394 treatment that offered 3 sessions per week for continuous 4 weeks was proposed to be 395 burdensome for part of the patients, especially for those who are employed. Treatment 396 with a gradually decreased frequency should be applied in future studies. 397 Conclusion 398 Acupuncture was safely administered in patients with mild to moderate sciatica 399 caused by lumbar disc herniation. To accurately assess the efficacy, a larger, 400 sufficiently powered trial is needed. Acupuncture at the acupoint on the 401 disease-affected meridian had superior and clinically relevant benefits in reducing 402 pain intensity to a greater degree than acupuncture at NAM or SA. Data supported the 403 meridian-based specificity of acupoint is one of the most determining factors in the 404 efficacy of acupuncture. 405 406 References 407 1. Gadjradj PS, Rubinstein SM, Peul WC, et al. Full endoscopic versus open 408 discectomy for sciatica: randomised controlled non-inferiority trial. BMJ. 2022; 409 376:e065846. 410 2. Konstantinou K, Dunn KM. Sciatica: review of epidemiological studies and 411 prevalence estimates. Spine. 2008; 33:2464-2472. 412 3. Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ. 413 2007; 334:1313-1317. 414 4. Deyo RA, Mirza SK. Herniated Lumbar Intervertebral Disk. N Engl J Med. 2016; 415 374:1763-1772. 416 5. Ropper AH, Zafonte RD. Sciatica. N Engl J Med. 2015; 372:1240-1248. 417 6. Mehling WE, Gopisetty V, Bartmess E, et al. The prognosis of acute low back 418 pain in primary care in the United States: a 2-year prospective cohort study. Spine. 419 2012; 37:678-684. 420 7. Jensen RK, Kongsted A, Kjaer P, Koes B. Diagnosis and treatment of sciatica. 421 BMJ. 2019; 367:l6273. 422 8. Kreiner DS, Hwang SW, Easa JE, et al. An evidence-based clinical guideline for 423 the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J. 424 2014 ;14(1):180-191. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 425 9. Manchikanti L, Knezevic E, Latchaw RE, et al. Comparative Systematic Review 426 and Meta-Analysis of Cochrane Review of Epidural Injections for Lumbar 427 Radiculopathy or Sciatica. Pain physician. 2022; 25:E889-e916. 428 10. Ji M, Wang X, Chen M, et al. The Efficacy of Acupuncture for the Treatment of 429 Sciatica: A Systematic Review and Meta-Analysis. Evid Based Complement 430 Alternat Med. 2015;2015:192808. 431 11. Vickers AJ, Vertosick EA, Lewith G, et al. Acupuncture for Chronic Pain: 432 Update of an Individual Patient Data Meta-Analysis. J Pain. 2018;19(5):455-474. 433 12. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive Treatments for Acute, 434 Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the 435 American College of Physicians. Ann Intern Med. 2017;166(7):514-530. 436 13. Huang Z, Liu S, Zhou J, Yao Q, Liu Z. Efficacy and Safety of Acupuncture for 437 Chronic Discogenic Sciatica, a Randomized Controlled Sham Acupuncture Trial. 438 Pain Med. 2019;20(11): 2303-2310. 439 14. Yu FT, Ni GX, Cai GW, et al. Efficacy of acupuncture for sciatica: study 440 protocol for a randomized controlled pilot trial. Trials. 2021;22:34. 441 15. Jensen RK, Kongsted A, Kjaer P, Koes B. Diagnosis and treatment of sciatica. 442 BMJ 2019;367:l6273. 443 16. Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: 444 what is moderate pain in millimetres? Pain. 1997;72:95-7. 445 17. Schroeder K, Richards S. Non-specific low back pain. Lancet 2012;379:482-91 446 18. Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of context 447 effects on health outcomes: A systematic review. Lancet 448 2001;357(9258):757-762 449 19. Ropper AH, Zafonte RD. Sciatica. New Engl J Med 2015;372(13):1225–1240. 450 20. Cherkin DC, Sherman KJ, Avins AL, Erro JH, Ichikawa L, Barlow WE, Delaney 451 K, Hawkes R, Hamilton L, Pressman A, Khalsa PS, Deyo RA. A randomized trial 452 comparing acupuncture, simulated acupuncture, and usual care for chronic low 453 back pain. Arch Intern Med. 2009;169(9):858-866. 454 21. Donna Kalauokalani, Daniel C Cherkin, Karen J Sherman. A comparison of 455 physician and nonphysician acupuncture treatment for chronic low back pain. 456 Clin J Pain. 2005;21(5):406-411. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 457 22. Goldberg H, Firtch W, Tyburski M, et al. Oral steroids for acute radiculopathy 458 due to a herniated lumbar disk: a randomized clinical trial. JAMA. 459 2015;313:1915-1923. 460 23. Zhang R, Lao L, Ren K, Berman B. Mechanisms of 461 acupuncture-electroacupuncture on persistent pain. Anesthesiology. 462 2014;120(2):482-503. 463 24. Cheng K. Neuroanatomical basis of acupuncture treatment for some common 464 illnesses. Acupunct Med. 2009;27(2):61-4. 465 25. Cheng KJ. Neuroanatomical basis of acupuncture treatment for some common 466 illnesses. Acupuncture in medicine: journal of the British Medical Acupuncture 467 Society. 2009;27:61-64. 468 469 Figure legends 470 Figure 1. Modified CONSORT flow diagram. 471 Figure 2. VAS scores for leg pain intensity. 472 Tables 473 Table 1. Baseline characteristics of participants. 474 Table 2. Primary and secondary outcomes measured at week 4 and week 26. 475 476 Contributors 477 CZL is the guarantor for the article. CZL, GXS and FTY designed the trial. GWC, 478 GXN, WJW, XQZ, and XLM offered administrative support. FTY, HCX, HYF, LT, 479 BZ, and XLJ recruited and followed up patients. LQW, JFT and JWY were 480 responsible for study monitoring. SYY and JWY take responsibility for the accuracy 481 of the data analysis. All authors had full access to the data in the study and gave the 482 final approval of the manuscript and agree to be accountable for all aspects of work. 483 484 Data sharing statement 485 Data are available from the corresponding author on reasonable request. 486 Declaration of interests 487 The authors declare no conflict of interest. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed Figure 1. Modified CONSORT flow diagram. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed Figure 2. VAS scores for leg pain intensity. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 1 Table 1. Baseline characteristics of participants. Characteristic DAM group (n=30) NAM group (n=30) SA group (n=30) Age, year, mean (SD) 41.6 (14.7) 44.8 (15.0) 46.1 (15.1) Sex, no. (%) Female 21 (70.0) 16 (53.3) 14 (46.7) Male 9 (30.0) 14 (46.7) 16 (53.3) Marital status, no. (%) Married 22 (73.3) 23 (76.7) 24 (80.0) Single 8 (26.7) 7 (23.3) 6 (20.0) Occupation, no. (%) Mental work 24 (80.0) 24 (80.0) 20 (66.7) Manual work 6 (20.0) 6 (20.0) 10 (33.3) BMI, kg/m2, mean (SD) 22.6 (3.1) 23.3 (2.5) 23.0 (2.7) Duration of sciatica, year, median (IQR) 1.7 (0.4, 5.0) 1.8 (0.7, 3.3) 2.1 (0.7, 6.3) History of acupuncture, no. (%) Yes 13 (43.3) 15 (50.0) 9 (30.0) No 17 (56.7) 15 (50.0) 21 (70.0) Positive straight leg raise test, no. (%) 12 (40.0) 19 (63.3) 16 (53.3) Numbness, no. (%) 20 (66.7) 17 (56.7) 23 (76.7) Tingling, no. (%) 17 (56.7) 21 (70.0) 17 (56.7) Sensory deficit, no. (%) 4 (13.3) 3 (10.0) 3 (10.0) Muscle weakness, no. (%) 8 (26.7) 8 (26.7) 8 (26.7) This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 2 Reflex changes, no. (%) 1 (3.3) 1 (3.3) 1 (3.3) Disk herniation level, no. (%) L3-L4 2 (6.7) 0 (0.0) 0 (0.0) L4-L5 6 (20.0) 14 (46.7) 7 (23.3) L5-S1 9 (30.0) 4 (13.3) 8 (26.7) More than one level 13 (43.3) 12 (40.0) 15 (50.0) Leg pain intensity*, mm, mean (SD) 59.5 (12.3) 63.2 (14.8) 64.3 (15.7) Back pain intensity*, mm, mean (SD) 58.9 (25.2) 56.2 (23.6) 54.6 (26.0) ODI score†, mean (SD) 38.3 (13.0) 38.0 (15.7) 38.2 (14.8) SFBI score‡, mean (SD) Frequency 13.7 (4.4) 14.5 (4.5) 13.7 (5.2) Bothersomeness 12.3 (3.6) 12.5 (3.9) 12.9 (5.0) SF-36 score§, mean (SD) Physical Component 28.5 (10.4) 33.5 (11.5) 31.0 (10.3) Mental Component 52.4 (12.1) 47.6 (15.3) 49.9 (13.1) PDQ score¶, mean (SD) 10.5 (5.5) 12.3 (5.4) 10.7 (6.3) Credibility score**, mean (SD) 0.3 (2.5) 0 (2.6) -0.3 (2.8) Expectancy score**, mean (SD) 0.5 (2.6) -0.4 (3.0) -0.1 (2.7) * Scores range from 0 to 100, with higher scores indicating more severe pain. † Scores range from 0 to 100, with higher scores indicating worse disability. ‡ Scores range from 0 to 24, with higher scores indicating more severe symptoms. § Scores are based on normative data and have a mean (±SD) of 50±10, with higher scores indicating a better This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 3 quality of life. ¶ Scores range from 0 to 30, with higher scores indicating more neuropathic pain. ** Scale has Mean = 0.0 (SD = 1.0) since the items were converted to z-scores before averaging. DAM, the disease-affected meridian; NAM, the non-affected meridian; SA, Sham acupuncture. SD, standard deviation; IQR, interquartile range; BMI, body mass index; ODI, Oswestry Disability Index; SFBI, Sciatica Frequency and Bothersomeness Index; SF-36, 36-item Short Form Health Survey; PDQ, PainDETECT questionnaire. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 4 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 1 Table 2. Primary and secondary outcomes at week 4 and week 26 DAM vs SA NAM vs SA DAM vs NAM Outcome DAM group NAM group SA group P value Difference P value Difference P value Difference P value Primary outcome Change of leg pain intensity at week 4* -36.6 (-43.1, -30.2) -17.4 (-23.8, -11.0) -14.4 (-20.9, -8.0) ＜0.001 -22.2 (-31.4, -13.0) ＜0.001 -3.0 (-12.0, 6.1) 0.520 -19.3 (-28.4, -10.1) ＜0.001 Secondary outcomes Change of leg pain intensity at week 26‡ -35.5 (-42.8, –28.3) -22.2 (-29.3, -15.0) -22.2 (-29.7, -14.7) 0.016 -13.3 (-23.2, -2.8) 0.014 0.1 (-10.3, -10.5) 0.989 -13.4 (-23.6, -3.1) 0.011 Change of back pain intensity Week 4† -34.9 (-41.7, -28.2) -21.1 (-27.6, -14.6) -16.9 (-23.8, -10.0) 0.001 -18.0 (-27.7, -8.4) ＜0.001 -4.2 (-13.6, 5.3) 0.380 -13.8 (-23.2, -4.5) 0.004 Week 26‡ -33.5 (-41.6, -25.4) -23.6 (-31.8, -15.5) -22.7 (-31.1, -14.2) 0.128 -10.8 (-22.6, 0.9) 0.07 -1.0 (-12.7, 10.8) 0.871 -9.9 (-21.4, -1.6) 0.092 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 2 ODI score Week 4† 18.0 (13.9, 22.1) 25.5 (19.6, 31.5) 28.7 (22.6, 34.7) 0.019 -10.7 (-18.3, -3.1) 0.007 -3.1 (-10.6, 4.3) 0.406 -7.5 (-14.9, -0.1) 0.046 Week 26‡ 14.9 (10.0, 19.8) 23.3 (17.1, 29.5) 26.0 (19.1, 32.8) 0.025 -11.1 (-19.4, -2.8) 0.010 -2.7 (-11.0, 5.7) 0.527 -8.4 (-16.6, -0.3) 0.043 SFBI frequency score Week 4† 6.6 (4.9, 8.4) 10.6 (8.7, 12.5) 10.8 (8.5, 13.1) 0.005 -4.1 (-6.9, -1.4) 0.004 -0.2 (-2.9, 2.5) 0.874 -3.9 (-6.6, -1.2) 0.005 Week 26‡ 5.8 (3.7, 7.8) 10.1 (7.8, 12.5) 10.0 (7.4, 12.5) 0.010 -4.2 (-7.4, -1.0) 0.011 0.2 (-3.1, 3.4) 0.928 -4.4 (-7.5, -1.2) 0.007 SFBI bothersomeness score Week 4† 5.6 (4.0, 7.1) 8.9 (7.2, 10.6) 10.2 (8.1, 12.2) 0.001 -4.6 (-7.1, -2.1) ＜0.001 -1.3 (-3.7, 1.2) 0.306 -3.3 (-5.8, -0.9) 0.007 Week 26‡ 4.9 (3.2, 6.6) 8.5 (6.5, 10.5) 9.0 (6.6, 11.4) 0.007 -4.1 (-6.9, -1.3) 0.004 -0.5 (-3.3, 2.3) 0.742 -3.7 (-6.4, -0.9) 0.009 SF-36 physical component score Week 4† 37.3 (32.8, 41.7) 37.7 (33.7, 41.6) 33.8 (28.9, 38.7) 0.390 3.5 (-2.7, 9.6) 0.268 3.9 (-2.2, 9.9) 0.206 -0.4 (-6.4, 5.6) 0.888 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 3 Week 26§ 44.7 (39.9, 49.4) 40.1 (35.3, 44.8) 37.4 (32.0, 42.8) 0.104 7.3 (0.4, 14.2) 0.038 2.7 (-4.2, 9.5) 0.443 4.6 (-2.0, 11.3) 0.166 SF-36 mental component score Week 4† 53.7 (49.7, 57.6) 48.6 (43.2, 54.0) 51.9 (47.2, 56.7) 0.287 1.8 (-4.9, 8.4) 0.600 -3.3 (-9.9, 3.2) 0.314 5.1 (-1.4, 11.6) 0.122 Week 26§ 55.1 (51.7, 58.4) 51.2 (46.0, 56.4) 53.3 (48.6, 58.1) 0.438 1.7 (-4.5, 8.0) 0.580 -2.1 (-8.4, 4.1) 0.496 3.9 (-2.1, 9.8) 0.201 Degree of straight leg raise test Week 4¶ 70.1 (63.8, 76.5) 67.2 (61.0, 73.4) 68.5 (61.6, 75.3) 0.797 1.7 (-7.3, 10.6) 0.708 -1.3 (-10.1, 7.6) 0.774 3.0 (-5.8, 11.7) 0.502 Week 26** 74.9 (70.7, 79.1) 70.3 (62.7, 77.9) 69.8 (64.1, 75.4) 0.402 5.1 (-3.2, 13.4) 0.222 0.5 (-7.7, 8.7) 0.902 4.6 (-3.6, 12.8) 0.267 PDQ score Week 4† 6.7 (4.4, 9.2) 9.3 (7.8, 10.8) 8.0 (5.8, 10.2) 0.193 -2.5 (-5.3, 0.2) 0.071 1.3 (-1.5, 4.1) 0.351 -1.2 (-4.1, 1.6) 0.392 Week 26‡ 4.9 (3.3, 6.4) 9.0 (7.7, 10.4) 8.1 (6.0, 10.1) 0.001 -4.1 (-6.4, -1.9) ＜0.001 1.0 (-1.3, 3.3) 0.408 -3.2 (-5.5, -0.9) 0.007 Global perceived This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 4 recovery Week 4† 1.5 (1.2, 1.9) 2.6 (2.1, 3.1) 2.9 (2.4, 3.5) ＜0.001 -1.4 (-2.1, -0.7) ＜0.001 -0.3 (-1.0, 0.3) 0.301 -1.1 (-1.7, -0.4) 0.001 Week 26‡ 1.8 (1.4, 2.2) 2.6 (2.1, 3.0) 2.8 (2.3, 3.3) 0.005 -1.0 (-1.7, -0.4) 0.002 -0.2 (-0.9, 0.4) 0.460 -0.8 (-1.4, -0.2) 0.014 Estimates are expressed as mean (95%CI). * Data imputed through the last observation carried forward approach. † The number of participants providing data was 27 in the DAM group, 29 in the NAM group and 26 in the SA group at week 4. ‡ The number of participants providing data was 28 in the DAM group, 28 in the NAM group and 26 in the SA group at week 26. §The number of participants providing data was 28 in the DAM group, 28 in the NAM group and 24 in the SA group at week 26. ¶ The number of participants providing data was 27 in the DAM group, 28 in the NAM group and 26 in the SA group at week 4. ** The number of participants providing data was 25 in the DAM group, 26 in the NAM group and 25 in the SA group at week 26. DAM, the disease-affected meridian; NAM, the non-affected meridian; SA, Sham acupuncture. ODI, Oswestry Disability Index; SFBI, Sciatica Frequency and Bothersomeness Index; SF-36, 36-item Short Form Health Survey; PDQ, PainDETECT questionnaire. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 5 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed

Only provide commentary from the context included. Is acupuncture a beneficial treatment for leg pain in patients with sciatica? 1 Effect of acupuncture on leg pain in patients with sciatica due to lumbar disc 2 herniation: A prospective, randomised, controlled trial 3 4 Guang-Xia Shia , Fang-Ting Yua , Guang-Xia Nib , Wen-Jun Wanc , Xiao-Qing Zhoud , 5 Li-Qiong Wanga , Jian-Feng Tua , Shi-Yan Yana , Xiu-Li Menge , Jing-Wen Yanga , 6 Hong-Chun Xiangf , Hai-Yang Fug , Lei Tangc , Beng Zhangd , Xiao-Lan Jie , Guo-Wei 7 Caif*, Cun-Zhi Liua,h** 8 a International Acupuncture and Moxibustion Innovation Institute, School of 9 Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, 10 Beijing, China 11 bSchool of Acupuncture-Moxibustion and Tuina, School of Health and Rehabilitation, 12 Nanjing University of Chinese Medicine, Nanjing, China 13 cDepartment of Rehabilitation, The Central Hospital of Wuhan, Tongji Medical 14 College, Huazhong University of Science and Technology, Wuhan, China 15 dDepartment of Acupuncture and Moxibustion, Shenzhen Hospital, Beijing University 16 of Chinese Medicine, Shenzhen, China 17 ePain Medicine Center, Peking University Third Hospital, Beijing, China 18 fDepartment of Acupuncture, Union Hospital, Tongji Medical College, Huazhong 19 University of Science and Technology, Wuhan, China 20 gDepartment of Acupuncture, Affiliated Hospital of Nanjing University of Chinese 21 Medicine, Nanjing, China 22 hDepartment of Acupuncture, Dongzhimen Hospital Affiliated to Beijing University 23 of Chinese Medicine, Beijing, China 24 Corresponding author* 25 Department of Acupuncture, Union Hospital, Tongji Medical College, Huazhong 26 University of Science and Technology, Wuhan, China. No. 1277 Jiefang Avenue, 27 Jianghan District, Wuhan 430022,China. 28 E-mail Address: [email protected] (G.-W. Cai) 29 Corresponding author** 30 International Acupuncture and Moxibustion Innovation Institute, School of 31 Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No.11 32 Bei San Huan Dong Lu, Chaoyang District, Beijing 100021, China. E-mail 33 Address:[email protected] (C.-Z. Liu) 34 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 35 Summary 36 Background Sciatica is a condition including unilateral leg pain that is more severe 37 than low back pain, and causes severe discomfort and functional limitation. We 38 investigated the effect of acupuncture on leg pain in patients with sciatica due to 39 lumbar disc herniation. 40 Methods In this multi-centre, prospective, randomised trial, we enrolled patients with 41 sciatica due to lumbar disc herniation at 6 hospitals in China. Patients were randomly 42 assigned (1:1:1) to receive either acupuncture at the acupoints on the disease-affected 43 meridian (DAM), or the non-affected meridian (NAM), or the sham acupuncture (SA) 44 3 times weekly for 4 weeks. The primary end point was the change in visual analogue 45 scale (VAS, 0-100) of leg pain intensity from baseline to week 4. This study is 46 registered with Chictr.org.cn, ChiCTR2000030680. 47 Finding Between Jun 9th, 2020, and Sep 27th, 2020, 142 patients were assessed for 48 eligibility, 90 patients (30 patients per group) were enrolled and included in the 49 intention-to-treat analysis. A greater reduction of leg pain intensity was observed in 50 the DAM group than in the other groups: -22.2 mm than the SA group (95%CI, -31.4 51 to -13.0, P <0.001) , and -19.3mm than the NAM group (95% CI, -28.4 to -10.1; P 52 <0.001). However, we did not observe a significant difference in the change of leg 53 pain intensity between the NAM group and the SA group (between-group difference 54 -3.0 [95% CI, -12.0 to 6.1], P=0.520). There were no serious adverse events. 55 Interpretation Compared with SA, acupuncture at the acupoints on the 56 disease-affected meridian, but not the non-affected meridian, significantly reduces the 57 leg pain intensity in patients with sciatica due to lumbar disc herniation. These 58 findings suggest that the meridian-based specificity of acupoint is a considerable 59 factor in the acupuncture treatment. A larger, sufficiently powered trial is needed to 60 accurately assess efficacy. 61 62 Funding The National Key R&D Program of China (No: 2019YFC1712103) and the 63 National Science Fund for Distinguished Young Scholars (No:81825024). 64 Keywords: Acupuncture; leg pain; Acupoint selection; Meridian-based; Sciatica 65 66 67 68 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 69 Research in context 70 Evidence before this study 71 Using the key words "sciatica" and "acupuncture"，we searched PubMed for articles 72 published between Jan 1, 1947 and Jan 5, 2024. Despite an extensive literature search, 73 only a limited number of studies were available. There is ambiguous evidence about 74 the use of acupuncture, with most studies contrasting one another in addition to the 75 lack of high-quality trials. Since the choice of more appropriate acupoints for 76 stimulation is meaningful for acupuncture, studies that investigate the effect of 77 acupuncture on different acupoint program are urgently needed. 78 Added value of this study 79 This multi-centre, assessor and statistician-blinded trial addressed the above 80 limitations by showing that, compared with sham acupuncture, acupuncture at the 81 acupoints on the disease-affected meridian, but not the non-affected meridian, 82 significantly reduces the leg pain intensity in patients with sciatica due to lumbar disc 83 herniation. 84 Implications of all the available evidence 85 We found that acupuncture at the acupoint on the disease-affected meridian had 86 superior and clinically relevant benefits in reducing pain intensity to a greater degree 87 than acupuncture at NAM or SA. The finding is of vital significance to clinical work, 88 as meridian-based specificity of acupoint is one of the most determining factors in the 89 efficacy of acupuncture. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 90 Introduction 91 Sciatica is a common health problem in the general population with a lifetime 92 prevalence of 10% to 43%, depending on different etiologies [1-2]. It is characterised 93 by radiating leg pain starting from the low back, at times accompanied by sensory or 94 motor deficits. In most cases, sciatica is attributable to lumbar disk disorders [3]. The 95 overall prognosis is worse than low back pain, particularly if leg pain extends distal to 96 the knee with signs of nerve root compression, increasing risk for unfavorable 97 outcomes and health care use [4]. Spontaneous recovery occurs in most patients; 98 however, many endure substantial pain and prolonged disability, as 34% reported 99 chronic pain beyond 2 years [5-6]. Optimal pharmacological treatment is unclear due 100 to uncertain benefits or high rates of adverse effects[7-8]. Surgery has been 101 demonstrated to ameliorate sciatica in the early stage, but a proportion of patients do 102 not meet surgical standards or hesitate about the potential complications [9]. The 103 dilemma has led to a soaring increase in complementary and alternative medicine, 104 such as acupuncture [10]. 105 Acupuncture has been recommended for management of low back pain by clinical 106 practice guideline from the American College of Physicians [11-12]. Several studies 107 have also shown that acupuncture was beneficial in treating leg pain, although others 108 have reported discrepancies concerning the efficacy of true vs sham acupuncture[10]. 109 The inconsistent findings may result from variations in study design and insufficient 110 sample size. We conducted this trial to preliminarily evaluate the efficacy and safety 111 of acupuncture in terms of reduction in leg pain with sciatica patients. 112 Acupuncture is garnering increased attention as an effective treatment for pain 113 managemengt, one important issue is whether acupoint choice influences the benefits 114 of acupuncture[10]. However, a well-recognized acupoint program has yet not been 115 established, yielding heterogeneous results across relative studies[13]. Therefore, the 116 second aim of this study was to compare the difference of acupuncture efficacy in 117 patients receiving acupuncture at the acupoints of the disease-affected meridian 118 (DAM), the non-affected meridian (NAM), or sham acupuncture (SA). 119 120 Methods 121 Study design and participants 122 This mult-centre, three-arm, prospective randomised trial was conducted in the 123 inpatient departments of 6 tertiary hospitals in China between Jun 9, 2020 and Sep27, This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 124 2020. The study protocol was approved by the local ethics committee at the 125 coordinating center and each study site (No. 2020BZHYLL0105), and registered with 126 the Chinese Clinical Trial Registry on Chictr.org.cn, ChiCTR2000030680. The 127 protocol has been published previously [14] and is available in open-access full text 128 and in Supplement 1. All patients provided written informed consent before 129 enrolment. 130 Eligible patients were aged 18 to 70 years old , reported leg pain extending below 131 the knee in a nerve root distribution over 4 weeks, had a lumbar disc herniation 132 confirmed by examination signs (positive result on straight leg raise test or sensory or 133 motor deficit in a pattern consistent with a lumbar nerve root) [15], and scored 40 mm 134 or higher on the 100-mm VAS [16]. Imaging (magnetic resonance imaging with or 135 without computed tomography) corroborating a root-level lesion concordant with 136 symptoms and/or signs was determined by the trial clinician. Exclusion criteria were a 137 history or diagnostic result that suggested an inherited neuropathy or neuropathy 138 attributable to other causes, had undergone surgery for lumbar disc herniation within 139 the past 6 months or plan to have spinal surgery or other interventional therapies 140 during next 4 weeks, continually took antiepileptic medication, antidepressant 141 medication, opioids or corticosteroids; had cardiovascular, liver, kidney, or 142 hematopoietic system diseases, mental health disorders, other severe coexisting 143 diseases (e.g., cancer), pregnant, breastfeeding, or women planning conception during 144 the study. Patients participating in other clinical studies within the past 3 months or 145 receiving acupuncture within 6 months were also excluded. The screening process 146 was conducted in the way of in-person visits by trial clinicians. 147 Randomisation and masking 148 The study protocol was explained to all enrolled patients before randomisation. 149 After written informed consent was obtained, patients were allocated randomly (1:1:1) 150 to the three arms: DAM, NAM or SA. Randomisation was performed with a random 151 block size of six. A randomisation sequence was created by a biostatistician who did 152 not participate in the implementation or statistical analysis of trial. The assessor and 153 statistician were blinded to treatment allocation throughout data collection and 154 analysis. 155 Procedures and interventions 156 To exploratively observe whether the effects of acupoint located on two kinds of 157 meridians are different, this trial set two acupuncture groups, in which patients This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 158 received acupuncture at acupoints on the disease-affected meridian (DAM), or the 159 non-affected meridian (NAM), respectively. The bladder (BL) and gallbladder (GB) 160 meridians are directly in the same dermatomes of the sciatic nerve. Since these 161 meridians are consistent with sciatic pain distribution, they are regarded as the 162 disease-affected meridians. 163 Patients assigned to the DAM group received semi-standardized treatment at 164 acupoints on the bladder/gallbladder meridians. Bilateral BL25 and BL26, which 165 localized at the same level as the inferior border of the spinous process of the fourth 166 and the fifth lumbar vertebra (the commonest positions of disc rupture), were needled 167 as obligatory acupoints. For those having symptoms at the posterior side of the leg, 168 BL54, BL36, BL40, BL57, and BL60 were needled as adjunctive acupoints; similarly, 169 GB30, GB31, GB33, GB34, and GB39 were adjunctive acupoints for patients with 170 symptoms at lateral side. For patients who had pain at both posterior and lateral sides, 171 acupuncturists were instructed to select 5 of the 10 adjunctive acupoints. 172 According to the principle of the Traditional Chinese Medicine theory, the liver 173 meridian, the spleen meridian, and the kidney meridian are commonly treated to 174 improve the functional status of the body. These meridians distribute at the inner side, 175 less related to sciatica symptoms, and are regarded as non-affected meridians. For 176 patients in the NAM group, bilateral EX-B7, EX-B4, and unilateral LR9, LR8, LR5, 177 KI7, and SP4 that on the non-affected meridians were selected . 178 Patients assigned to the SA group received acupuncture at 7 non-acupoints which 179 not localized on meridians and with no manipulations. 180 All acupuncture treatments were performed by two senior acupuncturists (length of 181 services ≥5 years), who consistently applied the same standardised protocols. After 182 identifying the location of acupoints, sterile acupuncture needles (length 40 mm, 183 diameter 0.30 mm; Hwato, Suzhou Medical Appliance Factory, China) were inserted, 184 followed by 30s manipulation to acquire Deqi (a sensation of aching, soreness, 185 swelling, heaviness, or numbness). Blunt-tipped placebo needles with similar 186 appearances to conventional needles but no skin penetration were used in the SA 187 group. To maximize the blinding of patients and to fix blunt-tipped placebo needles, 188 adhesive pads were placed on points in all groups. Patients in all groups started 189 treatment on the day of randomization and received twelve 30-minute sessions over 4 190 consecutive weeks at 3 sessions per week (ideally every other day). This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 191 Pain medication was offered if necessary and included paracetamol and optionally 192 non-steroidal anti-inflammatory drugs (Celebrex), short acting opioids, or both. We 193 used questionnaires to monitor the use of pain medication and other co-interventions. 194 Outcomes 195 The primary outcome was the change of leg pain intensity over the preceding 24 196 hours from baseline to week 4 as measured on the VAS. Participants were asked to 197 rate their average leg pain during the last 24 hours out of 100, with 0 representing no 198 leg pain and 100 representing the worst pain imaginable. 199 Secondary outcomes included VAS for leg pain and back pain intensity at other 200 time points. We observed the Oswestry Disability Index (ODI, examining perceived 201 functional disability in 10 activities of daily living), Sciatica Frequency and 202 Bothersomeness Index (SFBI, rating the extent of frequency and bothersomeness of 203 sciatica respectively), 36-item Short Form Health Survey (SF-36, evaluating the 204 quality of life with physical and mental components) . 205 We also assessed levels on the global perceived recovery (assessed by a 7-point 206 Likert self-rating scale with options from “completely recovered” to “worse than 207 ever”) and degrees of the straight leg raise test. 208 The Credibility/Expectancy Questionnaire (CEQ) was used to assess the credibility 209 and expectancy of patients to acupuncture treatment after the first treatment. 210 Moreover, patients were also invited to guess their group for blinding assessment at 211 week 2 and week 4. Adverse events were documented by patients and outcome 212 assessors throughout the trial. All adverse events were categorized as 213 treatment-related or non-treatment-related and followed up until resolution. 214 The researchers in charge of the scale assessment were asked to use the fixed 215 guiding words on the questionnaires to have a conversation with the patient without 216 redundant communication. Due to the trial site and population, we used Chinese 217 versions of the assessment scales that were confirmed to have moderate or higher 218 clinical responsiveness and are suitable for clinical efficacy evaluation. 219 Statistical analysis 220 We designed our trial to determine whether there was a difference between each 221 acupuncture group and the sham acupuncture group in terms of leg pain intensity. 222 According to the method of upper confidence limit, a sample size ranging from 20 to 223 40 could be the guideline for choosing the size of a pilot sample. Considering the 224 overall resource input issues (eg, funding availability and expected completion time), This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 225 the total sample size was preset at 90 patients, 30 patients per group. We performed 226 analyses following the intention-to-treat principle with all randomly assigned patients 227 included. 228 For the primary outcome, analysis of covariance was applied to test the difference 229 between groups in leg pain intensity with baseline values adjusted. Missing data were 230 imputed using multiple imputation method. To address the robustness of the results, 231 we performed a per-protocol analysis for the primary outcome, covering patients who 232 complete 10 sessions or more and had no major protocol violations (e.g., using 233 additional treatments during the treatment period). One-way ANOVA was performed 234 for the secondary outcomes including leg pain at each measuring time point, back 235 pain, ODI, SFBI, SF-36, CEQ, PDQ, global perceived recovery scores, and degrees of 236 straight leg raise test. The blinding assessment, the proportion of patients using 237 additional treatments and adverse event rates were analyzed using the χ2 test or Fisher 238 exact test. Between-group differences were tested through the least significance 239 difference (LSD)-t test. Categorical variables are presented as n (%) and continuous 240 variables are presented as the mean (SD) or median (interquartile range, IQR) . All 241 tests applied were two-tailed, p < 0.05 was considered statistically significant. An 242 independent statistician completed the analyses using IBM SPSS Statistics version 20 243 (IBM Corp, Armonk, NY). 244 Role of the funding source 245 The funder of the study had no role in the study design, data collection, data 246 analysis, or writing of the report. All authors had full access to the data in the study 247 and gave the final approval of the manuscript and agree to be accountable for all 248 aspects of work. 249 Results 250 Patient characteristics 251 Between Jun 9th, 2020, and Sep 27th, 2020, 142 patients were assessed for 252 eligibility, 90 patients (30 patients per group) were enrolled and included in the 253 intention-to-treat analysis (Figure 1). Mean age of patients was 44.2 (SD 14.9) years, 254 and 51 (56.7%) were female. Mean symptom duration was 2.0 years (IQR 0.7 to 4.1) 255 with a mean VAS score of 62.3 (SD 14.3) mm for their leg pain intensity. Overall, 75 256 (83.3%) patients completed the assigned 12 sessions of study interventions, and 82 257 (91.1%) received at least 10 sessions. The primary outcome visit was attended by 82 258 patients at week 4, corresponding to a follow-up rate of 91.1%, which was maintained This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 259 to week 26. There was no difference among groups regarding the usual risk factors for 260 sciatica, such as gender, age, body-mass index, or Disk herniation level, which 261 confirmed that the groups were well matched. The baseline characteristics of patients 262 are summarized in Table 1. 263 After receiving 4-week treatment, the change of leg pain intensity decreased by 264 -36.6 mm (95% CI, -43.1 to -30.2) in the DAM group, by -17.4 mm in the NAM 265 group and by -14.4 mm (95% CI, -20.9 to -8.0) in the SA group. Changes in the leg 266 pain intensity over 4-week period differed significantly among the 3 groups. A greater 267 reduction was observed in the DAM group than in the other groups: -22.2 mm 268 reduction in leg pain intensity than in the SA group (95% CI, -31.4 to -13.0, P＜ 269 0.001) , and -19.3 mm reduction in leg pain intensity than in the NAM group (95% CI, 270 -28.4 to -10.1; P <0.001). While no significant change in leg pain intensity was 271 observed between the NAM and SA groups (mean difference, -3.0 mm, 95% CI, -12.0 272 to 6.1, P=0.52) (Figure 2). 273 We observed that outcomes at the 26-week follow-up were similar in direction to 274 the those at the end of an 4-week period. At week 26, a difference in the change of leg 275 pain intensity were present between the DAM and SA groups (mean difference, -13.3 276 mm, 95% CI, -23.2 to -2.8, P=0.01), between the DAM and NAM groups (mean 277 difference, -13.4 mm, 95%CI, -23.6 to -3.1, P=0.011), but not between the NAM and 278 SA groups (mean difference, 0.1 mm, 95% CI, -10.3 to 10.5, P=0.99) (Figure 2). 279 Sensitive analyses did not alter the result in the primary analysis (eTable 1 and eTable 280 2 in Supplement 2). 281 We found a greater reduction in back pain intensity over SA for patients who 282 received DAM at week 4 (mean difference, -18.0 mm, 95% CI, -27.7 to -8.4, P＜ 283 0.001). The difference in back pain changes was not significant between the NAM 284 and SA groups at week 4 (mean difference, -4.2 mm, 95% CI, -13.6 to 5.3, P=0.38). 285 At week 26, no difference was detected in back pain relief across the 3 groups. 286 We also found a greater decrease in disability scores in the DAM group over SA at 287 week 4 (mean difference, -10.7 points, 95% CI, -18.3 to -3.1, P=0.007), while there 288 was no difference between the NAM and SA groups (mean difference, -3.1 points, 289 95%CI, -10.6 to 4.3, P=0.41). Similar results were observed at week 26, which 290 favored acupuncture at DAM (mean difference between DAM and SA, -11.1 points, This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 291 95%CI, -19.4 to -2.8, P=0.01) rather than acupuncture at the NAM (mean difference 292 between NAM and SA, -2.7 points, 95%CI, -11.0 to -5.7, P=0.53). 293 Compared to SA, patients in the DAM group reported better symptom 294 improvement on the global perceived recovery test, and lower scores in both 295 frequency and bothersomeness scales on the SFBI. Nonetheless, the measurement of 296 the quality of life, or the degree of the straight leg raise test did not show a difference 297 across the 3 groups (Table 2). Five (16.7%) patients in the DAM group and 4 (13.3%) 298 patients in the SA group take rescue medicine for a short period (eTable 3 in 299 Supplement 2). For blinding assessment, we found no difference across groups in the 300 proportion of patients who correctly guessed the kind of intervention they had 301 received at week 2 and week 4 (eTable 4 in Supplement 2). Outcomes measured at 302 other time points were shown in eTable 5 and e Figure in Supplement 2. 303 Adverse events 304 Three (10%) patients in the NAM group reported post-needling pain which 305 decreased in the following week spontaneously. Adverse events unrelated to the study 306 interventions including increased leg pain, dizziness, insomnia, etc, were all rated as 307 mild to moderate (eTable 6 in Supplement 2). No serious adverse event occurred 308 during the study period. 309 Interpretation 310 To our knowledge, our study is a multi-center clinical trial to show the beneficial 311 effect of acupuncture for patients with moderate-to-severe sciatica of varying duration 312 and is the first to explore the meridian-based acupoint program in this field. We found 313 that acupuncture at the DAM had superior and clinically relevant benefits in reducing 314 leg pain intensity to a greater degree than acupuncture at NAM or SA. Improvements 315 in functional disability, back pain, frequency and bothersomeness and global 316 perceived recovery were also found. Moreover, no significant differences was 317 observed with respect to any outcome between NAM and SA groups. 318 The findings of the current study demonstrate that acupuncture at the acupoints on 319 the disease-affected meridian was clinically beneficial and superior to SA for leg pain. 320 We acknowledge the commonly recognised minimally clinically important difference 321 (MCID) is 10-20 of 100 for pain intensity [16]. The clinically important mean leg 322 pain reduction at the 4-week of treatment in DAM group was -22.2 mm, and 323 continued the trend of a mean clinical important result at 26-week follow-up (-13.3 324 mm). Before our study, Liu and colleagues evaluated the effect of acupuncture in This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 325 relieving leg pain for patients with chronic discogenic sciatica compared with sham 326 acupuncture [13]. Acupuncture showed a small but not clinically relevant effect, with 327 a between-group difference in the 4-week on mean VAS score for leg pain was 7.28， 328 which is not reach the MCID. More acupoints on the disease-affected meridian were 329 adapted in our trial (7 v 4 acupoints on the bladder and/or the gallbladder meridian) 330 which may interpret the discrepancy. 331 Our findings are consistent with a meta-analysis showing that acupuncture was 332 more effective than conventional medicine in managing the pain associated with 333 sciatica, with a significantly greater reduction in pain intensity by 12.5 (95% CI: 334 −16.3 to −8.6) [17]. It is worth noting that the most commonly used acupoints were 335 Huantiao (GB 32), Weizhong (BL 40), and Yanglingquan (GB 34), all on the bladder 336 and/or gallbladder meridians that were directly related with dermatomal distributions 337 of sciatic nerve. Acupuncture at the DAM was more effective than at the NAM in 338 alleviating pain severity during the 4-week treatment and the follow-up period. The 339 acupoints in NAM group are mainly located on the Liver, Spleen and Kidney 340 meridian, which are not affected directly by sciatica in Traditional Chinese Medicine. 341 We speculate that the varied efficacy between the DAM and NAM relate to 342 meridian-based acupoint specificity. 343 Acupuncture at the DAM showed significant superiority in the primary outcome 344 and in most of the second outcomes at the end of therapy. However, no significant 345 differences were observed in the quality of life or the degree of the straight leg raise 346 test among the three groups. The health status and body function are more likely be 347 affected by physical factors and psychological factors [18-19]. In addition, pain may 348 limit function, so as pain decreases, function (straight leg raise) may increase until 349 pain again limits functional capacity. This may explain the improvement in pain 350 without measurable proved function [20]. 351 In Dr. Vickers’ and his groups 2018 update of the meta-analysis of acupuncture for 352 chronic pain study, the authors did not finding any statistically significant influence 353 from point selection on treatment outcome by acupuncture [11]. Another two clinical 354 trials on acupuncture for low back pain, where the first showed no difference between 355 two different acupuncture recipes [21] and the subsequent detected no difference 356 between and real and sham acupuncture (where the sham treatment involved different 357 bodily locations) [22]. The efficacy of acupuncture is related to the dose, point This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 358 selection and treatment time (duration and frequency), and we could not isolate which 359 components contributed to the benefits. Our study only partially answer that acupoint 360 choice could influence the efficacy of acupuncture. 361 Practice guidelines recommend an initial period of conservative care focused on 362 non-pharmacologic treatments for persons with recent-onset sciatica, except in rare 363 instances of rapidly progressing or severe neurologic deficits that may require 364 immediate surgical intervention. In this study, acupuncture hastened pain and 365 functional improvement, indicating that acupuncture could be offered to patients with 366 sciatica lasting at least 4 weeks (mean duration of 2.0 years) as promising 367 non-pharmacologic care. However, prior studies enrolled patients with more acute 368 conditions who may have been more prone to spontaneous recovery than our 369 participants, which limit the generalizability of the trial findings. 370 Acupuncture has regionally specific effect or segmental effect [23-24]. Acupoints 371 located directly on injured nerves could inhibit the nociceptive pathway at the same 372 spinal level and give an analgesic effect at the same dermatomal level [25]. However, 373 the underlying mechanism is not fully elucidated and is worthy of further study. 374 This study had several strengths. Rigorous methods have been used to test the 375 preliminary efficacy of acupuncture in this pilot study. The use of blunt-tipped 376 placebo needles ensured the implementation of blinding, which can make the patients 377 have the feeling of acupuncture under the premise that the needle tip does not 378 penetrate the skin. The high recruitment rate has reflected the willingness to 379 participate among patients with sciatica. The compliance rate (83.3%) and follow-up 380 rate (91.1%) for this pilot trial are satisfactory. Therefore, the current study may 381 provide a more accurate basis for assessing the sample size and selection of 382 acupuncture acupoints for the large-scale trial to be conducted. 383 Limitations 384 Some limitations have to be acknowledged. First, we run this multi-center trial in 385 order to text the feasiblity to implement a large-scale RCT to further confirm the 386 efficacy of acupuncture in this regard. However, with only 90 participants spread over 387 six centers, the effect from the numerous treatment centers should be probably 388 accounted. Second, due to the nature of acupuncture, it was not possible to blind 389 acupuncturists to treatment assignment. But they were trained in advance to follow a 390 standard operating procedure and keep equal communication with patients. Third, 391 although sensitive analysis indicated similar conclusions, the robustness of our This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 392 finding was decreased by the small sample size with a wide credible interval 393 generated, thus further studies with sufficient sample size are needed. Fourth, a 394 treatment that offered 3 sessions per week for continuous 4 weeks was proposed to be 395 burdensome for part of the patients, especially for those who are employed. Treatment 396 with a gradually decreased frequency should be applied in future studies. 397 Conclusion 398 Acupuncture was safely administered in patients with mild to moderate sciatica 399 caused by lumbar disc herniation. To accurately assess the efficacy, a larger, 400 sufficiently powered trial is needed. Acupuncture at the acupoint on the 401 disease-affected meridian had superior and clinically relevant benefits in reducing 402 pain intensity to a greater degree than acupuncture at NAM or SA. Data supported the 403 meridian-based specificity of acupoint is one of the most determining factors in the 404 efficacy of acupuncture. 405 406 References 407 1. Gadjradj PS, Rubinstein SM, Peul WC, et al. Full endoscopic versus open 408 discectomy for sciatica: randomised controlled non-inferiority trial. BMJ. 2022; 409 376:e065846. 410 2. Konstantinou K, Dunn KM. Sciatica: review of epidemiological studies and 411 prevalence estimates. Spine. 2008; 33:2464-2472. 412 3. Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ. 413 2007; 334:1313-1317. 414 4. Deyo RA, Mirza SK. Herniated Lumbar Intervertebral Disk. N Engl J Med. 2016; 415 374:1763-1772. 416 5. Ropper AH, Zafonte RD. Sciatica. 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Diagnosis and treatment of sciatica. 442 BMJ 2019;367:l6273. 443 16. Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: 444 what is moderate pain in millimetres? Pain. 1997;72:95-7. 445 17. Schroeder K, Richards S. Non-specific low back pain. Lancet 2012;379:482-91 446 18. Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of context 447 effects on health outcomes: A systematic review. Lancet 448 2001;357(9258):757-762 449 19. Ropper AH, Zafonte RD. Sciatica. New Engl J Med 2015;372(13):1225–1240. 450 20. Cherkin DC, Sherman KJ, Avins AL, Erro JH, Ichikawa L, Barlow WE, Delaney 451 K, Hawkes R, Hamilton L, Pressman A, Khalsa PS, Deyo RA. A randomized trial 452 comparing acupuncture, simulated acupuncture, and usual care for chronic low 453 back pain. Arch Intern Med. 2009;169(9):858-866. 454 21. Donna Kalauokalani, Daniel C Cherkin, Karen J Sherman. A comparison of 455 physician and nonphysician acupuncture treatment for chronic low back pain. 456 Clin J Pain. 2005;21(5):406-411. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 457 22. Goldberg H, Firtch W, Tyburski M, et al. Oral steroids for acute radiculopathy 458 due to a herniated lumbar disk: a randomized clinical trial. JAMA. 459 2015;313:1915-1923. 460 23. Zhang R, Lao L, Ren K, Berman B. Mechanisms of 461 acupuncture-electroacupuncture on persistent pain. Anesthesiology. 462 2014;120(2):482-503. 463 24. Cheng K. Neuroanatomical basis of acupuncture treatment for some common 464 illnesses. Acupunct Med. 2009;27(2):61-4. 465 25. Cheng KJ. Neuroanatomical basis of acupuncture treatment for some common 466 illnesses. Acupuncture in medicine: journal of the British Medical Acupuncture 467 Society. 2009;27:61-64. 468 469 Figure legends 470 Figure 1. Modified CONSORT flow diagram. 471 Figure 2. VAS scores for leg pain intensity. 472 Tables 473 Table 1. Baseline characteristics of participants. 474 Table 2. Primary and secondary outcomes measured at week 4 and week 26. 475 476 Contributors 477 CZL is the guarantor for the article. CZL, GXS and FTY designed the trial. GWC, 478 GXN, WJW, XQZ, and XLM offered administrative support. FTY, HCX, HYF, LT, 479 BZ, and XLJ recruited and followed up patients. LQW, JFT and JWY were 480 responsible for study monitoring. SYY and JWY take responsibility for the accuracy 481 of the data analysis. All authors had full access to the data in the study and gave the 482 final approval of the manuscript and agree to be accountable for all aspects of work. 483 484 Data sharing statement 485 Data are available from the corresponding author on reasonable request. 486 Declaration of interests 487 The authors declare no conflict of interest. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed Figure 1. Modified CONSORT flow diagram. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed Figure 2. VAS scores for leg pain intensity. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 1 Table 1. Baseline characteristics of participants. Characteristic DAM group (n=30) NAM group (n=30) SA group (n=30) Age, year, mean (SD) 41.6 (14.7) 44.8 (15.0) 46.1 (15.1) Sex, no. (%) Female 21 (70.0) 16 (53.3) 14 (46.7) Male 9 (30.0) 14 (46.7) 16 (53.3) Marital status, no. (%) Married 22 (73.3) 23 (76.7) 24 (80.0) Single 8 (26.7) 7 (23.3) 6 (20.0) Occupation, no. (%) Mental work 24 (80.0) 24 (80.0) 20 (66.7) Manual work 6 (20.0) 6 (20.0) 10 (33.3) BMI, kg/m2, mean (SD) 22.6 (3.1) 23.3 (2.5) 23.0 (2.7) Duration of sciatica, year, median (IQR) 1.7 (0.4, 5.0) 1.8 (0.7, 3.3) 2.1 (0.7, 6.3) History of acupuncture, no. (%) Yes 13 (43.3) 15 (50.0) 9 (30.0) No 17 (56.7) 15 (50.0) 21 (70.0) Positive straight leg raise test, no. (%) 12 (40.0) 19 (63.3) 16 (53.3) Numbness, no. (%) 20 (66.7) 17 (56.7) 23 (76.7) Tingling, no. (%) 17 (56.7) 21 (70.0) 17 (56.7) Sensory deficit, no. (%) 4 (13.3) 3 (10.0) 3 (10.0) Muscle weakness, no. (%) 8 (26.7) 8 (26.7) 8 (26.7) This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 2 Reflex changes, no. (%) 1 (3.3) 1 (3.3) 1 (3.3) Disk herniation level, no. (%) L3-L4 2 (6.7) 0 (0.0) 0 (0.0) L4-L5 6 (20.0) 14 (46.7) 7 (23.3) L5-S1 9 (30.0) 4 (13.3) 8 (26.7) More than one level 13 (43.3) 12 (40.0) 15 (50.0) Leg pain intensity*, mm, mean (SD) 59.5 (12.3) 63.2 (14.8) 64.3 (15.7) Back pain intensity*, mm, mean (SD) 58.9 (25.2) 56.2 (23.6) 54.6 (26.0) ODI score†, mean (SD) 38.3 (13.0) 38.0 (15.7) 38.2 (14.8) SFBI score‡, mean (SD) Frequency 13.7 (4.4) 14.5 (4.5) 13.7 (5.2) Bothersomeness 12.3 (3.6) 12.5 (3.9) 12.9 (5.0) SF-36 score§, mean (SD) Physical Component 28.5 (10.4) 33.5 (11.5) 31.0 (10.3) Mental Component 52.4 (12.1) 47.6 (15.3) 49.9 (13.1) PDQ score¶, mean (SD) 10.5 (5.5) 12.3 (5.4) 10.7 (6.3) Credibility score**, mean (SD) 0.3 (2.5) 0 (2.6) -0.3 (2.8) Expectancy score**, mean (SD) 0.5 (2.6) -0.4 (3.0) -0.1 (2.7) * Scores range from 0 to 100, with higher scores indicating more severe pain. † Scores range from 0 to 100, with higher scores indicating worse disability. ‡ Scores range from 0 to 24, with higher scores indicating more severe symptoms. § Scores are based on normative data and have a mean (±SD) of 50±10, with higher scores indicating a better This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 3 quality of life. ¶ Scores range from 0 to 30, with higher scores indicating more neuropathic pain. ** Scale has Mean = 0.0 (SD = 1.0) since the items were converted to z-scores before averaging. DAM, the disease-affected meridian; NAM, the non-affected meridian; SA, Sham acupuncture. SD, standard deviation; IQR, interquartile range; BMI, body mass index; ODI, Oswestry Disability Index; SFBI, Sciatica Frequency and Bothersomeness Index; SF-36, 36-item Short Form Health Survey; PDQ, PainDETECT questionnaire. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 4 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 1 Table 2. Primary and secondary outcomes at week 4 and week 26 DAM vs SA NAM vs SA DAM vs NAM Outcome DAM group NAM group SA group P value Difference P value Difference P value Difference P value Primary outcome Change of leg pain intensity at week 4* -36.6 (-43.1, -30.2) -17.4 (-23.8, -11.0) -14.4 (-20.9, -8.0) ＜0.001 -22.2 (-31.4, -13.0) ＜0.001 -3.0 (-12.0, 6.1) 0.520 -19.3 (-28.4, -10.1) ＜0.001 Secondary outcomes Change of leg pain intensity at week 26‡ -35.5 (-42.8, –28.3) -22.2 (-29.3, -15.0) -22.2 (-29.7, -14.7) 0.016 -13.3 (-23.2, -2.8) 0.014 0.1 (-10.3, -10.5) 0.989 -13.4 (-23.6, -3.1) 0.011 Change of back pain intensity Week 4† -34.9 (-41.7, -28.2) -21.1 (-27.6, -14.6) -16.9 (-23.8, -10.0) 0.001 -18.0 (-27.7, -8.4) ＜0.001 -4.2 (-13.6, 5.3) 0.380 -13.8 (-23.2, -4.5) 0.004 Week 26‡ -33.5 (-41.6, -25.4) -23.6 (-31.8, -15.5) -22.7 (-31.1, -14.2) 0.128 -10.8 (-22.6, 0.9) 0.07 -1.0 (-12.7, 10.8) 0.871 -9.9 (-21.4, -1.6) 0.092 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 2 ODI score Week 4† 18.0 (13.9, 22.1) 25.5 (19.6, 31.5) 28.7 (22.6, 34.7) 0.019 -10.7 (-18.3, -3.1) 0.007 -3.1 (-10.6, 4.3) 0.406 -7.5 (-14.9, -0.1) 0.046 Week 26‡ 14.9 (10.0, 19.8) 23.3 (17.1, 29.5) 26.0 (19.1, 32.8) 0.025 -11.1 (-19.4, -2.8) 0.010 -2.7 (-11.0, 5.7) 0.527 -8.4 (-16.6, -0.3) 0.043 SFBI frequency score Week 4† 6.6 (4.9, 8.4) 10.6 (8.7, 12.5) 10.8 (8.5, 13.1) 0.005 -4.1 (-6.9, -1.4) 0.004 -0.2 (-2.9, 2.5) 0.874 -3.9 (-6.6, -1.2) 0.005 Week 26‡ 5.8 (3.7, 7.8) 10.1 (7.8, 12.5) 10.0 (7.4, 12.5) 0.010 -4.2 (-7.4, -1.0) 0.011 0.2 (-3.1, 3.4) 0.928 -4.4 (-7.5, -1.2) 0.007 SFBI bothersomeness score Week 4† 5.6 (4.0, 7.1) 8.9 (7.2, 10.6) 10.2 (8.1, 12.2) 0.001 -4.6 (-7.1, -2.1) ＜0.001 -1.3 (-3.7, 1.2) 0.306 -3.3 (-5.8, -0.9) 0.007 Week 26‡ 4.9 (3.2, 6.6) 8.5 (6.5, 10.5) 9.0 (6.6, 11.4) 0.007 -4.1 (-6.9, -1.3) 0.004 -0.5 (-3.3, 2.3) 0.742 -3.7 (-6.4, -0.9) 0.009 SF-36 physical component score Week 4† 37.3 (32.8, 41.7) 37.7 (33.7, 41.6) 33.8 (28.9, 38.7) 0.390 3.5 (-2.7, 9.6) 0.268 3.9 (-2.2, 9.9) 0.206 -0.4 (-6.4, 5.6) 0.888 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 3 Week 26§ 44.7 (39.9, 49.4) 40.1 (35.3, 44.8) 37.4 (32.0, 42.8) 0.104 7.3 (0.4, 14.2) 0.038 2.7 (-4.2, 9.5) 0.443 4.6 (-2.0, 11.3) 0.166 SF-36 mental component score Week 4† 53.7 (49.7, 57.6) 48.6 (43.2, 54.0) 51.9 (47.2, 56.7) 0.287 1.8 (-4.9, 8.4) 0.600 -3.3 (-9.9, 3.2) 0.314 5.1 (-1.4, 11.6) 0.122 Week 26§ 55.1 (51.7, 58.4) 51.2 (46.0, 56.4) 53.3 (48.6, 58.1) 0.438 1.7 (-4.5, 8.0) 0.580 -2.1 (-8.4, 4.1) 0.496 3.9 (-2.1, 9.8) 0.201 Degree of straight leg raise test Week 4¶ 70.1 (63.8, 76.5) 67.2 (61.0, 73.4) 68.5 (61.6, 75.3) 0.797 1.7 (-7.3, 10.6) 0.708 -1.3 (-10.1, 7.6) 0.774 3.0 (-5.8, 11.7) 0.502 Week 26** 74.9 (70.7, 79.1) 70.3 (62.7, 77.9) 69.8 (64.1, 75.4) 0.402 5.1 (-3.2, 13.4) 0.222 0.5 (-7.7, 8.7) 0.902 4.6 (-3.6, 12.8) 0.267 PDQ score Week 4† 6.7 (4.4, 9.2) 9.3 (7.8, 10.8) 8.0 (5.8, 10.2) 0.193 -2.5 (-5.3, 0.2) 0.071 1.3 (-1.5, 4.1) 0.351 -1.2 (-4.1, 1.6) 0.392 Week 26‡ 4.9 (3.3, 6.4) 9.0 (7.7, 10.4) 8.1 (6.0, 10.1) 0.001 -4.1 (-6.4, -1.9) ＜0.001 1.0 (-1.3, 3.3) 0.408 -3.2 (-5.5, -0.9) 0.007 Global perceived This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 4 recovery Week 4† 1.5 (1.2, 1.9) 2.6 (2.1, 3.1) 2.9 (2.4, 3.5) ＜0.001 -1.4 (-2.1, -0.7) ＜0.001 -0.3 (-1.0, 0.3) 0.301 -1.1 (-1.7, -0.4) 0.001 Week 26‡ 1.8 (1.4, 2.2) 2.6 (2.1, 3.0) 2.8 (2.3, 3.3) 0.005 -1.0 (-1.7, -0.4) 0.002 -0.2 (-0.9, 0.4) 0.460 -0.8 (-1.4, -0.2) 0.014 Estimates are expressed as mean (95%CI). * Data imputed through the last observation carried forward approach. † The number of participants providing data was 27 in the DAM group, 29 in the NAM group and 26 in the SA group at week 4. ‡ The number of participants providing data was 28 in the DAM group, 28 in the NAM group and 26 in the SA group at week 26. §The number of participants providing data was 28 in the DAM group, 28 in the NAM group and 24 in the SA group at week 26. ¶ The number of participants providing data was 27 in the DAM group, 28 in the NAM group and 26 in the SA group at week 4. ** The number of participants providing data was 25 in the DAM group, 26 in the NAM group and 25 in the SA group at week 26. DAM, the disease-affected meridian; NAM, the non-affected meridian; SA, Sham acupuncture. ODI, Oswestry Disability Index; SFBI, Sciatica Frequency and Bothersomeness Index; SF-36, 36-item Short Form Health Survey; PDQ, PainDETECT questionnaire. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed 5 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4723062 Preprint not peer reviewed

Only give responses with information found in the text below. Limit your response to 200 words or less. Focus on historical significance that could be linked to current practices. Keep in the style of formal writing for a college institution.

What were the negatives of having such low biodiversity for the coffee plant?

Context: tall bushes to promote branching and the production of new leaves, as well as to facilitate plucking them. Various processing methods are used to attain different levels of oxidation and produce certain kinds of tea, such as black, white, oolong, green, and pu’erh. Basic processing includes plucking, withering (to wilt and soften the leaves), rolling (to shape the leaves and slow drying), oxidizing, and drying. However, depending on the tea type, some steps are repeated or omitted. For example, green tea is made by withering and rolling leaves at a low heat, and oxidation is skipped; for oolong, rolling and oxidizing are performed repeatedly; and for black, extensive oxidation (fermentation) is employed. 3.5.1 The Discovery of Tea Tea was discovered in 2700 BCE by the ancient Chinese emperor Shen Nung, who had a keen interest in herbal medicine and introduced the practice of drinking boiled water to prevent stomach ailments. According to legend, once, when the emperor camped in a forest during one of his excursions, his servants set up a pot of boiling water under a tree. A fragrance attracted his attention, and he found that a few dry leaves from the tree had Colonial Agriculture | 53 fallen accidentally into the boiling pot and changed the color of the water; this was the source of the aroma. He took a few sips of that water and noticed its stimulative effect instantly. The emperor experimented with the leaves of that tree, now called Camellia sinensis, and thus the drink “cha” came into existence. Initially, it was used as a tonic, but it became a popular beverage around 350 BCE. The historian Lu Yu of the Tang dynasty (618–907 CE) has written a poetry book on tea called Cha jing (The Classic of Tea) that contains a detailed description of how to cultivate, process, and brew tea. Tea spread to Japan and Korea in the seventh century thanks to Buddhist monks, and drinking it became an essential cultural ritual. Formal tea ceremonies soon began. However, tea reached other countries only after the sixteenth century. In 1557, the Portuguese established their first trading center in Macau, and the Dutch soon followed suit. In 1610, some Dutch traders in Macau took tea back to the Dutch royal family as a gift. The royal family took an immediate liking to it. When the Dutch princess Catherine of Braganza married King Charles II of England around 1650, she introduced tea to England. Tea passed from the royal family to the nobles, but for an extended period, it remained unknown and unaffordable to common folks in Europe. The supply of tea in Europe was scant and very costly: one pound of tea was equal to nine months’ wages for a British laborer. As European trade with China increased, more tea reached Europe, and consumption of tea increased proportionally. For example, in 1680, Britain imported a hundred pounds of tea; however, in 1700, it brought in a million. The British government allowed the British East India Company to monopolize the trade, and by 1785, the company was buying 15 million pounds of tea from China annually and selling it worldwide. Eventually, in the early eighteenth century, tea reached the homes of British commoners. 3.5.2 Tea and the “Opium War” China was self-sufficient; its people wanted nothing from Europe in exchange for tea. But in Europe, the demand for tea increased rapidly in the mid-eighteenth century. Large quantities were being purchased, and Europeans had to pay in silver and gold. The East India Company was buying so much of it that it caused a crisis for the mercantilist British economy. The company came up with a plan to buy tea in exchange for opium instead of gold and silver. Although opium was banned within China, it was in demand and sold at very high prices on the black market. After the Battle of Plassey in 1757, several northern provinces in India came under the control of the East India Company, and the company began cultivating poppy in Bengal, Bihar, Orissa, and eastern Uttar Pradesh. Such cultivation was compulsory, and the 54 | Colonial Agriculture company also banned farmers from growing grain and built opium factories in Patna and Banaras. The opium was then transported to Calcutta for auction before British ships carried it to the Chinese border. The East India Company also helped set up an extensive network of opium smugglers in China, who then transported opium domestically and sold it on the black market. After the successful establishment of this smuggling network, British ships bought tea on credit at the port of Canton (now Guangzhou), China, and later paid for it with opium in Calcutta (now Kolkata). The company not only acquired the tea that was so in demand but also started making huge profits from selling opium. This mixed business of opium and tea began to strengthen the British economy and made it easier for the British to become front-runners among the European powers. By the 1830s, British traders were selling 1,400 tons of opium to China every year, and as a result, a large number of Chinese became opium addicts. The Chinese government began a crackdown on smugglers and further tightened the laws related to opium, and in 1838, it imposed death sentences on opium smugglers. Furthermore, despite immense pressure from the East India Company to allow the open trading of opium, the Chinese emperor would not capitulate. However, that did not curb his subjects’ addiction and the growing demand for opium. In 1839, by order of the Chinese emperor, a British ship was detained in the port of Canton, and the opium therein was destroyed. The British government asked the Chinese emperor to apologize and demanded compensation; he refused. British retaliated by attacking a number of Chinese ports and coastal cities. China could not compete with Britain’s state-of- the-art weapons, and defeated, China accepted the terms of the Treaty of Nanjing in 1842 and the Treaty of Bog in 1843, which opened the ports of Canton, Fujian, and Shanghai, among others, to British merchants and other Europeans. In 1856, another small war broke out between China and Britain, which ended with a treaty that made the sale of opium legal and allowed Christian missionaries to operate in China. But the tension between China and Europe remained. In 1859, the British and French seized Beijing and burned the royal Summer Palace. The subsequent Beijing Convention of 1860 ended China’s sovereignty, and the British gained a monopoly on the tea trade. 3.5.3 The Co-option of Tea and the Establishment of Plantations in European Colonies Unlike the British, the Dutch, Portuguese, and French had less success in the tea trade. To overcome British domination, the Portuguese planned to develop tea gardens outside China. Camellia is native to China, and it was not found in any other country. There was Colonial Agriculture | 55 a law against taking these plants out of the country, and the method for processing tea was also a trade secret. In the mid-eighteenth century, many Europeans smuggled the seeds and plants from China, but they were unable to grow them. Then, in 1750, the Portuguese smuggled the Camellia plants and some trained specialists out of China and succeeded in establishing tea gardens in the mountainous regions of the Azores Islands, which have a climate favorable for tea cultivation. With the help of Chinese laborers and experts, black and green tea were successfully produced in the Portuguese tea plantations. Soon, Portugal and its colonies no longer needed to import tea at all. As the owners of the first tea plantations outside China, the Portuguese remained vigilant in protecting their monopoly. It was some time before other European powers gained the ability to grow and process tea themselves. In the early nineteenth century, the British began exploring the idea of planting tea saplings in India. In 1824, Robert Bruce, an officer of the British East India Company, came across a variety of tea popular among the Singpho clan of Assam, India. He used this variety to develop the first tea garden in the Chauba area of Assam, and in 1840, the Assam Tea Company began production. This success was instrumental to the establishment of tea estates throughout India and in other British colonies. In 1848, the East India Company hired Robert Fortune, a plant hunter, to smuggle tea saplings and information about tea processing from China. Fortune was the superintendent of the hothouse department of the British Horticultural Society in Cheswick, London. He had visited China three times before this assignment; the first, in 1843, had been sponsored by the horticultural society, which was interested in acquiring important botanical treasures from China by exploiting the opportunity offered by the 1842 Treaty of Nanking after the First Opium War. Fortune managed to visit the interior of China (where foreigners were forbidden) and also gathered valuable information about the cultivation of important plants, successfully smuggling over 120 plant species into Britain. In the autumn of 1848, Fortune entered China and traveled for nearly three years while carefully collecting information related to tea cultivation and processing. He noted that black and green teas were made from the leaves of the same plant, Camellia sinensis, except that the former was “fermented” for a longer period. Eventually, Fortune succeeded in smuggling 20,000 saplings of Camellia sinensis to Calcutta, India, in Wardian cases.4 4. The Wardian case, a precursor to the modern terrarium, was a special type of sealed glass box made by British doctor Nathaniel Bagshaw Ward in 1829. The delicate plants within them could thrive for months. Plant hunter Joseph Hooker successfully used Wardian cases to bring some plants from the Antarctic to England. In 1933, Nathaniel Ward also succeeded in sending hundreds of small ornamental plants from England to Australia in these boxes. After two years, another voyage carried 56 | Colonial Agriculture He also brought trained artisans from China to India. These plants and artisans were transported from Calcutta to Darjeeling, Assam. At Darjeeling, a nursery was set up for the propagation of tea saplings at a large scale, supplying plantlets to all the tea gardens in India, Sri Lanka, and other British colonies. The British forced the poor tribal population of the Assam, Bengal, Bihar, and Orissa provinces out of their land, and they were sent to work in tea estates. Tamils from the southern province of India were also sent to work in the tea plantation of Sri Lanka. Tea plantations were modeled on the sugar colonies of the Caribbean, and thus the plight of the workers was in some ways similar to that of the slaves from Caribbean plantations. Samuel Davidson’s Sirocco tea dryer, the first tea-processing machine, was introduced in Sri Lanka in 1877, followed by John Walker’s tea-rolling machine in 1880. These machines were soon adopted by tea estates in India and other British colonies as well. As a result, British tea production increased greatly. By 1888, India became the number-one exporter of tea to Britain, sending the country 86 million pounds of tea. After India, Sri Lanka became prime ground for tea plantations. In the last decades of the nineteenth century, an outbreak of the fungal pathogen Hemilia vastatrix, a causal agent of rust, resulted in the destruction of the coffee plantations in Sri Lanka. The British owners of those estates quickly opted to plant tea instead, and a decade later, tea plantations covered nearly 400,000 acres of land in Sri Lanka. By 1927, Sri Lanka alone produced 100,000 tons per year. All this tea was for export. Within the British Empire, fermented black tea was produced, for which Assam, Ceylon, and Darjeeling tea are still famous. Black tea produced in India and Sri Lanka was considered of lesser quality than Chinese tea, but it was very cheap and easily became popular in Asian and African countries. In addition to India and Ceylon, British planters introduced tea plantations to fifty other countries. 3.6 The Story of Coffee Coffee is made from the roasted seeds of the coffee plant, a shrub belonging to the Rubiaceae family of flowering plants. There are over 120 species in the genus Coffea, and all are of tropical African origin. Only Coffea arabica and Coffea canephora are used for making coffee. Coffea arabica (figure 3.10) is preferred for its sweeter taste and is the source of 60–80 percent of the world’s coffee. It is an allotetraploid species that resulted from hybridization between the diploids Coffea canephora and Coffea eugenioides. In the Colonial Agriculture | 57 wild, coffee plants grow between thirty and forty feet tall and produce berries throughout the year. A coffee berry usually contains two seeds (a.k.a. beans). Coffee berries are nonclimacteric fruits, which ripen slowly on the plant itself (and unlike apples, bananas, mangoes, etc., their ripening cannot be induced after harvest by ethylene). Thus ripe berries, known as “cherries,” are picked every other week as they naturally ripen. To facilitate the manual picking of cherries, plants are pruned to a height of three to four feet. Pruning coffee plants is also essential to maximizing coffee production to maintain the correct balance of leaf to fruit, prevent overbearing, stimulate root growth, and effectively deter pests. Coffee is also a stimulative, and the secret of this elixir is the caffeine present in high quantities in its fruits and seeds. In its normal state, when our bodies are exhausted, there is an increase in adenosine molecules. The adenosine molecules bind to adenosine receptors in our brains, resulting in the transduction of sleep signals. The structure of caffeine is similar to that of adenosine, so when it reaches a weary brain, caffeine can also bind to the adenosine receptor and block adenosine molecules from accessing it, thus disrupting sleep signals. 58 | Colonial Agriculture 3.6.1 The History of Coffee Coffea arabica is native to Ethiopia. The people of Ethiopia first recognized the stimulative properties of coffee in the ninth century. According to legend, one day, a shepherd named Kaldi, who hailed from a small village in the highlands of Ethiopia, saw his goats dancing energetically after eating berries from a wild bush. Out of curiosity, he ate a few berries and felt refreshed. Kaldi took some berries back to the village to share, and the people there enjoyed them too. Hence the local custom of eating raw coffee berries began. There are records that coffee berries were often found in the pockets of slaves brought to the port of Mokha from the highlands of Ethiopia. Later, the people of Ethiopia started mixing ground berries with butter and herbs to make balls. The coffee we drink today was first brewed in Yemen in the thirteenth century. It became popular among Yemen’s clerics and Sufis, who routinely held religious and philosophical discussions late into the night; coffee rescued them from sleep and exhaustion. Gradually, coffee became popular, and coffeehouses opened up all over Arabia, where travelers, artists, poets, and common folks visited and had a chance to gossip and debate on a variety of topics, including politics. Often, governments shut down coffeehouses for fear of political unrest and revolution. Between the sixteenth and seventeenth centuries, coffeehouses were banned several times in many Arab countries, including Turkey, Mecca, and Egypt. But coffeehouses always opened again, and coffee became ingrained in Arab culture. Arabs developed many methods of processing coffee beans. Usually, these methods included drying coffee cherries to separate the beans. Dried coffee beans can be stored for many years. Larger and heavier beans are considered better. The taste and aroma develop during roasting, which determines the quality and price of the coffee. Dried coffee beans are dark green, but roasting them at a controlled temperature causes a slow transformation. First, they turn yellow, then light brown, while also popping up and doubling in size. After continued roasting, all the water inside them dries up, and the beans turn black like charcoal. The starch inside the beans first turns into sugar, and then sugar turns into caramel, at which point many aromatic compounds come out of the cells of the beans. Roasting coffee beans is an art, and a skilled roaster is a very important part of the coffee trade. 3.6.2 The Spread of Coffee out of Arabia Coffee was introduced to Europeans in the seventeenth century, when trade between the Ottoman Empire and Europe increased. In 1669, Turkish ambassador Suleiman Agha (Müteferrika Süleyman Ağa) arrived in the court of Louis XIV with many valuable gifts, Colonial Agriculture | 59 including coffee. The French subsequently became obsessed with the sophisticated etiquettes of the Ottoman Empire. In the company of Aga, the royal court and other elites of Parisian society indulged in drinking coffee. Aga held extravagant coffee ceremonies at his residence in Paris, where waiters dressed in Ottoman costumes served coffee to Parisian society women. Suleiman’s visit piqued French elites’ interest in Turquerie and Orientalism, which became fashionable. In the history of France, 1669 is thought of as the year of “Turkmenia.” A decade later, coffee reached Vienna, when Turkey was defeated in the Battle of 1683. After the victory, the Viennese seized the goods left behind by the Turkish soldiers, including several thousand sacks of coffee beans. The soldiers of Vienna didn’t know what it was and simply discarded it, but one man, Kolshitsky, snatched it up. Kolshitsky knew how to make coffee, and he opened the first coffeehouse in Vienna with the spoils. By the end of the seventeenth century, coffeehouses had become common in all the main cities of Europe. In London alone, by 1715, there were more than 2,000 coffeehouses. As in Arabia, the coffeehouses of Europe also became the bases of sociopolitical debates and were known as “penny universities.” 3.6.3 Coffee Plantations By the fifteenth century, demand for coffee had increased so much that the harvest of berries from the wild was not enough, and thus in Yemen, people began to plant coffee. Following Yemen’s lead, other Arab countries also started coffee plantations. Until the seventeenth century, coffee was cultivated only within North African and Arab countries. Arabs were very protective of their monopoly on the coffee trade. The cultivation of coffee and the processing of seeds was a mystery to the world outside of Arabia. Foreigners were not allowed to visit coffee farms, and only roasted coffee beans (incapable of producing new plants) were exported. Around 1600, Baba Budan, a Sufi who was on the Haj pilgrimage, successfully smuggled seven coffee seeds into India and started a small coffee nursery in Mysore. The early coffee plantations of South India used propagations of plants from Budan’s garden. In 1616, a Dutch spy also succeeded in stealing coffee beans from Arabia, and these were used by the Dutch East India Company as starters for coffee plantations in Java, Sumatra, Bali, Sri Lanka, Timur, and Suriname (Dutch Guiana). In 1706, a coffee plant from Java was brought to the botanic gardens of Amsterdam, and from there, its offspring reached Jardin de plantes in Paris. A clone of the Parisian plant was sent to the French colony Martinique, and then its offspring spread to the French colonies in the Caribbean, South America, and Africa. In 1728, a Portuguese officer from Dutch Guiana brought coffee seeds to Brazil, 60 | Colonial Agriculture which served as starters for the coffee plantations there. The Portuguese also introduced coffee to African countries and Indonesia, and the British established plantations in their Caribbean colonies, India, and Sri Lanka from Dutch stock. In summary, all European coffee plants came from the same Arabian mother plant. So the biodiversity within their coffee plantations was almost zero, which had devastating consequences. In the last decades of the nineteenth century, the fungal pathogen Haemilia vestatrix severely infected coffee plantations in Sri Lanka, India, Java, Sumatra, and Malaysia. As a result, rust disease destroyed the coffee plantations one by one. Later, in some of the coffee plantations, Coffea canephora (syn. Coffea robusta), which has a natural resistance to rust, was planted, but others were converted into tea plantations (as in the case of Sri Lanka, discussed earlier). European coffee plantations used the same model as tea or sugar plantations, and so their workers lived under the same conditions. European powers forcefully employed the poor native population in these plantations and used indentured laborers as needed. For example, in Sri Lanka, the Sinhalese population refused to work in the coffee farms, so British planters recruited 100,000 indentured Tamil workers from India to work the farms and tea plantations there. 3.7 The Heritage of Plantations In the twentieth century, most former European colonies became independent countries. In these countries, private, cooperative, or semigovernmental institutions manage plantations of sugarcane, tea, coffee, or other commercial crops. Though these plantations remain a significant source of revenue and contribute significantly to the national GDP of many countries, their workers still often operate under abject conditions. References Johannessen, C. L., & Sorenson, J. L. (2009). World trade and biological exchanges before 1492. iUniverse. (↵ Return)

Only give responses with information found in the text below. Limit your response to 200 words or less. Focus on historical significance that could be linked to current practices. Keep in the style of formal writing for a college institution. What were the negatives of having such low biodiversity for the coffee plant? Context: tall bushes to promote branching and the production of new leaves, as well as to facilitate plucking them. Various processing methods are used to attain different levels of oxidation and produce certain kinds of tea, such as black, white, oolong, green, and pu’erh. Basic processing includes plucking, withering (to wilt and soften the leaves), rolling (to shape the leaves and slow drying), oxidizing, and drying. However, depending on the tea type, some steps are repeated or omitted. For example, green tea is made by withering and rolling leaves at a low heat, and oxidation is skipped; for oolong, rolling and oxidizing are performed repeatedly; and for black, extensive oxidation (fermentation) is employed. 3.5.1 The Discovery of Tea Tea was discovered in 2700 BCE by the ancient Chinese emperor Shen Nung, who had a keen interest in herbal medicine and introduced the practice of drinking boiled water to prevent stomach ailments. According to legend, once, when the emperor camped in a forest during one of his excursions, his servants set up a pot of boiling water under a tree. A fragrance attracted his attention, and he found that a few dry leaves from the tree had Colonial Agriculture | 53 fallen accidentally into the boiling pot and changed the color of the water; this was the source of the aroma. He took a few sips of that water and noticed its stimulative effect instantly. The emperor experimented with the leaves of that tree, now called Camellia sinensis, and thus the drink “cha” came into existence. Initially, it was used as a tonic, but it became a popular beverage around 350 BCE. The historian Lu Yu of the Tang dynasty (618–907 CE) has written a poetry book on tea called Cha jing (The Classic of Tea) that contains a detailed description of how to cultivate, process, and brew tea. Tea spread to Japan and Korea in the seventh century thanks to Buddhist monks, and drinking it became an essential cultural ritual. Formal tea ceremonies soon began. However, tea reached other countries only after the sixteenth century. In 1557, the Portuguese established their first trading center in Macau, and the Dutch soon followed suit. In 1610, some Dutch traders in Macau took tea back to the Dutch royal family as a gift. The royal family took an immediate liking to it. When the Dutch princess Catherine of Braganza married King Charles II of England around 1650, she introduced tea to England. Tea passed from the royal family to the nobles, but for an extended period, it remained unknown and unaffordable to common folks in Europe. The supply of tea in Europe was scant and very costly: one pound of tea was equal to nine months’ wages for a British laborer. As European trade with China increased, more tea reached Europe, and consumption of tea increased proportionally. For example, in 1680, Britain imported a hundred pounds of tea; however, in 1700, it brought in a million. The British government allowed the British East India Company to monopolize the trade, and by 1785, the company was buying 15 million pounds of tea from China annually and selling it worldwide. Eventually, in the early eighteenth century, tea reached the homes of British commoners. 3.5.2 Tea and the “Opium War” China was self-sufficient; its people wanted nothing from Europe in exchange for tea. But in Europe, the demand for tea increased rapidly in the mid-eighteenth century. Large quantities were being purchased, and Europeans had to pay in silver and gold. The East India Company was buying so much of it that it caused a crisis for the mercantilist British economy. The company came up with a plan to buy tea in exchange for opium instead of gold and silver. Although opium was banned within China, it was in demand and sold at very high prices on the black market. After the Battle of Plassey in 1757, several northern provinces in India came under the control of the East India Company, and the company began cultivating poppy in Bengal, Bihar, Orissa, and eastern Uttar Pradesh. Such cultivation was compulsory, and the 54 | Colonial Agriculture company also banned farmers from growing grain and built opium factories in Patna and Banaras. The opium was then transported to Calcutta for auction before British ships carried it to the Chinese border. The East India Company also helped set up an extensive network of opium smugglers in China, who then transported opium domestically and sold it on the black market. After the successful establishment of this smuggling network, British ships bought tea on credit at the port of Canton (now Guangzhou), China, and later paid for it with opium in Calcutta (now Kolkata). The company not only acquired the tea that was so in demand but also started making huge profits from selling opium. This mixed business of opium and tea began to strengthen the British economy and made it easier for the British to become front-runners among the European powers. By the 1830s, British traders were selling 1,400 tons of opium to China every year, and as a result, a large number of Chinese became opium addicts. The Chinese government began a crackdown on smugglers and further tightened the laws related to opium, and in 1838, it imposed death sentences on opium smugglers. Furthermore, despite immense pressure from the East India Company to allow the open trading of opium, the Chinese emperor would not capitulate. However, that did not curb his subjects’ addiction and the growing demand for opium. In 1839, by order of the Chinese emperor, a British ship was detained in the port of Canton, and the opium therein was destroyed. The British government asked the Chinese emperor to apologize and demanded compensation; he refused. British retaliated by attacking a number of Chinese ports and coastal cities. China could not compete with Britain’s state-of- the-art weapons, and defeated, China accepted the terms of the Treaty of Nanjing in 1842 and the Treaty of Bog in 1843, which opened the ports of Canton, Fujian, and Shanghai, among others, to British merchants and other Europeans. In 1856, another small war broke out between China and Britain, which ended with a treaty that made the sale of opium legal and allowed Christian missionaries to operate in China. But the tension between China and Europe remained. In 1859, the British and French seized Beijing and burned the royal Summer Palace. The subsequent Beijing Convention of 1860 ended China’s sovereignty, and the British gained a monopoly on the tea trade. 3.5.3 The Co-option of Tea and the Establishment of Plantations in European Colonies Unlike the British, the Dutch, Portuguese, and French had less success in the tea trade. To overcome British domination, the Portuguese planned to develop tea gardens outside China. Camellia is native to China, and it was not found in any other country. There was Colonial Agriculture | 55 a law against taking these plants out of the country, and the method for processing tea was also a trade secret. In the mid-eighteenth century, many Europeans smuggled the seeds and plants from China, but they were unable to grow them. Then, in 1750, the Portuguese smuggled the Camellia plants and some trained specialists out of China and succeeded in establishing tea gardens in the mountainous regions of the Azores Islands, which have a climate favorable for tea cultivation. With the help of Chinese laborers and experts, black and green tea were successfully produced in the Portuguese tea plantations. Soon, Portugal and its colonies no longer needed to import tea at all. As the owners of the first tea plantations outside China, the Portuguese remained vigilant in protecting their monopoly. It was some time before other European powers gained the ability to grow and process tea themselves. In the early nineteenth century, the British began exploring the idea of planting tea saplings in India. In 1824, Robert Bruce, an officer of the British East India Company, came across a variety of tea popular among the Singpho clan of Assam, India. He used this variety to develop the first tea garden in the Chauba area of Assam, and in 1840, the Assam Tea Company began production. This success was instrumental to the establishment of tea estates throughout India and in other British colonies. In 1848, the East India Company hired Robert Fortune, a plant hunter, to smuggle tea saplings and information about tea processing from China. Fortune was the superintendent of the hothouse department of the British Horticultural Society in Cheswick, London. He had visited China three times before this assignment; the first, in 1843, had been sponsored by the horticultural society, which was interested in acquiring important botanical treasures from China by exploiting the opportunity offered by the 1842 Treaty of Nanking after the First Opium War. Fortune managed to visit the interior of China (where foreigners were forbidden) and also gathered valuable information about the cultivation of important plants, successfully smuggling over 120 plant species into Britain. In the autumn of 1848, Fortune entered China and traveled for nearly three years while carefully collecting information related to tea cultivation and processing. He noted that black and green teas were made from the leaves of the same plant, Camellia sinensis, except that the former was “fermented” for a longer period. Eventually, Fortune succeeded in smuggling 20,000 saplings of Camellia sinensis to Calcutta, India, in Wardian cases.4 4. The Wardian case, a precursor to the modern terrarium, was a special type of sealed glass box made by British doctor Nathaniel Bagshaw Ward in 1829. The delicate plants within them could thrive for months. Plant hunter Joseph Hooker successfully used Wardian cases to bring some plants from the Antarctic to England. In 1933, Nathaniel Ward also succeeded in sending hundreds of small ornamental plants from England to Australia in these boxes. After two years, another voyage carried 56 | Colonial Agriculture He also brought trained artisans from China to India. These plants and artisans were transported from Calcutta to Darjeeling, Assam. At Darjeeling, a nursery was set up for the propagation of tea saplings at a large scale, supplying plantlets to all the tea gardens in India, Sri Lanka, and other British colonies. The British forced the poor tribal population of the Assam, Bengal, Bihar, and Orissa provinces out of their land, and they were sent to work in tea estates. Tamils from the southern province of India were also sent to work in the tea plantation of Sri Lanka. Tea plantations were modeled on the sugar colonies of the Caribbean, and thus the plight of the workers was in some ways similar to that of the slaves from Caribbean plantations. Samuel Davidson’s Sirocco tea dryer, the first tea-processing machine, was introduced in Sri Lanka in 1877, followed by John Walker’s tea-rolling machine in 1880. These machines were soon adopted by tea estates in India and other British colonies as well. As a result, British tea production increased greatly. By 1888, India became the number-one exporter of tea to Britain, sending the country 86 million pounds of tea. After India, Sri Lanka became prime ground for tea plantations. In the last decades of the nineteenth century, an outbreak of the fungal pathogen Hemilia vastatrix, a causal agent of rust, resulted in the destruction of the coffee plantations in Sri Lanka. The British owners of those estates quickly opted to plant tea instead, and a decade later, tea plantations covered nearly 400,000 acres of land in Sri Lanka. By 1927, Sri Lanka alone produced 100,000 tons per year. All this tea was for export. Within the British Empire, fermented black tea was produced, for which Assam, Ceylon, and Darjeeling tea are still famous. Black tea produced in India and Sri Lanka was considered of lesser quality than Chinese tea, but it was very cheap and easily became popular in Asian and African countries. In addition to India and Ceylon, British planters introduced tea plantations to fifty other countries. 3.6 The Story of Coffee Coffee is made from the roasted seeds of the coffee plant, a shrub belonging to the Rubiaceae family of flowering plants. There are over 120 species in the genus Coffea, and all are of tropical African origin. Only Coffea arabica and Coffea canephora are used for making coffee. Coffea arabica (figure 3.10) is preferred for its sweeter taste and is the source of 60–80 percent of the world’s coffee. It is an allotetraploid species that resulted from hybridization between the diploids Coffea canephora and Coffea eugenioides. In the Colonial Agriculture | 57 wild, coffee plants grow between thirty and forty feet tall and produce berries throughout the year. A coffee berry usually contains two seeds (a.k.a. beans). Coffee berries are nonclimacteric fruits, which ripen slowly on the plant itself (and unlike apples, bananas, mangoes, etc., their ripening cannot be induced after harvest by ethylene). Thus ripe berries, known as “cherries,” are picked every other week as they naturally ripen. To facilitate the manual picking of cherries, plants are pruned to a height of three to four feet. Pruning coffee plants is also essential to maximizing coffee production to maintain the correct balance of leaf to fruit, prevent overbearing, stimulate root growth, and effectively deter pests. Coffee is also a stimulative, and the secret of this elixir is the caffeine present in high quantities in its fruits and seeds. In its normal state, when our bodies are exhausted, there is an increase in adenosine molecules. The adenosine molecules bind to adenosine receptors in our brains, resulting in the transduction of sleep signals. The structure of caffeine is similar to that of adenosine, so when it reaches a weary brain, caffeine can also bind to the adenosine receptor and block adenosine molecules from accessing it, thus disrupting sleep signals. 58 | Colonial Agriculture 3.6.1 The History of Coffee Coffea arabica is native to Ethiopia. The people of Ethiopia first recognized the stimulative properties of coffee in the ninth century. According to legend, one day, a shepherd named Kaldi, who hailed from a small village in the highlands of Ethiopia, saw his goats dancing energetically after eating berries from a wild bush. Out of curiosity, he ate a few berries and felt refreshed. Kaldi took some berries back to the village to share, and the people there enjoyed them too. Hence the local custom of eating raw coffee berries began. There are records that coffee berries were often found in the pockets of slaves brought to the port of Mokha from the highlands of Ethiopia. Later, the people of Ethiopia started mixing ground berries with butter and herbs to make balls. The coffee we drink today was first brewed in Yemen in the thirteenth century. It became popular among Yemen’s clerics and Sufis, who routinely held religious and philosophical discussions late into the night; coffee rescued them from sleep and exhaustion. Gradually, coffee became popular, and coffeehouses opened up all over Arabia, where travelers, artists, poets, and common folks visited and had a chance to gossip and debate on a variety of topics, including politics. Often, governments shut down coffeehouses for fear of political unrest and revolution. Between the sixteenth and seventeenth centuries, coffeehouses were banned several times in many Arab countries, including Turkey, Mecca, and Egypt. But coffeehouses always opened again, and coffee became ingrained in Arab culture. Arabs developed many methods of processing coffee beans. Usually, these methods included drying coffee cherries to separate the beans. Dried coffee beans can be stored for many years. Larger and heavier beans are considered better. The taste and aroma develop during roasting, which determines the quality and price of the coffee. Dried coffee beans are dark green, but roasting them at a controlled temperature causes a slow transformation. First, they turn yellow, then light brown, while also popping up and doubling in size. After continued roasting, all the water inside them dries up, and the beans turn black like charcoal. The starch inside the beans first turns into sugar, and then sugar turns into caramel, at which point many aromatic compounds come out of the cells of the beans. Roasting coffee beans is an art, and a skilled roaster is a very important part of the coffee trade. 3.6.2 The Spread of Coffee out of Arabia Coffee was introduced to Europeans in the seventeenth century, when trade between the Ottoman Empire and Europe increased. In 1669, Turkish ambassador Suleiman Agha (Müteferrika Süleyman Ağa) arrived in the court of Louis XIV with many valuable gifts, Colonial Agriculture | 59 including coffee. The French subsequently became obsessed with the sophisticated etiquettes of the Ottoman Empire. In the company of Aga, the royal court and other elites of Parisian society indulged in drinking coffee. Aga held extravagant coffee ceremonies at his residence in Paris, where waiters dressed in Ottoman costumes served coffee to Parisian society women. Suleiman’s visit piqued French elites’ interest in Turquerie and Orientalism, which became fashionable. In the history of France, 1669 is thought of as the year of “Turkmenia.” A decade later, coffee reached Vienna, when Turkey was defeated in the Battle of 1683. After the victory, the Viennese seized the goods left behind by the Turkish soldiers, including several thousand sacks of coffee beans. The soldiers of Vienna didn’t know what it was and simply discarded it, but one man, Kolshitsky, snatched it up. Kolshitsky knew how to make coffee, and he opened the first coffeehouse in Vienna with the spoils. By the end of the seventeenth century, coffeehouses had become common in all the main cities of Europe. In London alone, by 1715, there were more than 2,000 coffeehouses. As in Arabia, the coffeehouses of Europe also became the bases of sociopolitical debates and were known as “penny universities.” 3.6.3 Coffee Plantations By the fifteenth century, demand for coffee had increased so much that the harvest of berries from the wild was not enough, and thus in Yemen, people began to plant coffee. Following Yemen’s lead, other Arab countries also started coffee plantations. Until the seventeenth century, coffee was cultivated only within North African and Arab countries. Arabs were very protective of their monopoly on the coffee trade. The cultivation of coffee and the processing of seeds was a mystery to the world outside of Arabia. Foreigners were not allowed to visit coffee farms, and only roasted coffee beans (incapable of producing new plants) were exported. Around 1600, Baba Budan, a Sufi who was on the Haj pilgrimage, successfully smuggled seven coffee seeds into India and started a small coffee nursery in Mysore. The early coffee plantations of South India used propagations of plants from Budan’s garden. In 1616, a Dutch spy also succeeded in stealing coffee beans from Arabia, and these were used by the Dutch East India Company as starters for coffee plantations in Java, Sumatra, Bali, Sri Lanka, Timur, and Suriname (Dutch Guiana). In 1706, a coffee plant from Java was brought to the botanic gardens of Amsterdam, and from there, its offspring reached Jardin de plantes in Paris. A clone of the Parisian plant was sent to the French colony Martinique, and then its offspring spread to the French colonies in the Caribbean, South America, and Africa. In 1728, a Portuguese officer from Dutch Guiana brought coffee seeds to Brazil, 60 | Colonial Agriculture which served as starters for the coffee plantations there. The Portuguese also introduced coffee to African countries and Indonesia, and the British established plantations in their Caribbean colonies, India, and Sri Lanka from Dutch stock. In summary, all European coffee plants came from the same Arabian mother plant. So the biodiversity within their coffee plantations was almost zero, which had devastating consequences. In the last decades of the nineteenth century, the fungal pathogen Haemilia vestatrix severely infected coffee plantations in Sri Lanka, India, Java, Sumatra, and Malaysia. As a result, rust disease destroyed the coffee plantations one by one. Later, in some of the coffee plantations, Coffea canephora (syn. Coffea robusta), which has a natural resistance to rust, was planted, but others were converted into tea plantations (as in the case of Sri Lanka, discussed earlier). European coffee plantations used the same model as tea or sugar plantations, and so their workers lived under the same conditions. European powers forcefully employed the poor native population in these plantations and used indentured laborers as needed. For example, in Sri Lanka, the Sinhalese population refused to work in the coffee farms, so British planters recruited 100,000 indentured Tamil workers from India to work the farms and tea plantations there. 3.7 The Heritage of Plantations In the twentieth century, most former European colonies became independent countries. In these countries, private, cooperative, or semigovernmental institutions manage plantations of sugarcane, tea, coffee, or other commercial crops. Though these plantations remain a significant source of revenue and contribute significantly to the national GDP of many countries, their workers still often operate under abject conditions. References Johannessen, C. L., & Sorenson, J. L. (2009). World trade and biological exchanges before 1492. iUniverse. (↵ Return)

Provide responses in clear, concise and simple manner. The target audience has no knowledge of the subject and are not experts. You response should only rely on the provided context.

In what ways is Biden trying to improve the life of the average American?

Biden Portrays Next Phase of Economic Agenda as Middle-Class Lifeline The president used his State of the Union speech to pitch tax increases for the rich, along with plans to cut costs and protect consumers. President Biden used his State of the Union speech on Thursday to remind Americans of his efforts to steer the nation’s economy out of a pandemic recession, and to lay the groundwork for a second term focused on making the economy more equitable by raising taxes on companies and the wealthy while taking steps to reduce costs for the middle class. Mr. Biden offered a blitz of policies squarely targeting the middle class, including efforts to make housing more affordable for first-time home buyers. The president used his speech to try and differentiate his economic proposals with those supported by Republicans, including former President Donald J. Trump. Those proposals have largely centered on cutting taxes, rolling back the Biden administration’s investments in clean energy and gutting the Internal Revenue Service. Many of Mr. Biden’s policy proposals would require acts of Congress and hinge on Democrats winning control of the House and the Senate. However, the president also unveiled plans to direct federal agencies to use their powers to reduce costs for big-ticket items like housing at a time when the lingering effects of inflation continue to weigh on economic sentiment. From taxes and housing to inflation and consumer protection, Mr. Biden had his eye on pocketbook issues. Raising Taxes on the Rich Many of the tax cuts that Mr. Trump signed into law in 2017 are set to expire next year, making tax policy among the most critical issues on the ballot this year. On Thursday night, Mr. Biden built upon many of the tax proposals that he has been promoting for the last three years, calling for big corporations and the wealthiest Americans to pay more. He proposed raising a new corporate minimum tax to 21 percent from 15 percent and proposed a new 25 percent minimum tax rate for billionaires, which he said would raise $500 billion over a decade. Criticizing the cost of the 2017 tax cuts, Mr. Biden asked, “Do you really think the wealthy and big corporations need another $2 trillion in tax breaks?” Help for the Housing Market High interest rates have made housing unaffordable for many Americans, and Mr. Biden called for a mix of measures to help ease those costs. That included tax credits and mortgage assistance for first-time home buyers and new incentives to encourage the construction and renovation of affordable housing. Mr. Biden called on Congress to make certain first-time buyers eligible for a $10,000 credit, along with making some “first generation” home buyers eligible for up to $25,000 toward a down payment. The president also unveiled new grants and incentives to encourage the construction of affordable housing. He also said the Consumer Financial Protection Bureau would be pursuing new rules to address “anticompetitive” closing costs that lenders impose on buyers and sellers, and called for more scrutiny of landlords who collude to raise rents and sneak hidden fees into rental agreements. Our politics reporters. Times journalists are not allowed to endorse or campaign for candidates or political causes. That includes participating in rallies and donating money to a candidate or cause. Learn more about our process. Protecting Consumers From “Shrinkflation” There is only so much that a president can do to tame rapid inflation, but Mr. Biden used his remarks to lean into his favorite new boogeyman: shrinkflation. “Same size bag, put fewer chips in it,” Mr. Biden said. He called on lawmakers to pass legislation to put an end to the corporate practice of reducing the size of products without reducing their price tag. The president also touted his efforts to cut credit card late charges and “junk” fees and to eliminate surprise fees for online ticket sales, and he claimed to be saving Americans billions of dollars from various forms of price gouging. Building and Buying American One of the mysteries that consume Mr. Biden’s advisers is why he does not get sufficient credit for the major pieces of legislation that have been enacted during the last three years. The president blitzed through those accomplishments, reminding his audience of the construction of new roads and bridges and investments in the development of microchips and clean energy manufacturing. Veering off script, Mr. Biden ribbed Republicans for voting against some of those policies while reaping the benefits of the investments in their states. Tackling China As president, Mr. Biden has prioritized stabilizing America’s economic relationship with China while also trying to reduce the United States’ reliance on Chinese products. Mr. Biden took aim at Mr. Trump, saying that while the former president portrayed himself as tough on China, the Biden administration’s policies were having a bigger impact on shrinking the bilateral trade deficit and powering U.S. economic growth. The president added that his administration had been pushing back against China’s unfair trade practices and keeping exports of sensitive American technology away from the Chinese military. He said that Republicans who claim that the U.S. is falling behind China were wrong. “America is rising,” Mr. Biden said. “We have the best economy in the world.”

Provide responses in clear, concise and simple manner. The target audience has no knowledge of the subject and are not experts. You response should only rely on the provided context. In what ways is Biden trying to improve the life of the average American? Biden Portrays Next Phase of Economic Agenda as Middle-Class Lifeline The president used his State of the Union speech to pitch tax increases for the rich, along with plans to cut costs and protect consumers. President Biden used his State of the Union speech on Thursday to remind Americans of his efforts to steer the nation’s economy out of a pandemic recession, and to lay the groundwork for a second term focused on making the economy more equitable by raising taxes on companies and the wealthy while taking steps to reduce costs for the middle class. Mr. Biden offered a blitz of policies squarely targeting the middle class, including efforts to make housing more affordable for first-time home buyers. The president used his speech to try and differentiate his economic proposals with those supported by Republicans, including former President Donald J. Trump. Those proposals have largely centered on cutting taxes, rolling back the Biden administration’s investments in clean energy and gutting the Internal Revenue Service. Many of Mr. Biden’s policy proposals would require acts of Congress and hinge on Democrats winning control of the House and the Senate. However, the president also unveiled plans to direct federal agencies to use their powers to reduce costs for big-ticket items like housing at a time when the lingering effects of inflation continue to weigh on economic sentiment. From taxes and housing to inflation and consumer protection, Mr. Biden had his eye on pocketbook issues. Raising Taxes on the Rich Many of the tax cuts that Mr. Trump signed into law in 2017 are set to expire next year, making tax policy among the most critical issues on the ballot this year. On Thursday night, Mr. Biden built upon many of the tax proposals that he has been promoting for the last three years, calling for big corporations and the wealthiest Americans to pay more. He proposed raising a new corporate minimum tax to 21 percent from 15 percent and proposed a new 25 percent minimum tax rate for billionaires, which he said would raise $500 billion over a decade. Criticizing the cost of the 2017 tax cuts, Mr. Biden asked, “Do you really think the wealthy and big corporations need another $2 trillion in tax breaks?” Help for the Housing Market High interest rates have made housing unaffordable for many Americans, and Mr. Biden called for a mix of measures to help ease those costs. That included tax credits and mortgage assistance for first-time home buyers and new incentives to encourage the construction and renovation of affordable housing. Mr. Biden called on Congress to make certain first-time buyers eligible for a $10,000 credit, along with making some “first generation” home buyers eligible for up to $25,000 toward a down payment. The president also unveiled new grants and incentives to encourage the construction of affordable housing. He also said the Consumer Financial Protection Bureau would be pursuing new rules to address “anticompetitive” closing costs that lenders impose on buyers and sellers, and called for more scrutiny of landlords who collude to raise rents and sneak hidden fees into rental agreements. Our politics reporters. Times journalists are not allowed to endorse or campaign for candidates or political causes. That includes participating in rallies and donating money to a candidate or cause. Learn more about our process. Protecting Consumers From “Shrinkflation” There is only so much that a president can do to tame rapid inflation, but Mr. Biden used his remarks to lean into his favorite new boogeyman: shrinkflation. “Same size bag, put fewer chips in it,” Mr. Biden said. He called on lawmakers to pass legislation to put an end to the corporate practice of reducing the size of products without reducing their price tag. The president also touted his efforts to cut credit card late charges and “junk” fees and to eliminate surprise fees for online ticket sales, and he claimed to be saving Americans billions of dollars from various forms of price gouging. Building and Buying American One of the mysteries that consume Mr. Biden’s advisers is why he does not get sufficient credit for the major pieces of legislation that have been enacted during the last three years. The president blitzed through those accomplishments, reminding his audience of the construction of new roads and bridges and investments in the development of microchips and clean energy manufacturing. Veering off script, Mr. Biden ribbed Republicans for voting against some of those policies while reaping the benefits of the investments in their states. Tackling China As president, Mr. Biden has prioritized stabilizing America’s economic relationship with China while also trying to reduce the United States’ reliance on Chinese products. Mr. Biden took aim at Mr. Trump, saying that while the former president portrayed himself as tough on China, the Biden administration’s policies were having a bigger impact on shrinking the bilateral trade deficit and powering U.S. economic growth. The president added that his administration had been pushing back against China’s unfair trade practices and keeping exports of sensitive American technology away from the Chinese military. He said that Republicans who claim that the U.S. is falling behind China were wrong. “America is rising,” Mr. Biden said. “We have the best economy in the world.”

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

How does a 10-week diet rich in fermented foods regulate the immune system? What are the implications of regulating the immune system for inflammation? Please give examples.

Fermented-food diet increases microbiome diversity, decreases inflammatory proteins, study finds Stanford researchers discover that a 10-week diet high in fermented foods boosts microbiome diversity and improves immune responses. July 12, 2021 - By Janelle Weaver A diet rich in fermented foods enhances the diversity of gut microbes and decreases molecular signs of inflammation, according to researchers at the Stanford School of Medicine. In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system. Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. “This is a stunning finding,” said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. “It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults.” In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress. “Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. “This finding was consistent across all participants in the study who were assigned to the higher fermented food group.” Justin Sonnenburg Justin Sonnenburg Microbe diversity stable in fiber-rich diet By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. “We expected high fiber to have a more universally beneficial effect and increase microbiota diversity,” said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. “The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity.” The study published online July 12 in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco. A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes. “We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases,” Gardner said. The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease. Erica Sonnenburg Erica Sonnenburg The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose. The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers’ previous reports of a general resilience of the human microbiome over short time periods.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. How does a 10-week diet rich in fermented foods regulate the immune system? What are the implications of regulating the immune system for inflammation? Please give examples. Fermented-food diet increases microbiome diversity, decreases inflammatory proteins, study finds Stanford researchers discover that a 10-week diet high in fermented foods boosts microbiome diversity and improves immune responses. July 12, 2021 - By Janelle Weaver A diet rich in fermented foods enhances the diversity of gut microbes and decreases molecular signs of inflammation, according to researchers at the Stanford School of Medicine. In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system. Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. “This is a stunning finding,” said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. “It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults.” In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress. “Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. “This finding was consistent across all participants in the study who were assigned to the higher fermented food group.” Justin Sonnenburg Justin Sonnenburg Microbe diversity stable in fiber-rich diet By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. “We expected high fiber to have a more universally beneficial effect and increase microbiota diversity,” said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. “The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity.” The study published online July 12 in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco. A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes. “We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases,” Gardner said. The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease. Erica Sonnenburg Erica Sonnenburg The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose. The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers’ previous reports of a general resilience of the human microbiome over short time periods. https://med.stanford.edu/news/all-news/2021/07/fermented-food-diet-increases-microbiome-diversity-lowers-inflammation

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

I need to know what is effective primary and secondary line therapy. Are there any specific genes to look out for? What are some targeted antibodies? Make your response in bullet points and be sure to keep it less than 400 words.

Ovarian cancer often progresses significantly before a patient is diagnosed. This is because the symptoms of ovarian cancer can be easily confused with less life-threatening digestive issues such as bloating, constipation, and gas. Roughly only 20 percent of ovarian cancers are detected before it spreads beyond the ovaries. Unfortunately, to date, no screening tests have been demonstrated to improve early detection and outcomes of people with ovarian cancer. The most prominent risk factor for this disease is a family history that includes breast or ovarian cancer. People who test positive for the inherited mutations in the BRCA1 or BRCA2 genes are at significantly greater risk—45% to 65% risk of developing breast cancer and 10% to 20% risk of developing ovarian cancer by age 70. Globally, ovarian cancer is diagnosed in an estimated 300,000 people each year, and causes roughly 180,000 deaths. In 2023, ovarian cancer will be diagnosed in approximately 20,000 people and cause about 13,000 deaths in the United States. While significant advances have been made in surgical and chemo-based treatments for ovarian cancer, the survival rates have only modestly improved. The poor survival in advanced ovarian cancer is due both to late diagnosis as well as to the lack of effective second-line therapy for patients who relapse. Many people affected by advanced ovarian cancer respond to chemotherapy, but effects are not typically long-lasting. The clinical course of ovarian cancer patients is marked by periods of remission and relapse of sequentially shortening duration until chemotherapy resistance develops. More than 80% of ovarian cancer patients experience recurrent disease, and more than 50% of these patients die from the disease in less than five years post-diagnosis. There is an urgent need for new treatments for advanced stage, recurring ovarian cancer. Subscribe To Email Alerts Ovarian Cancer Treatment Options First-line treatment for ovarian cancer includes surgery followed by a chemotherapy regimen combining a platinum-based (usually carboplatin) and a taxane-based (usually paclitaxel) treatment. This course of treatment leads to a complete response in approximately 80% of patients. A complete response means no visible evidence of disease on imaging scans and normal blood tests. After completion of upfront chemotherapy, patients may be eligible to receive maintenance therapy with a new class of drugs called PARP inhibitors, which have been demonstrated to significantly delay and possibly even prevent disease relapse in some patients, particularly patients whose tumor carry mutations in BRCA1 and BRCA2 genes. Patients who initially respond to treatment but then relapse after a period of six months or more may undergo the same therapy. Patients who progress during first-line treatment or who relapse within six months following successful first-line treatment are considered refractory or resistant to platinum-based treatments. For these patients, there are several chemotherapeutic options; however, each has shown only marginal benefit. Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently three FDA-approved immunotherapy options for ovarian cancer. Targeted Antibodies Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for patients with newly-diagnosed and with relapsed ovarian cancer Mirvetuximab soravtansine (ElahereTM): an antibody-drug conjugate that targets the folate receptor apathway and delivers toxic drugs to tumors; approved for subsets of patients with advanced ovarian cancer Immunomodulators Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced ovarian cancer that has DNA mismatch repair deficiency (dMMR) Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced ovarian cancer that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. I need to know what is effective primary and secondary line therapy. Are there any specific genes to look out for? What are some targeted antibodies? Make your response in bullet points and be sure to keep it less than 400 words. Ovarian cancer often progresses significantly before a patient is diagnosed. This is because the symptoms of ovarian cancer can be easily confused with less life-threatening digestive issues such as bloating, constipation, and gas. Roughly only 20 percent of ovarian cancers are detected before it spreads beyond the ovaries. Unfortunately, to date, no screening tests have been demonstrated to improve early detection and outcomes of people with ovarian cancer. The most prominent risk factor for this disease is a family history that includes breast or ovarian cancer. People who test positive for the inherited mutations in the BRCA1 or BRCA2 genes are at significantly greater risk—45% to 65% risk of developing breast cancer and 10% to 20% risk of developing ovarian cancer by age 70. Globally, ovarian cancer is diagnosed in an estimated 300,000 people each year, and causes roughly 180,000 deaths. In 2023, ovarian cancer will be diagnosed in approximately 20,000 people and cause about 13,000 deaths in the United States. While significant advances have been made in surgical and chemo-based treatments for ovarian cancer, the survival rates have only modestly improved. The poor survival in advanced ovarian cancer is due both to late diagnosis as well as to the lack of effective second-line therapy for patients who relapse. Many people affected by advanced ovarian cancer respond to chemotherapy, but effects are not typically long-lasting. The clinical course of ovarian cancer patients is marked by periods of remission and relapse of sequentially shortening duration until chemotherapy resistance develops. More than 80% of ovarian cancer patients experience recurrent disease, and more than 50% of these patients die from the disease in less than five years post-diagnosis. There is an urgent need for new treatments for advanced stage, recurring ovarian cancer. Subscribe To Email Alerts Ovarian Cancer Treatment Options First-line treatment for ovarian cancer includes surgery followed by a chemotherapy regimen combining a platinum-based (usually carboplatin) and a taxane-based (usually paclitaxel) treatment. This course of treatment leads to a complete response in approximately 80% of patients. A complete response means no visible evidence of disease on imaging scans and normal blood tests. After completion of upfront chemotherapy, patients may be eligible to receive maintenance therapy with a new class of drugs called PARP inhibitors, which have been demonstrated to significantly delay and possibly even prevent disease relapse in some patients, particularly patients whose tumor carry mutations in BRCA1 and BRCA2 genes. Patients who initially respond to treatment but then relapse after a period of six months or more may undergo the same therapy. Patients who progress during first-line treatment or who relapse within six months following successful first-line treatment are considered refractory or resistant to platinum-based treatments. For these patients, there are several chemotherapeutic options; however, each has shown only marginal benefit. Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently three FDA-approved immunotherapy options for ovarian cancer. Targeted Antibodies Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for patients with newly-diagnosed and with relapsed ovarian cancer Mirvetuximab soravtansine (ElahereTM): an antibody-drug conjugate that targets the folate receptor apathway and delivers toxic drugs to tumors; approved for subsets of patients with advanced ovarian cancer Immunomodulators Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced ovarian cancer that has DNA mismatch repair deficiency (dMMR) Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced ovarian cancer that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H) https://www.cancerresearch.org/cancer-types/ovarian-cancer

Use only the information provided below to formulate your answer, and format the answer using bullet points where appropriate.

Compare the financial facts and figures of families with children to families without children.

Many families are in financial distress, and families with children are especially vulnerable. Thirty-eight percent of families with children under age 18 living at home are struggling to get by, compared with 33 percent of families without children at home (figure 1). Financial distress can arise from a range of factors, from a specific hardship— 28 percent of families with children experienced a financial hardship in the past year, compared with 23 percent of families without children—to a simple lack of sufficient income. Twenty-four percent of families with children spent more than their income last year, compared with 19 percent of families without children. Raising children is expensive, and the costs have been rising over time. According to the USDA, the typical two-parent family can expect to spend between $13,000 and $15,000 per child per year for children born in 2013, meaning that the average cost of raising a child is expected to be $245,000 over 18 years (Lino 2014). A family with two children can expect to spend almost half its income on its children each year. Not only are children expensive, but families with children tend to have lower incomes than families without children. In 2014, the median income for families with children was about $62,000, compared with about $68,000 for families without children (figure 2). While men’s earnings increase after fatherhood, women with children have lower average earnings than women without children. These differences hold true even when looking only at working people and when controlling for years of experience and other attributes (Budig 2014; Pal and Waldfogel 2014). As single-mother families become more common, the “fatherhood bump” no longer offsets the “motherhood penalty” for many families. Public benefits are not enough to offset the increased cost of having children. Available federal programs such as Medicaid, SNAP (the Supplemental Nutrition Assistance Program), and TANF, as well as tax incentives such as the EITC (the earned income tax credit) lift millions of families with children out of poverty (Sherman, Trisi, and Parrott 2013), but they are often not enough to lift families out of financial distress. Many of the programs that focus on families with children are shrinking, despite the increased costs of having children. Total federal spending on children, currently 10 percent of the federal budget, is projected to decline to less than 8 percent in 2025, while adult Social Security, Medicare, and Medicaid spending is projected to increase to 49 percent (Isaacs et al. 2015). Some of the differences between families with and without children at home may be attributable to older families whose children are no longer at home or younger families who do not have children yet, rather than adults of childrearing age without children. If we look only at families where the survey respondent is under age 65, we see that families with and without children are equally likely to be struggling to get by and to experience a hardship, but families with children are still more likely to spend more than their incomes. This suggests that older families are doing better than younger families. Because many of these adults are retired and not earning income, households headed by adults 65 years and older have a lower median income than the general population: $40,000 versus $54,000 in 2014 (US Census Bureau 2014). However, these households also have higher wealth. The mean net worth of families headed by someone ages 65–74 was over $1 million in 2013, compared with just $75,500 for families with heads under age 35 (Bricker et al. 2014). Families with children are more likely to think that they are doing better than they were five years ago than families without children (47 and 38 percent, respectively; figure 3). Yet while 47 percent of families with children think they are doing better than they were in 2009, only 31 percent think they are doing better than they were in 2013 (not shown). This is consistent with recovery from the recession occurring after 2009 but before 2013. After adjusting for inflation, median incomes for families with children decreased 1.9 percent between 2009 and 2014 while incomes for families without children increased by 2.6 percent over the same period. Even though families with children appear less financially healthy than years past, they are more likely to feel their situations have improved. This feeling may reflect improved economic security as children age and child care costs decline.

Use only the information provided below to formulate your answer, and format the answer using bullet points where appropriate. Compare the financial facts and figures of families with children to families without children. Many families are in financial distress, and families with children are especially vulnerable. Thirty-eight percent of families with children under age 18 living at home are struggling to get by, compared with 33 percent of families without children at home (figure 1). Financial distress can arise from a range of factors, from a specific hardship— 28 percent of families with children experienced a financial hardship in the past year, compared with 23 percent of families without children—to a simple lack of sufficient income. Twenty-four percent of families with children spent more than their income last year, compared with 19 percent of families without children. Raising children is expensive, and the costs have been rising over time. According to the USDA, the typical two-parent family can expect to spend between $13,000 and $15,000 per child per year for children born in 2013, meaning that the average cost of raising a child is expected to be $245,000 over 18 years (Lino 2014). A family with two children can expect to spend almost half its income on its children each year. Not only are children expensive, but families with children tend to have lower incomes than families without children. In 2014, the median income for families with children was about $62,000, compared with about $68,000 for families without children (figure 2). While men’s earnings increase after fatherhood, women with children have lower average earnings than women without children. These differences hold true even when looking only at working people and when controlling for years of experience and other attributes (Budig 2014; Pal and Waldfogel 2014). As single-mother families become more common, the “fatherhood bump” no longer offsets the “motherhood penalty” for many families. Public benefits are not enough to offset the increased cost of having children. Available federal programs such as Medicaid, SNAP (the Supplemental Nutrition Assistance Program), and TANF, as well as tax incentives such as the EITC (the earned income tax credit) lift millions of families with children out of poverty (Sherman, Trisi, and Parrott 2013), but they are often not enough to lift families out of financial distress. Many of the programs that focus on families with children are shrinking, despite the increased costs of having children. Total federal spending on children, currently 10 percent of the federal budget, is projected to decline to less than 8 percent in 2025, while adult Social Security, Medicare, and Medicaid spending is projected to increase to 49 percent (Isaacs et al. 2015). Some of the differences between families with and without children at home may be attributable to older families whose children are no longer at home or younger families who do not have children yet, rather than adults of childrearing age without children. If we look only at families where the survey respondent is under age 65, we see that families with and without children are equally likely to be struggling to get by and to experience a hardship, but families with children are still more likely to spend more than their incomes. This suggests that older families are doing better than younger families. Because many of these adults are retired and not earning income, households headed by adults 65 years and older have a lower median income than the general population: $40,000 versus $54,000 in 2014 (US Census Bureau 2014). However, these households also have higher wealth. The mean net worth of families headed by someone ages 65–74 was over $1 million in 2013, compared with just $75,500 for families with heads under age 35 (Bricker et al. 2014). Families with children are more likely to think that they are doing better than they were five years ago than families without children (47 and 38 percent, respectively; figure 3). Yet while 47 percent of families with children think they are doing better than they were in 2009, only 31 percent think they are doing better than they were in 2013 (not shown). This is consistent with recovery from the recession occurring after 2009 but before 2013. After adjusting for inflation, median incomes for families with children decreased 1.9 percent between 2009 and 2014 while incomes for families without children increased by 2.6 percent over the same period. Even though families with children appear less financially healthy than years past, they are more likely to feel their situations have improved. This feeling may reflect improved economic security as children age and child care costs decline.

You will only respond using the given context and include no information not readily available in the text.

What were the immediate and long-term impacts of Right-to-Work laws on employment and wages?

Federal Policies and American Labor Relations The National Labor Relations Act/Wagner Act (NLRA) of 1935 was passed by Congress to protect workers’ rights to unionization. NLRA states and defines the rights of employees to organize and bargain collectively with their employers through representatives of their own choosing (i.e., elected union leaders). The NLRA identified workers’ rights to form a union, join a union, and to strike in an effort to secure better working conditions (National Labor Relations Board, 1997). “The act also created a new National Labor Relations Board (NLRB) to arbitrate deadlocked labor- management disputes, guarantee democratic union elections and penalize unfair labor practices by employers” (Cooper, 2004, p. 2). Furthermore, NLRA prohibited employers from setting up a company union and firing or otherwise discriminating against workers who organized or joined unions (Encyclopedia Britannica, 2007). Prior to the passage of NLRA, the federal government had been largely antagonistic to union organizing. Labor unions across the country faced significant challenges in social action initiatives aimed at ensuring adequate wages, benefits and the reduction of industry health hazards. During the first half of the twentieth century, for example, laborers who attempted to organize protective associations frequently found themselves prosecuted for and convicted of conspiracy (to do what?) (Beik, 2005). With the onset of the Great Depression, and an unemployment rate of 24.9 percent in 1933 , the national political framework shifted its focus from the protection of the business sector to the protection of workers and individuals through the creation of New Deal policies (e.g., Social Security and Civilian Conservation Corps). These policies hoped to create a social safety net that would prevent further economic disaster. Due to the power of business interests and persons advocating a free market society, many New Deal policies had been declared unconstitutional by the United States Supreme Court, including the previous labor legislation – the National Industry Recovery Act of 1933 which authorized the President to regulate businesses in the interests of promoting fair competition, supporting prices and competition, creating jobs for the unemployed, and stimulating the United States economy to recover from the Great Depression (Babson, 1999). Thus, many businesses believed that the NLRA would follow the same path. In April of 1937, however, the NLRA was declared constitutional by the Supreme Court, highlighting the increased power of labor unions on national politics and policymaking (Beik, 2005). In 1935, 15 percent of American workers were unionized. By 1945, the proportion had risen to 35 percent (Babson, 1999). During this time there were three primary types of union/employer structural arrangements: the agency shop, the union shop, and the closed shop. Cooper (2004) describes the arrangements as follows: • Agency Shop: The union’s contract does not mandate that all employees join the union, but it does mandate that the employees pay agency fees. • Union Shop: The union’s contract requires that all employees join the union within a specified amount of time after becoming employed. • Closed Shop: The union’s contract mandates that the employer only hire union members (pg. 2). 1945 marked the peak of American unionization with over one-third of American workers belonging to labor unions. Organized labor reached the zenith of its power in the U.S. from 1935 – 1947 (Beik, 2005). Many business leaders, however, began to lobby for a loosening of union power insisting that businesses and individuals were, due to the NLRA, prevented from exercising their right of association and employment procedures. At the same time, the political landscape was changing and anti-communism was used as a key argument to stymie the power of unions. Labor unions were seen as a corrupt socialist tactic and, thus, could be associated with the red scare. The public also began to demand action after the World War Two coal strikes and the postwar strikes in steel, autos and other industries were perceived to have damaged the economy. With the increasing constituent pressure and the election in 1944 of the pro-business and pro-states’ rights Republican congress, the second significant piece of national labor legislation was passed, the 1947 Taft-Hartley Act. Taft-Hartley effectively overturned many of the rights guaranteed by NLRA and outlawed the closed shop arrangement (Cooper, 2004). Moreover, “section 14(b) of Taft-Hartley made Right-to-Work laws legal and gave states the power to pass laws to outlaw both agency and union shops” (Cooper, 2004, p. 10). This provision afforded states the opportunity to pass laws that forbade the establishment of businesses and/or union contracts where union membership was a condition of employment; thus, the age of RTW began. Right-to-Work Laws Immediately following the passage of the Taft-Hartley Act states began to enact Right-to- Work laws. The basic concept of RTW is that workers should not be obligated to join or give support to a union as a condition of employment (Kersey, 2007).2 The main objectives of RTW laws have, to this day, shared similar purposes. These objectives include: a. the promotion of individual freedom; b. the creation of a pro-business atmosphere aimed at spurring economic growth; c. the elimination of the power of union organization. As of January 1, 2006, 22 states had passed RTW legislation. It is important to note that a regional divide exists with regard to the establishment of RTW laws... most of the states with RTW laws are located in the southeast, Midwest and Rocky Mountain States. These states have traditionally maintained lower rates of unionization -- 18% in 1947, 52% lower than their non-RTW counterparts (Beik, 1998). Right-to-Work Laws and Employment One of the key arguments offered by proponents of RTW legislation is that the laws increase employment. Proponents believe that, if businesses are not required to operate under union wage contracts, they will remain profitable due to decreased labor costs and the economic landscape will encourage cross-state relocation of businesses; thus, employment opportunities will increase for all citizens. “Opponents, however, argue that most job growth occurs from in-state business expansion not the relocation of businesses from a non-RTW to a RTW state” (Oklahoma League of Economists, 1996, paragraph 2). The unemployment rates in RTW states pre and post RTW passage, as well as the comparison of RTW to non-RTW states, provide important insights in to the impact of RTW legislation on employment across jurisdictions. Overall, the unemployment rates in RTW states are lower than non-RTW states. For example, the unemployment rate between 1978 and 2000 averaged 5.8percent in RTW states versus 6.3percent in non-RTW states. Additionally, between 1970 and 2000 overall employment increased by 2.9percent annually in RTW states versus 2.0percent in non-RTW states. This trend has continued, although tightening, into the 2000s; between 2001 and 2006 RTW states had a median 4.8percent unemployment rate compared to 5.1 percent for non-RTW states (Kersey, 2007). As of March 2010, RTW states had an average unemployment rate of 8.6% while the rate in non-RTW states stood at 9.4% (Bureau of Labor Statistics [BLS], 2010). Another aspect of the impact that RTW laws have on employment relates to the type and condition of employment between the two types of states. The share of manufacturing employment in the U.S. in 1950 was 35percent of the workforce. This figure declined to 13 percent in 2004 (Fischer & Rupert, 2005). Many RTW advocates believe pro-business laws, such as RTW, lessen manufacturing losses by creating a conducive business atmosphere. While both types of states have not been able to stem the national tide, data indicates that manufacturing employment in RTW states has decreased at a much lower rate than in their non-RTW counterparts where manufacturing employment has seen significant decreases. Between 2001 and 2006 the typical RTW state saw manufacturing employment decline 1.5percent annually, equaling 7.1percent overall. Non-RTW states, however, faced even sharper declines, averaging 3.0 percent annually and 13.7 percent over the five year period. Every non-RTW state but one, Alaska, lost manufacturing jobs during that period, while five RTW states registered at least modest gains in this area (Wright, 2007). In terms of job conditions, the government data shows that in 2003 the rate of workplace fatalities per 100,000 workers was highest in right-to-work states. The rate of workplace deaths is 51 percent higher in RTW states (BLS, 2006). Nineteen of the top 25 states for worker fatality rates were RTW states, while three of the bottom 25 states were RTW states (Bureau of Labor Statistics [BLS], 2003). Further, in a study of New York City construction site fatalities, it was found that 93 percent of deaths happened at non-union sites (Walter, 2007). The same holds true in the coal mining industry where 87 percent of fatalities between 2007 and 2009 occurred at non-union mines (U.S. House of Representatives Committee on Education and Labor, 2007). Right-to-Work and Job Growth Holmes (1998) argues that large manufacturing establishments are more likely to be attracted to RTW states because larger plants are more likely to be unionized. RTW laws, according to manufacturers, help maintain competiveness and encourage development in the strained sector. He also found that eight of the ten states with the highest manufacturing employment growth rates are RTW states. All ten states with the lowest growth rates are non-RTW states. Opponents charge that the laws depress individual worker wages at the expense of profits and capitalist objectives. From 1977 through 1999, Gross State Product (GSP), the market value of all goods and services produced in a state, increased 0.5 percent faster in RTW states than in non-RTW states (Wilson, 2002). Right-to-Work Laws and Wages One condition of employment is the impact of RTW laws on wages. This includes both absolute wages and the overall wage distribution across income and racial lines following RTW passage. There are currently 132,604,980 workers in the United States (U.S.). The American worker, as of July 2009, earned an average of $44,901 per year. This translates in to an average hourly wage of $22.36 (Bureau of Labor Statistics [BLS], 2009). Leading researchers disagree on the impact of RTW laws on wages. For example, 16 of the 18 states are estimated to have had higher average wages in 2000 as a result of their RTW status (Reed, 2003). On the other hand, Bureau of Labor Statistics (BLS) data reveals that average annual pay is higher in non-RTW states. In addition, income polarization is higher in RTW states, with a higher percentage of workers earning the minimum wage (even when controlling for education level) than in non-RTW states. After years of economic development, the portion of heads of household earning around the minimum wage is still 35.5 percent (4.4 percentage points) higher in RTW than in high-union-density states" (Cassell, 2001). Lawrence Mishel (2001) of the Economic Policy Institute found that in 2000 the median wage for workers living in RTW states was $11.45, while wages for those living in non -RTW states were $13.00, indicating that wages were 11.9 percent lower in RTW states. He further concluded that previous research citing wage increases in RTW states were directly attributable to the improved income characteristics of those residing in large cities located on a state border with a non-RTW state. At the same time, when looking at weekly and hourly wages by industry between RTW and non-RTW states adjusted for cost-of-living, RTW states have higher wages in two key industries. For example, in manufacturing workers in RTW states earn an average of $717 weekly and $17.89 hourly while their non-RTW counterparts earn $672 and $16.80. In education and health services, those amounts are $717 and $21.34 for RTW and $650 and $20.06 for non-RTW. These differing statistics question the true RTW impact on wage increases and the quality of employment.

You will only respond using the given context and include no information not readily available in the text. What were the immediate and long-term impacts of Right-to-Work laws on employment and wages? Federal Policies and American Labor Relations The National Labor Relations Act/Wagner Act (NLRA) of 1935 was passed by Congress to protect workers’ rights to unionization. NLRA states and defines the rights of employees to organize and bargain collectively with their employers through representatives of their own choosing (i.e., elected union leaders). The NLRA identified workers’ rights to form a union, join a union, and to strike in an effort to secure better working conditions (National Labor Relations Board, 1997). “The act also created a new National Labor Relations Board (NLRB) to arbitrate deadlocked labor- management disputes, guarantee democratic union elections and penalize unfair labor practices by employers” (Cooper, 2004, p. 2). Furthermore, NLRA prohibited employers from setting up a company union and firing or otherwise discriminating against workers who organized or joined unions (Encyclopedia Britannica, 2007). Prior to the passage of NLRA, the federal government had been largely antagonistic to union organizing. Labor unions across the country faced significant challenges in social action initiatives aimed at ensuring adequate wages, benefits and the reduction of industry health hazards. During the first half of the twentieth century, for example, laborers who attempted to organize protective associations frequently found themselves prosecuted for and convicted of conspiracy (to do what?) (Beik, 2005). With the onset of the Great Depression, and an unemployment rate of 24.9 percent in 1933 , the national political framework shifted its focus from the protection of the business sector to the protection of workers and individuals through the creation of New Deal policies (e.g., Social Security and Civilian Conservation Corps). These policies hoped to create a social safety net that would prevent further economic disaster. Due to the power of business interests and persons advocating a free market society, many New Deal policies had been declared unconstitutional by the United States Supreme Court, including the previous labor legislation – the National Industry Recovery Act of 1933 which authorized the President to regulate businesses in the interests of promoting fair competition, supporting prices and competition, creating jobs for the unemployed, and stimulating the United States economy to recover from the Great Depression (Babson, 1999). Thus, many businesses believed that the NLRA would follow the same path. In April of 1937, however, the NLRA was declared constitutional by the Supreme Court, highlighting the increased power of labor unions on national politics and policymaking (Beik, 2005). In 1935, 15 percent of American workers were unionized. By 1945, the proportion had risen to 35 percent (Babson, 1999). During this time there were three primary types of union/employer structural arrangements: the agency shop, the union shop, and the closed shop. Cooper (2004) describes the arrangements as follows: • Agency Shop: The union’s contract does not mandate that all employees join the union, but it does mandate that the employees pay agency fees. • Union Shop: The union’s contract requires that all employees join the union within a specified amount of time after becoming employed. • Closed Shop: The union’s contract mandates that the employer only hire union members (pg. 2). 1945 marked the peak of American unionization with over one-third of American workers belonging to labor unions. Organized labor reached the zenith of its power in the U.S. from 1935 – 1947 (Beik, 2005). Many business leaders, however, began to lobby for a loosening of union power insisting that businesses and individuals were, due to the NLRA, prevented from exercising their right of association and employment procedures. At the same time, the political landscape was changing and anti-communism was used as a key argument to stymie the power of unions. Labor unions were seen as a corrupt socialist tactic and, thus, could be associated with the red scare. The public also began to demand action after the World War Two coal strikes and the postwar strikes in steel, autos and other industries were perceived to have damaged the economy. With the increasing constituent pressure and the election in 1944 of the pro-business and pro-states’ rights Republican congress, the second significant piece of national labor legislation was passed, the 1947 Taft-Hartley Act. Taft-Hartley effectively overturned many of the rights guaranteed by NLRA and outlawed the closed shop arrangement (Cooper, 2004). Moreover, “section 14(b) of Taft-Hartley made Right-to-Work laws legal and gave states the power to pass laws to outlaw both agency and union shops” (Cooper, 2004, p. 10). This provision afforded states the opportunity to pass laws that forbade the establishment of businesses and/or union contracts where union membership was a condition of employment; thus, the age of RTW began. Right-to-Work Laws Immediately following the passage of the Taft-Hartley Act states began to enact Right-to- Work laws. The basic concept of RTW is that workers should not be obligated to join or give support to a union as a condition of employment (Kersey, 2007).2 The main objectives of RTW laws have, to this day, shared similar purposes. These objectives include: a. the promotion of individual freedom; b. the creation of a pro-business atmosphere aimed at spurring economic growth; c. the elimination of the power of union organization. As of January 1, 2006, 22 states had passed RTW legislation. It is important to note that a regional divide exists with regard to the establishment of RTW laws... most of the states with RTW laws are located in the southeast, Midwest and Rocky Mountain States. These states have traditionally maintained lower rates of unionization -- 18% in 1947, 52% lower than their non-RTW counterparts (Beik, 1998). Right-to-Work Laws and Employment One of the key arguments offered by proponents of RTW legislation is that the laws increase employment. Proponents believe that, if businesses are not required to operate under union wage contracts, they will remain profitable due to decreased labor costs and the economic landscape will encourage cross-state relocation of businesses; thus, employment opportunities will increase for all citizens. “Opponents, however, argue that most job growth occurs from in-state business expansion not the relocation of businesses from a non-RTW to a RTW state” (Oklahoma League of Economists, 1996, paragraph 2). The unemployment rates in RTW states pre and post RTW passage, as well as the comparison of RTW to non-RTW states, provide important insights in to the impact of RTW legislation on employment across jurisdictions. Overall, the unemployment rates in RTW states are lower than non-RTW states. For example, the unemployment rate between 1978 and 2000 averaged 5.8percent in RTW states versus 6.3percent in non-RTW states. Additionally, between 1970 and 2000 overall employment increased by 2.9percent annually in RTW states versus 2.0percent in non-RTW states. This trend has continued, although tightening, into the 2000s; between 2001 and 2006 RTW states had a median 4.8percent unemployment rate compared to 5.1 percent for non-RTW states (Kersey, 2007). As of March 2010, RTW states had an average unemployment rate of 8.6% while the rate in non-RTW states stood at 9.4% (Bureau of Labor Statistics [BLS], 2010). Another aspect of the impact that RTW laws have on employment relates to the type and condition of employment between the two types of states. The share of manufacturing employment in the U.S. in 1950 was 35percent of the workforce. This figure declined to 13 percent in 2004 (Fischer & Rupert, 2005). Many RTW advocates believe pro-business laws, such as RTW, lessen manufacturing losses by creating a conducive business atmosphere. While both types of states have not been able to stem the national tide, data indicates that manufacturing employment in RTW states has decreased at a much lower rate than in their non-RTW counterparts where manufacturing employment has seen significant decreases. Between 2001 and 2006 the typical RTW state saw manufacturing employment decline 1.5percent annually, equaling 7.1percent overall. Non-RTW states, however, faced even sharper declines, averaging 3.0 percent annually and 13.7 percent over the five year period. Every non-RTW state but one, Alaska, lost manufacturing jobs during that period, while five RTW states registered at least modest gains in this area (Wright, 2007). In terms of job conditions, the government data shows that in 2003 the rate of workplace fatalities per 100,000 workers was highest in right-to-work states. The rate of workplace deaths is 51 percent higher in RTW states (BLS, 2006). Nineteen of the top 25 states for worker fatality rates were RTW states, while three of the bottom 25 states were RTW states (Bureau of Labor Statistics [BLS], 2003). Further, in a study of New York City construction site fatalities, it was found that 93 percent of deaths happened at non-union sites (Walter, 2007). The same holds true in the coal mining industry where 87 percent of fatalities between 2007 and 2009 occurred at non-union mines (U.S. House of Representatives Committee on Education and Labor, 2007). Right-to-Work and Job Growth Holmes (1998) argues that large manufacturing establishments are more likely to be attracted to RTW states because larger plants are more likely to be unionized. RTW laws, according to manufacturers, help maintain competiveness and encourage development in the strained sector. He also found that eight of the ten states with the highest manufacturing employment growth rates are RTW states. All ten states with the lowest growth rates are non-RTW states. Opponents charge that the laws depress individual worker wages at the expense of profits and capitalist objectives. From 1977 through 1999, Gross State Product (GSP), the market value of all goods and services produced in a state, increased 0.5 percent faster in RTW states than in non-RTW states (Wilson, 2002). Right-to-Work Laws and Wages One condition of employment is the impact of RTW laws on wages. This includes both absolute wages and the overall wage distribution across income and racial lines following RTW passage. There are currently 132,604,980 workers in the United States (U.S.). The American worker, as of July 2009, earned an average of $44,901 per year. This translates in to an average hourly wage of $22.36 (Bureau of Labor Statistics [BLS], 2009). Leading researchers disagree on the impact of RTW laws on wages. For example, 16 of the 18 states are estimated to have had higher average wages in 2000 as a result of their RTW status (Reed, 2003). On the other hand, Bureau of Labor Statistics (BLS) data reveals that average annual pay is higher in non-RTW states. In addition, income polarization is higher in RTW states, with a higher percentage of workers earning the minimum wage (even when controlling for education level) than in non-RTW states. After years of economic development, the portion of heads of household earning around the minimum wage is still 35.5 percent (4.4 percentage points) higher in RTW than in high-union-density states" (Cassell, 2001). Lawrence Mishel (2001) of the Economic Policy Institute found that in 2000 the median wage for workers living in RTW states was $11.45, while wages for those living in non -RTW states were $13.00, indicating that wages were 11.9 percent lower in RTW states. He further concluded that previous research citing wage increases in RTW states were directly attributable to the improved income characteristics of those residing in large cities located on a state border with a non-RTW state. At the same time, when looking at weekly and hourly wages by industry between RTW and non-RTW states adjusted for cost-of-living, RTW states have higher wages in two key industries. For example, in manufacturing workers in RTW states earn an average of $717 weekly and $17.89 hourly while their non-RTW counterparts earn $672 and $16.80. In education and health services, those amounts are $717 and $21.34 for RTW and $650 and $20.06 for non-RTW. These differing statistics question the true RTW impact on wage increases and the quality of employment.

Respond only using information contained within the prompt. Do not use any external information or knowledge when answering. Answer as a non-expert only. Give your answer simply with easy to understand language.

What are the potential harmful side effects of semaglutide?

According to the EPAR for semaglutide, eight completed phase 3 trials and a cardiovascular outcomes trial provided safety data relating to approximately 4,800 patients and over 5,600 patient years of exposure. [12] Additional safety data is also available from the SUSTAIN 7 which assessed semaglutide and dulaglutide. [9] Adverse events The EPAR states that “The safety profile of semaglutide is generally consistent with those reported for other drugs in the GLP-1 RA class”. The EMA noted that the rates of gastrointestinal adverse events were higher for semaglutide compared to exenatide, sitagliptin and insulin glargine. [12] However the open label SUSTAIN 7 study found that the frequency of gastrointestinal adverse effects were similar between semaglutide and dulaglutide groups. [9] A significantly increased risk of diabetic retinopathy complications was observed with semaglutide as compared with placebo. This increased risk was particularly marked in patients with preexisting diabetic retinopathy at baseline and co-use of insulin. Although it is recognised that intensified glycaemic control may precipitate early worsening of diabetic retinopathy, clinical trials data did not demonstrate a decrease in the risk of diabetic retinopathy over the course of two years, and data also suggests that semaglutide was associated with retinopathy in patients with only small HbA1c reductions. [12] A specific warning has been included in the SPC for semaglutide outlining the increased risk of diabetic retinopathy complications in patients with existing diabetic retinopathy treated with insulin. [15] The SPC for semaglutide lists the following adverse events [13]: Table 2. Adverse reactions from long-term controlled phase 3a trials including the cardiovascular 7 Date: December 2018 outcomes trial. MedDRA system organ class Very common Common Uncommon Rare Immune system disorders Anaphylactic reaction Metabolism and nutrition disorders Hypoglycaemia when used with insulin or sulfonylurea Hypoglycaemia when used with other OADs Decreased appetite Nervous system disorders Dizziness Dysgeusia Eye disorders Diabetic retinopathy complications Cardiac disorders Increased heart rate Gastrointestinal disorders Nausea Diarrhoea Vomiting Abdominal pain Abdominal distension Constipation Dyspepsia Gastritis Gastrooesophageal reflux disease Eructation Flatulence Hepatobiliary disorders Cholelithiasis General disorders and administration site conditions Fatigue Injection site reactions Investigations Increased lipase Increased amylase Weight decreased

What are the potential harmful side effects of semaglutide? Respond only using information contained within the prompt. Do not use any external information or knowledge when answering. Answer as a non-expert only. Give your answer simply with easy to understand language. The text: According to the EPAR for semaglutide, eight completed phase 3 trials and a cardiovascular outcomes trial provided safety data relating to approximately 4,800 patients and over 5,600 patient years of exposure. [12] Additional safety data is also available from the SUSTAIN 7 which assessed semaglutide and dulaglutide. [9] Adverse events The EPAR states that “The safety profile of semaglutide is generally consistent with those reported for other drugs in the GLP-1 RA class”. The EMA noted that the rates of gastrointestinal adverse events were higher for semaglutide compared to exenatide, sitagliptin and insulin glargine. [12] However the open label SUSTAIN 7 study found that the frequency of gastrointestinal adverse effects were similar between semaglutide and dulaglutide groups. [9] A significantly increased risk of diabetic retinopathy complications was observed with semaglutide as compared with placebo. This increased risk was particularly marked in patients with preexisting diabetic retinopathy at baseline and co-use of insulin. Although it is recognised that intensified glycaemic control may precipitate early worsening of diabetic retinopathy, clinical trials data did not demonstrate a decrease in the risk of diabetic retinopathy over the course of two years, and data also suggests that semaglutide was associated with retinopathy in patients with only small HbA1c reductions. [12] A specific warning has been included in the SPC for semaglutide outlining the increased risk of diabetic retinopathy complications in patients with existing diabetic retinopathy treated with insulin. [15] The SPC for semaglutide lists the following adverse events [13]: Table 2. Adverse reactions from long-term controlled phase 3a trials including the cardiovascular 7 Date: December 2018 outcomes trial. MedDRA system organ class Very common Common Uncommon Rare Immune system disorders Anaphylactic reaction Metabolism and nutrition disorders Hypoglycaemia when used with insulin or sulfonylurea Hypoglycaemia when used with other OADs Decreased appetite Nervous system disorders Dizziness Dysgeusia Eye disorders Diabetic retinopathy complications Cardiac disorders Increased heart rate Gastrointestinal disorders Nausea Diarrhoea Vomiting Abdominal pain Abdominal distension Constipation Dyspepsia Gastritis Gastrooesophageal reflux disease Eructation Flatulence Hepatobiliary disorders Cholelithiasis General disorders and administration site conditions Fatigue Injection site reactions Investigations Increased lipase Increased amylase Weight decreased

Only use information contained in the prompt to answer your questions. Use bulleted formatting when listing more than 2 items. If listing cases, use italic formatting for the case names. If there's not enough information available to answer a question then state so but answer the parts that you can, if any.

What conclusions were reached by the courts in the cases mentioned in the excerpt below regarding AI, including generative AI?

State v. Loomis, 371 Wis.2d 235, 881 N.W.2d 749 (2016), cert. denied, 137 S. Ct. 2290 (2017) The defendant was convicted of various offenses arising out of a drive-by shooting. His presentence report included an evidence-based risk assessment that indicated a high risk of recidivism. On appeal, the defendant argued that consideration of the risk assessment by the sentencing judge violated his right to due process. The Supreme Court rejected the argument. However, it imposed conditions on the use of risk assessments. State v. Morrill, No. A-1-CA-36490, 2019 WL 3765586 (N.M. App. July 24, 2019) Defendant asks this Court to ‘find that the attestations made by a computer program constitute ‘statements,’ whether attributable to an artificial intelligence software or the software developer who implicitly offers the program’s conclusions as their own.’ (Emphasis omitted.) Based on that contention, Defendant further argues that the automated conclusions from Roundup and Forensic Toolkit constitute inadmissible hearsay statements that are not admissible under the business record exception. In so arguing, Defendant acknowledges that such a holding would diverge from the plain language of our hearsay rule’s relevant definitions that reference statements of a ‘person.’ *** Based on the following, we conclude the district court correctly determined that the computer generated evidence produced by Roundup and Forensic Toolkit was 11 not hearsay. Agent Peña testified that his computer runs Roundup twenty-four hours a day, seven days a week and automatically attempts to make connections with and downloads from IP addresses that are suspected to be sharing child pornography. As it does so, Roundup logs every action it takes. Detective Hartsock testified that Forensic Toolkit organizes information stored on seized electronic devices into various categories including graphics, videos, word documents, and internet history. Because the software programs make the relevant assertions, without any intervention or modification by a person using the software, we conclude that the assertions are not statements by a person governed by our hearsay rules. State v. Pickett, 466 N.J. Super. 270 (App. Div. 2021), motions to expand record, for leave to appeal, and for stay denied, State v. Pickett, 246 N.J. 48 (2021) In this case of first impression addressing the proliferation of forensic evidentiary technology in criminal prosecutions, we must determine whether defendant is entitled to trade secrets of a private company for the sole purpose of challenging at a Frye hearing the reliability of the science underlying novel DNA analysis software and expert testimony. At the hearing, the State produced an expert who relied on his company’s complex probabilistic genotyping software program to testify that defendant’s DNA was present, thereby connecting defendant to a murder and other crimes. Before crossexamination of the expert, the judge denied defendant access to the trade secrets, which include the software’s source code and related documentation. This is the first appeal in New Jersey addressing the science underlying the proffered testimony by the State’s expert, who designed, utilized, and relied upon TrueAllele, the program at issue. TrueAllele is technology not yet used or tested in New Jersey; it is designed to address intricate interpretational challenges of testing low levels or complex mixtures of DNA. TrueAllele’s computer software utilizes and implements an elaborate mathematical model to estimate the statistical probability that a particular individual’s DNA is consistent with data from a given sample, as compared with genetic material from another, unrelated individual from the broader relevant population. For this reason, TrueAllele, and other probabilistic genotyping software, marks a profound shift in DNA forensics. TrueAllele’s software integrates multiple scientific disciplines. At issue here—in determining the reliability of TrueAllele—is whether defendant is entitled to the trade secrets to cross-examine the State’s expert at the Frye hearing to challenge whether his testimony has gained general acceptance within the computer science community, which is one of the disciplines. The defense expert’s access to the proprietary information is directly relevant to that question and would allow that expert to independently test whether the evidentiary software operates as intended. Without that opportunity, 12 defendant is relegated to blindly accepting the company’s assertions as to its reliability. And importantly, the judge would be unable to reach an informed reliability determination at the Frye hearing as part of his gatekeeping function. Hiding the source code is not the answer. The solution is producing it under a protective order. Doing so safeguards the company’s intellectual property rights and defendant’s constitutional liberty interest alike. Intellectual property law aims to prevent business competitorsfrom stealing confidential commercial information in the marketplace; it was never meant to justify concealing relevant information from parties to a criminal prosecution in the context of a Frye hearing. [footnote omitted]. State v. Saylor, 2019 Ohio 1025 (Ct. App. 2019) (concurring opinion of Froelich, J.) {¶ 49} Saylor is a 27-year-old heroin addict, who the court commented has ‘no adult record [* * * and] has led a law-abiding life for a significant number of years’; his juvenile record, according to the prosecutor, was ‘virtually nothing.’ The prosecutor requested an aggregate sentence of five to seven years, and defense counsel requested a three-year sentence. The trial court sentenced Saylor to 12 1/2 years in prison. Although it found Saylor to be indigent and did not impose the mandatory fine, the court imposed a $500 fine and assessed attorney fees and costs; the court also specifically disapproved a Risk Reduction sentence or placement in the Intensive Program Prison (IPP). {¶ 50} I have previously voiced my concerns about the almost unfettered discretion available to a sentencing court when the current case law apparently does not permit a review for abuse of discretion. State v. Roberts, 2d Dist. Clark No. 2017-CA-98, 2018-Ohio4885, ¶ 42-45, (Froelich, J., dissenting). However, in this case, the trial court considered the statutory factors in R.C. 2929.11 and R.C. 2929.12, the individual sentences were within the statutory ranges, and the court’s consecutive sentencing findings, including the course-of-conduct finding under R.C. 2929.14(C)(4)(b), were supported by the record. {¶ 51} As for the trial court’s consideration of ORAS, the ‘algorithmization’ of sentencing is perhaps a good-faith attempt to remove unbridled discretion – and its inherent biases – from sentencing. Compare State v. Lawson, 2018-Ohio-1532, 111 N.E.3d 98, ¶ 20-21 (2d Dist.) (Froelich, J., concurring). However, ‘recidivism risk modeling still involves human choices about what characteristics and factors should be assessed, what hierarchy governs their application, and what relative weight should be ascribed to each.’ Hillman, The Use of Artificial Intelligence in Gauging the Risk of Recidivism, 58 The Judges Journal 40 (2019). {¶ 52} The court’s statement that the ‘moderate’ score was ‘awfully high,’ given the lack of criminal history, could imply that the court believed there must be other factors reflected in the score that increased Saylor’s probable recidivism. There is nothing on this record to refute or confirm the relevance of Saylor’s ORAS score or any ORAS score. 13 Certainly, the law of averages is not the law. The trial court’s comment further suggested that its own assessment of Saylor’s risk of recidivism differed from the ORAS score. The decision of the trial court is not clearly and convincingly unsupported by the record, regardless of any weight potentially given to the ORAS score by the trial court. Therefore, on this record, I find no basis for reversal

Only use information contained in the prompt to answer your questions. Use bulleted formatting when listing more than 2 items. If listing cases, use italic formatting for the case names. If there's not enough information available to answer a question then state so but answer the parts that you can, if any. What conclusions were reached by the courts in the cases mentioned in the excerpt below regarding AI, including generative AI? State v. Loomis, 371 Wis.2d 235, 881 N.W.2d 749 (2016), cert. denied, 137 S. Ct. 2290 (2017) The defendant was convicted of various offenses arising out of a drive-by shooting. His presentence report included an evidence-based risk assessment that indicated a high risk of recidivism. On appeal, the defendant argued that consideration of the risk assessment by the sentencing judge violated his right to due process. The Supreme Court rejected the argument. However, it imposed conditions on the use of risk assessments. State v. Morrill, No. A-1-CA-36490, 2019 WL 3765586 (N.M. App. July 24, 2019) Defendant asks this Court to ‘find that the attestations made by a computer program constitute ‘statements,’ whether attributable to an artificial intelligence software or the software developer who implicitly offers the program’s conclusions as their own.’ (Emphasis omitted.) Based on that contention, Defendant further argues that the automated conclusions from Roundup and Forensic Toolkit constitute inadmissible hearsay statements that are not admissible under the business record exception. In so arguing, Defendant acknowledges that such a holding would diverge from the plain language of our hearsay rule’s relevant definitions that reference statements of a ‘person.’ *** Based on the following, we conclude the district court correctly determined that the computer generated evidence produced by Roundup and Forensic Toolkit was 11 not hearsay. Agent Peña testified that his computer runs Roundup twenty-four hours a day, seven days a week and automatically attempts to make connections with and downloads from IP addresses that are suspected to be sharing child pornography. As it does so, Roundup logs every action it takes. Detective Hartsock testified that Forensic Toolkit organizes information stored on seized electronic devices into various categories including graphics, videos, word documents, and internet history. Because the software programs make the relevant assertions, without any intervention or modification by a person using the software, we conclude that the assertions are not statements by a person governed by our hearsay rules. State v. Pickett, 466 N.J. Super. 270 (App. Div. 2021), motions to expand record, for leave to appeal, and for stay denied, State v. Pickett, 246 N.J. 48 (2021) In this case of first impression addressing the proliferation of forensic evidentiary technology in criminal prosecutions, we must determine whether defendant is entitled to trade secrets of a private company for the sole purpose of challenging at a Frye hearing the reliability of the science underlying novel DNA analysis software and expert testimony. At the hearing, the State produced an expert who relied on his company’s complex probabilistic genotyping software program to testify that defendant’s DNA was present, thereby connecting defendant to a murder and other crimes. Before crossexamination of the expert, the judge denied defendant access to the trade secrets, which include the software’s source code and related documentation. This is the first appeal in New Jersey addressing the science underlying the proffered testimony by the State’s expert, who designed, utilized, and relied upon TrueAllele, the program at issue. TrueAllele is technology not yet used or tested in New Jersey; it is designed to address intricate interpretational challenges of testing low levels or complex mixtures of DNA. TrueAllele’s computer software utilizes and implements an elaborate mathematical model to estimate the statistical probability that a particular individual’s DNA is consistent with data from a given sample, as compared with genetic material from another, unrelated individual from the broader relevant population. For this reason, TrueAllele, and other probabilistic genotyping software, marks a profound shift in DNA forensics. TrueAllele’s software integrates multiple scientific disciplines. At issue here—in determining the reliability of TrueAllele—is whether defendant is entitled to the trade secrets to cross-examine the State’s expert at the Frye hearing to challenge whether his testimony has gained general acceptance within the computer science community, which is one of the disciplines. The defense expert’s access to the proprietary information is directly relevant to that question and would allow that expert to independently test whether the evidentiary software operates as intended. Without that opportunity, 12 defendant is relegated to blindly accepting the company’s assertions as to its reliability. And importantly, the judge would be unable to reach an informed reliability determination at the Frye hearing as part of his gatekeeping function. Hiding the source code is not the answer. The solution is producing it under a protective order. Doing so safeguards the company’s intellectual property rights and defendant’s constitutional liberty interest alike. Intellectual property law aims to prevent business competitorsfrom stealing confidential commercial information in the marketplace; it was never meant to justify concealing relevant information from parties to a criminal prosecution in the context of a Frye hearing. [footnote omitted]. State v. Saylor, 2019 Ohio 1025 (Ct. App. 2019) (concurring opinion of Froelich, J.) {¶ 49} Saylor is a 27-year-old heroin addict, who the court commented has ‘no adult record [* * * and] has led a law-abiding life for a significant number of years’; his juvenile record, according to the prosecutor, was ‘virtually nothing.’ The prosecutor requested an aggregate sentence of five to seven years, and defense counsel requested a three-year sentence. The trial court sentenced Saylor to 12 1/2 years in prison. Although it found Saylor to be indigent and did not impose the mandatory fine, the court imposed a $500 fine and assessed attorney fees and costs; the court also specifically disapproved a Risk Reduction sentence or placement in the Intensive Program Prison (IPP). {¶ 50} I have previously voiced my concerns about the almost unfettered discretion available to a sentencing court when the current case law apparently does not permit a review for abuse of discretion. State v. Roberts, 2d Dist. Clark No. 2017-CA-98, 2018-Ohio4885, ¶ 42-45, (Froelich, J., dissenting). However, in this case, the trial court considered the statutory factors in R.C. 2929.11 and R.C. 2929.12, the individual sentences were within the statutory ranges, and the court’s consecutive sentencing findings, including the course-of-conduct finding under R.C. 2929.14(C)(4)(b), were supported by the record. {¶ 51} As for the trial court’s consideration of ORAS, the ‘algorithmization’ of sentencing is perhaps a good-faith attempt to remove unbridled discretion – and its inherent biases – from sentencing. Compare State v. Lawson, 2018-Ohio-1532, 111 N.E.3d 98, ¶ 20-21 (2d Dist.) (Froelich, J., concurring). However, ‘recidivism risk modeling still involves human choices about what characteristics and factors should be assessed, what hierarchy governs their application, and what relative weight should be ascribed to each.’ Hillman, The Use of Artificial Intelligence in Gauging the Risk of Recidivism, 58 The Judges Journal 40 (2019). {¶ 52} The court’s statement that the ‘moderate’ score was ‘awfully high,’ given the lack of criminal history, could imply that the court believed there must be other factors reflected in the score that increased Saylor’s probable recidivism. There is nothing on this record to refute or confirm the relevance of Saylor’s ORAS score or any ORAS score. 13 Certainly, the law of averages is not the law. The trial court’s comment further suggested that its own assessment of Saylor’s risk of recidivism differed from the ORAS score. The decision of the trial court is not clearly and convincingly unsupported by the record, regardless of any weight potentially given to the ORAS score by the trial court. Therefore, on this record, I find no basis for reversal

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

I'm working on a thesis related to AI in cybersecurity and came across Google's new AI Cyber Defense Initiative. I'm trying to understand how this initiative shifts the "Defender's Dilemma" in practical terms. Can AI really anticipate threats, and if so, wouldn't this create a new challenge of false positives or over-reliance on automated systems? Also, could the open-sourcing of Magika actually expose vulnerabilities, given it's now public? How does this balance with Google's push for collaboration and security transparency?

Google LLC today announced a new AI Cyber Defense Initiative and proposed a new policy and technology agenda aimed at harnessing the power of artificial intelligence to bolster cybersecurity defenses globally. The new initiative is designed to counteract evolving threats by leveraging AI’s capabilities to enhance threat detection, automate vulnerability management and improve incident response efficiency. Google argues that the main challenge in cybersecurity is that attackers need only one successful, novel threat to break through the best defenses. On the flip side, defenders need to deploy the best defenses at all times across increasingly complex digital terrain with no margin for error. Google calls this the “Defender’s Dilemma,” and there has never been a reliable way to tip that balance. This is where AI enters the picture. Google believes AI at scale can tackle the Defender’s Dilemma. AI can do so by allowing security professionals and defenders to scale up their work in threat detection and related cybersecurity defense requirements. The AI Cyber Defense initiative aims to employ AI not only to respond to threats but to anticipate and neutralize them before they can cause harm. The idea behind the initiative is that the traditional reactive cybersecurity model is no longer sufficient in a world where cyberthreats are becoming increasingly sophisticated and pervasive. The new initiative includes deploying AI-driven algorithms designed to identify and analyze patterns indicative of cyber threats. Using data generated across its global network, Google will train AI systems to learn from the full range of threats and teach them to adapt to new tactics employed by cybercriminals. As part of the initiative, Google is also using AI to drive significant advances in vulnerability management. The idea is that by identifying vulnerabilities within software and systems, AI can significantly reduce the window of opportunity for attackers to exploit these weaknesses. Thrown into the mix is AI’s ability to suggest and implement fixes to vulnerabilities, streaming the patching process and, in doing so, further reducing the risk of a breach. The initiative further outlines the use of AI in incident response and automates the analysis of indices to identify the source, method and extent of an attack. Google is calling for a collaborative approach to recognizing the global nature of cyberthreats and calls for partnerships between industries and governments to share intelligence, best practices and advancements in AI-driven security measures. As part of the program, Google is expanding its Google.org Cybersecurity Seminars Program to cover all of Europe. Finally, Google announced today that it’s open-sourcing Magika, a new, AI-powered tool to aid defenders through file type identification, essential for detecting malware. Magika is already used to help protect products, including Gmail, Drive and Safe Browsing and is used by Google’s VirusTotal team to foster a safer digital environment. Google says Magika outperforms conventional file identification methods, providing an overall 30% accuracy boost and up to 95% higher precision on traditionally hard-to-identify but potentially problematic content such as VBA, JavaScript and Powershell. “The AI revolution is already underway,” Google concludes in a blog post on the announcements. “While people rightly applaud the promise of new medicines and scientific breakthroughs, we’re also excited about AI’s potential to solve generational security challenges while bringing us close to the safe, secure and trusted digital world we deserve.”

"================ <TEXT PASSAGE> ======= Google LLC today announced a new AI Cyber Defense Initiative and proposed a new policy and technology agenda aimed at harnessing the power of artificial intelligence to bolster cybersecurity defenses globally. The new initiative is designed to counteract evolving threats by leveraging AI’s capabilities to enhance threat detection, automate vulnerability management and improve incident response efficiency. Google argues that the main challenge in cybersecurity is that attackers need only one successful, novel threat to break through the best defenses. On the flip side, defenders need to deploy the best defenses at all times across increasingly complex digital terrain with no margin for error. Google calls this the “Defender’s Dilemma,” and there has never been a reliable way to tip that balance. This is where AI enters the picture. Google believes AI at scale can tackle the Defender’s Dilemma. AI can do so by allowing security professionals and defenders to scale up their work in threat detection and related cybersecurity defense requirements. The AI Cyber Defense initiative aims to employ AI not only to respond to threats but to anticipate and neutralize them before they can cause harm. The idea behind the initiative is that the traditional reactive cybersecurity model is no longer sufficient in a world where cyberthreats are becoming increasingly sophisticated and pervasive. The new initiative includes deploying AI-driven algorithms designed to identify and analyze patterns indicative of cyber threats. Using data generated across its global network, Google will train AI systems to learn from the full range of threats and teach them to adapt to new tactics employed by cybercriminals. As part of the initiative, Google is also using AI to drive significant advances in vulnerability management. The idea is that by identifying vulnerabilities within software and systems, AI can significantly reduce the window of opportunity for attackers to exploit these weaknesses. Thrown into the mix is AI’s ability to suggest and implement fixes to vulnerabilities, streaming the patching process and, in doing so, further reducing the risk of a breach. The initiative further outlines the use of AI in incident response and automates the analysis of indices to identify the source, method and extent of an attack. Google is calling for a collaborative approach to recognizing the global nature of cyberthreats and calls for partnerships between industries and governments to share intelligence, best practices and advancements in AI-driven security measures. As part of the program, Google is expanding its Google.org Cybersecurity Seminars Program to cover all of Europe. Finally, Google announced today that it’s open-sourcing Magika, a new, AI-powered tool to aid defenders through file type identification, essential for detecting malware. Magika is already used to help protect products, including Gmail, Drive and Safe Browsing and is used by Google’s VirusTotal team to foster a safer digital environment. Google says Magika outperforms conventional file identification methods, providing an overall 30% accuracy boost and up to 95% higher precision on traditionally hard-to-identify but potentially problematic content such as VBA, JavaScript and Powershell. “The AI revolution is already underway,” Google concludes in a blog post on the announcements. “While people rightly applaud the promise of new medicines and scientific breakthroughs, we’re also excited about AI’s potential to solve generational security challenges while bringing us close to the safe, secure and trusted digital world we deserve.” https://siliconangle.com/2024/02/15/google-announces-ai-cyber-defense-initiative-enhance-global-cybersecurity/ ================ <QUESTION> ======= I'm working on a thesis related to AI in cybersecurity and came across Google's new AI Cyber Defense Initiative. I'm trying to understand how this initiative shifts the "Defender's Dilemma" in practical terms. Can AI really anticipate threats, and if so, wouldn't this create a new challenge of false positives or over-reliance on automated systems? Also, could the open-sourcing of Magika actually expose vulnerabilities, given it's now public? How does this balance with Google's push for collaboration and security transparency? ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

You can only respond using information from the context provided. Arrange the answers in numbered list with headers.

What are the differences between the types of cells described and some life forms they make up.

CELL STRUCTURE Cells are the building blocks of life. A cell is chemical system that is able to maintain its structure and reproduce. Cells are the fundamental unit of life. All living things are cells or composed of cells. Although different living things may be as unlike as a violet and an octopus, they are all built in essentially the same way. The most basic similarity is that all living things are composed of one or more cells. This is known as the Cell Theory. Our knowledge of cells is built on work done with microscopes. English scientist Robert Hooke in 1665 first described cells from his observations of cork slices. Hooke first used the word "cell". Dutch amateur scientist Antonie van Leeuwenhoek discovered microscopic animals in water. German scientists Schleiden and Schwann in 1830's were first to say that all organisms are made of one or more cells. German biologist Virchow in 1858 stated that all cells come from the division of pre-existing cells. The Cell Theory can be summarized as: Cells are the fundamental unit of life - nothing less than a cell is alive. All organisms are constructed of and by cells. All cells arise from preexisting cells. Cells contain the information necessary for their own reproduction. No new cells are originating spontaneously on earth today. Cells are the functional units of life. All biochemical processes are carried out by cells. • Groups of cells can be organized and function as multicellular organisms Cells of multicellular organisms can become specialized in form and function to carry out subprocesses of the multicellular organism. Cells are common to all living beings, and provide information about all forms of life. Because all cells come from existing cells, scientists can study cells to learn about growth, reproduction, and all other functions that living things perform. By learning about cells and how they function, we can learn about all types of living things. Classification of cells: All living organisms (bacteria, blue green algae, plants and animals) have cellular organization and may contain one or many cells. The organisms with only one cell in their body are called unicellular organisms (bacteria, blue green algae, some algae, Protozoa, etc.). The organisms having many cells in their body are called multicellular organisms (fungi, most plants and animals). Any living organism may contain only one type of cell either A. Prokaryotic cells; B. Eukaryotic cells. The terms prokaryotic and eukaryotic were suggested by Hans Ris in the 1960’s. This classification is based on their complexity. Further based on the kingdom into which they may fall i.e the plant or the animal kingdom, plant and animal cells bear many differences. These will be studied in detail in the upcoming sections PROKARYOTIC CELLS Prokaryote comes from the Greek words for pre-nucleus. Prokaryotes: i. One circular chromosome, not contained in a membrane. ii. No histones or introns are present in Bacteria; both are found in Eukaryotes and Archaea. iii. No membrane-bound organelles. (Only contain non membrane-bound organelles). iv. Bacteria contain peptidoglycan in cell walls; Eukaryotes and Archaea do not. v. Binary fission. 2 Size, Shape, and Arrangement of Bacterial Cells. i. Average size of prokaryotic cells: 0.2 -2.0 μm in diameter 1-10 μm (0.001 – 0.01 mm) [book says 2 – 8 μm] in length. 1. Typical eukaryote 10-500 μm in length (0.01 – 0.5 mm). 2. Typical virus 20-1000 nm in length (0.00000002 – 0.000001 m). 3. Thiomargarita is the largest bacterium known. It is about the size of a typed period (0.75 mm). 4. Nanoarchaeum is the smallest cell known. It is at the lower theoretical limit for cell size (0.4 μm). ii. Basic bacterial shapes: 1. Coccus (sphere/round). 2. Bacillus (staff/rod-shaped). 3. Spirilla (rigid with a spiral/corkscrew shape). a. Flagella propel these bacteria. 4. Vibrio (curved rod). 5. Spirochetes (flexible with a spiral shape). Axial filaments (endoflagella) propel these bacteria. iii. Descriptive prefixes: 1. Diplo (two cells). 2. Tetra (four cells). 3. Sarcinae (cube of 8 cells). 4. Staphylo (clusters of cells). 5. Strepto (chains of cells). iv. Unusual bacterial shapes: 1. Star-shaped Stella. 2. Square/rectangular Haloarcula. v. Arrangements: 1. Pairs: diplococci, diplobacilli 2. Clusters: staphylococci 3. Chains: streptococci, streptobacilli. vi. Most bacteria are monomorphic. They do not change shape unless environmental conditions change. vii. A few are pleomorphic. These species have individuals that can come in a variety of shapes Structures External to the Prokaryotic Cell Wall. a. Glycocalyx (sugar coat). i. Usually very sticky. ii. Found external to cell wall. iii. Composed of polysaccharide and/or polypeptide. iv. It can be broken down and used as an energy source when resources are scarce. v. It can protect against dehydration. vi. It helps keep nutrients from moving out of the cell. 1. A capsule is a glycocalyx that is neatly organized and is firmly attached to the cell wall. a. Capsules prevent phagocytosis by the host’s immune system. 2. A slime layer is a glycocalyx that is unorganized and is loosely attached to the cell wall. b. Extracellular polysaccharide (extracellular polymeric substance) is a glycocalyx made of sugars and allows bacterial cells to attach to various surfaces.Prokaryotic Flagella. i. Long, semi-rigid, helical, cellular appendage used for locomotion. ii. Made of chains of the protein flagellin. 1. Attached to a protein hook. iii. Anchored to the cell wall and cell membrane by the basal body. iv. Motile Cells. 1. Rotate flagella to run and tumble. 2. Move toward or away from stimuli (taxis). a. Chemotaxis. b. Phototaxis. c. Axial Filaments (Endoflagella). i. In spirochetes: 1. Anchored at one end of a cell. 2. Covered by an outer sheath. 3. Rotation causes cell to move like a corkscrew through a cork. d. Fimbriae. i. Shorter, straighter, thinner than flagella. ii. Not used for locomotion. iii. Allow for the attachment of bacteria to surfaces. iv. Can be found at the poles of the cell, or covering the cell’s entire surface. v. There may be few or many fimbriae on a single bacterium. e. Pili (sex pili). i. Longer than fimbriae. ii. Only one or two per cell. iii. Are used to transfer DNA from one bacterial cell to another, and in twitching & gliding motility. IV. The Prokaryotic Cell Wall. a. Chemically and structurally complex, semi-rigid, gives structure to and protects the cell. b. Surrounds the underlying plasma membrane. 4 c. Prevents osmotic lysis. d. Contributes to the ability to cause disease in some species, and is the site of action for some antibiotics. e. Made of peptidoglycan (in bacteria). i. Polymer of a disaccharide. 1. N-acetylglucosamine (NAG) & N-acetylmuramic acid (NAM). ii. Disaccharides linked by polypeptides to form lattice surrounding the cell. Fig. iii. Penicillin inhibits this lattice formation, and leads to cellular lysis. f. Gram-positive cell walls. Fig. i. Many layers of peptidoglycan, resulting in a thick, rigid structure. ii. Teichoic acids. 1. May regulate movement of cations (+). 2. May be involved in cell growth, preventing extensive wall breakdown and lysis. 3. Contribute to antigenic specificity for each Gram-positive bacterial species. 4. Lipoteichoic acid links to plasma membrane. 5. Wall teichoic acid links to peptidoglycan. g. Gram-negative cell walls. i. Contains only one or a few layers of peptidoglycan. 1. Peptidoglycan is found in the periplasm, a fluid-filled space between the outer membrane and plasma membrane. a. Periplasm contains many digestive enzymes and transport proteins. ii. No teichoic acids are found in Gram-negative cell walls. iii. More susceptible to rupture than Gram-positive cells. iv. Outer membrane: 1. Composed of lipopolysaccharides, lipoproteins, and phospholipids. 2. Protects the cell from phagocytes, complement, antibiotics, lysozyme, detergents, heavy metals, bile salts, and certain dyes. 3. Contains transport proteins called porins. 4. Lipopolysaccharide is composed of: a. O polysaccharide (antigen) that can be used to ID certain Gram- negative bacterial species. b. Lipid A (endotoxin) can cause shock, fever, and even death if enough is released into the host’s blood. h. Gram Stain Mechanism. i. Crystal Violet-Iodine (CV-I) crystals form within the cell. ii. Gram-positive: 1. Alcohol dehydrates peptidoglycan. 2. CV-I crystals cannot leave. iii. Gram-negative: 1. Alcohol dissolves outer membrane and leaves holes in peptidoglycan. 2. CV-I washes out. 3. Safranin stains the cell pink. iv. Table 1, pg. 94, compares Gram-positive and Gram-negative bacteria. i. Damage to Prokaryotic Cell Walls. i. Because prokaryotic cell walls contain substances not normally found in animal 5 cells, drugs or chemicals that disrupt prokaryotic cell wall structures are often used in medicine, or by the host to combat the bacteria. 1. Lysozyme digests the disaccharides in peptidoglycan. 2. Penicillin inhibits the formation of peptide bridges in peptidoglycan. ii. A protoplast is a Gram-positive cell whose cell wall has been destroyed, but that is still alive and functional. (Lost its peptidoglycan). iii. A spheroplast is a wall-less Gram-negative cell. (Lost its outer membrane and peptidoglycan). iv. L forms are wall-less cells that swell into irregular shapes. They can live, divide, and may return to a walled state. v. Protoplasts and spheroplasts are susceptible to osmotic lysis. vi. Gram-negative bacteria are not as susceptible to penicillin due to the outer membrane and the small amount of peptidoglycan in their walls. vii. Gram-negative bacteria are susceptible to antibiotics that can penetrate the outer membrane (Streptomycin, chloramphenicol, tetracycline). V. Structures Internal to the Cell Wall. a. Plasma Membrane (Inner Membrane). a. Phospholipid bilayer lying inside the cell wall. 1. The phospholipid bilayer is the basic framework of the plasma membrane. 2. The bilayer arrangement occurs because the phospholipids are amphipathic molecules. They have both polar (charged) and nonpolar (uncharged) parts with the polar “head” of the phospholipid pointing out and the nonpolar “tails” pointing toward the center of the membrane, forming a nonpolar, hydrophobic region in the membrane’s interior. b. Much of the metabolic machinery is located on the plasma membrane. Photosynthesis, aerobic cellular respiration, and anaerobic cellular respiration reactions occur here. This means that there is a surface area to volume ratio at which bacteria reach a critical size threshold, beyond which bacteria can’t survive. i. Thiomargarita (0.75 mm) is the largest known bacterium and is larger than most eukaryotic cells. It has many invaginations of the plasma membrane, which increases it surface area relative to its volume. c. Peripheral proteins. i. Enzymes. ii. Structural proteins. iii. Some assist the cell in changing membrane shape. d. Integral proteins and transmembrane proteins. i. Provide channels for movement of materials into and out of the cell. e. Fluid Mosaic Model. i. Membrane is as viscous as olive oil. ii. Proteins move to function. iii. Phospholipids rotate and move laterally. f. Selective permeability allows the passage of some molecules but not others across the plasma membrane. i. Large molecules cannot pass through. ii. Ions pass through very slowly or not at all. iii. Lipid soluble molecules pass through easily. iv.Smaller molecules (water, oxygen, carbon dioxide, some simple sugars) 6 usually pass through easily. g. The plasma membrane contains enzymes for ATP production. h. Photosynthetic pigments are found on in-foldings of the plasma membrane called chromatophores or thylakoids. Fig. 15. i. Damage to the plasma membrane by alcohols, quaternary ammonium compounds (a class of disinfectants) and polymyxin antibiotics causes leakage of cell contents. j. Movement of Materials Across Membranes. 1. Passive Processes: a. Simple diffusion: Movement of a solute from an area of high concentration to an area of low concentration (down its concentration gradient) until equilibrium is reached. b. Facilitated diffusion: Solute combines with a transport protein in the membrane, to pass from one side of the membrane to the other. The molecule is still moving down its concentration gradient. The transport proteins are specific. c. Osmosis. i. Movement of water across a selectively permeable membrane from an area of higher water concentration to an area of lower water concentration. ii. Osmotic pressure. The pressure needed to stop the movement of water across the membrane. iii. Isotonic, hypotonic, and hypertonic solutions. 2. Active Processes: a. Active transport of substances requires a transporter protein and ATP. The solute molecule is pumped against its concentration gradient. Transport proteins are specific. i. In group translocation (a special form of active transport found only in prokaryotes) movement of a substance requires a specific transport protein. 1. The substance is chemically altered during transport, preventing it from escaping the cell after it is transported inside. 2. This process requires high-energy phosphate compounds like phosphoenolpyruvic acid (PEP) to phosphorylate the transported molecule, preventing its movement out of the cell. b. Cytoplasm. i. Cytoplasm is the substance inside the plasma membrane. ii. It is about 80% water. iii. Contains proteins, enzymes, carbohydrates, lipids, inorganic ions, various compounds, a nuclear area, ribosomes, and inclusions. c. Nuclear Area (Nucleoid). i. Contains a single circular chromosome made of DNA. 1. No histones or introns in bacteria. 2. The chromosome is attached to the plasma membrane at a point along its length, where proteins synthesize and partition new DNA for division during binary fission. ii. Is not surrounded by a nuclear envelope the way eukaryotic chromosomes are. iii. Also contains small circular DNA molecules called plasmids. 1. Plasmids can be gained or lost without harming the cell. 2. Usually contain less than 100 genes. 3. Can be beneficial if they contain genes for antibiotic resistance, tolerance to toxic metals, production of toxins, or synthesis of enzymes. 4. They can be transferred from one bacterium to another. 7 5. Plasmids are used in genetic engineering. d. Ribosomes. i. Site of protein synthesis. ii. Composed of a large and small subunit, both made of protein and rRNA. iii. Prokaryotic ribosomes are 70S ribosomes. 1. Made of a small 30S subunit and a larger 50S subunit. iv. Eukaryotic ribosomes are 80S ribosomes. 1. Made of a small 40S subunit and a larger 60S subunit. v. Certain antibiotics target only prokaryotic ribosomal subunits without targeting eukaryotic ribosomal subunits. e. Inclusions. i. Reserve deposits of nutrients that can be used in times of low resource availability. ii. Include: 1. Metachromatic granules (volutin). Reserve of inorganic phosphate for ATP. 2. Polysaccharide granules. Glycogen and starch. 3. Lipid inclusions. 4. Sulfur granules. Energy reserve for “sulfur bacteria” that derive energy by oxidizing sulfur and sulfur compounds. 5. Carboxysomes. Contain an enzyme necessary for bacteria that use carbon dioxide as their only source of carbon for carbon dioxide fixation. 6. Gas vacuoles. Help bacteria maintain buoyancy. 7. Magnetosomes. Made of iron oxide, they serve as ballast to help some bacteria sink until reaching an appropriate attachment site. They also decompose hydrogen peroxide. f. Endospores. i. Resting Gram-positive bacterial cells that form when essential nutrients can no longer be obtained. ii. Resistant to desiccation, heat, chemicals, radiation. iii. Bacillus anthracis (anthrax), Clostridium spp. (gangrene, tetanus, botulism, food poisoning). iv. Sporulation (sporogenesis): the process of endospore formation within the vegetative (functional) cell. This takes several hours. 1. Spore septum (invagination of plasma membrane) begins to isolate the newly replicated DNA and a small portion of cytoplasm. This results in the formation of two separate membrane bound structures. 2. The plasma membrane starts to surround the DNA, cytoplasm, and the new membrane encircling the material isolated in step 1, forming a double-layered membrane-bound structure called a forespore. 3. Thick peptidoglycan layers are laid down between the two membranes of the forespore. 4. Then a thick spore coat of protein forms around the outer membrane of the forespore, which is responsible for the durability of the endospore. 5. When the endospore matures, the vegetative cell wall ruptures, killing the cell, and freeing the endospore. a. The endospore is metabolically inert, and contains the chromosome, 8 some RNA, ribosomes, enzymes, other molecules, and very little water. b. Endospores can remain dormant for millions of years. v. Germination: the return to the vegetative state. 1. Triggered by damage to the endospore coat. The enzymes activate, breaking down the protective layers. Water then can enter, and metabolism resumes. vi. Endospores can survive conditions that vegetative cells cannot: boiling, freezing, desiccation, chemical exposure, radiation, etc. EUKARYOTES: a. Make up algae, protozoa, fungi, higher plants, and animals. Flagella and Cilia. Rotate Cilia are numerous, short, hair-like projections extending from the surface of a cell. They function to move materials across the surface of the cell, or move the cell around in its environment. i. Flagella are similar to cilia but are much longer, usually moving an entire cell. The only example of a flagellum in the human body is the sperm cell tail. 1. Eukaryotic flagella move in a whip-like manner, while prokaryotic flagella 9 b. Cell Wall. i. Simple compared to prokaryotes. 1. No peptidoglycan in eukaryotes. a. Antibiotics that target peptidoglycan (penicillins and cephalosporins) do not harm us. ii. Cell walls are found in plants, algae, and fungi. iii. Made of carbohydrates. 1. Cellulose in algae, plants, and some fungi. 2. Chitin in most fungi. 3. Glucan and mannan in yeasts (unicellular fungi). c. Glycocalyx. i. Sticky carbohydrates extending from an animal cell’s plasma membrane. ii. Glycoproteins and glycolipids form a sugary coat around the cell—the glycocalyx— which helps cells recognize one another, adhere to one another in some tissues, and protects the cell from digestion by enzymes in the extracellular fluid. 1. The glycocalyx also attracts a film of fluid to the surface of many cells, such as RBC’s, making them slippery so they can pass through narrow vessels. d. Plasma Membrane. i. The plasma membrane is a flexible, sturdy barrier that surrounds and contains the cytoplasm of the cell. 1. The fluid mosaic model describes its structure. 2. The membrane consists of proteins in a sea of phospholipids. a. Some proteins float freely while others are anchored at specific locations. b. The membrane lipids allow passage of several types of lipid-soluble molecules but act as a barrier to the passage of charged or polar substances. c. Channel and transport proteins allow movement of polar molecules and ions across the membrane. ii. Phospholipid bilayer. 1. Has the same basic arrangement as the prokaryotic plasma membrane. iii. Arrangement of Membrane Proteins. 1. The membrane proteins are divided into integral and peripheral proteins. a. Integral proteins extend into or across the entire lipid bilayer among the fatty acid tails of the phospholipid molecules, and are firmly anchored in place. i. Most are transmembrane proteins, which span the entire lipid bilayer and protrude into both the cytosol and extracellular fluid. b. Peripheral proteins associate loosely with the polar heads of membrane lipids, and are found at the inner or outer surface of the membrane. 10 2. Many membrane proteins are glycoproteins (proteins with carbohydrate groups attached to the ends that protrude into the extracellular fluid). iv. Functions of Membrane Proteins. 1. Membrane proteins vary in different cells and function as: a. Ion channels (pores): Allow ions such as sodium or potassium to cross the cell membrane; (they can't diffuse through the bilayer). Most are selective—they allow only a single type of ion to pass. Some ion channels open and close. b. Transporters: selectively move a polar substance from one side of the membrane to the other. c. Receptors: recognize and bind a specific molecule. The chemical binding to the receptor is called a ligand. d. Enzymes: catalyze specific chemical reactions at the inside or outside surface of the cell. e. Cell-identity markers (often glycoproteins and glycolipids), such as human leukocyte antigens. f. Linkers: anchor proteins in the plasma membrane of neighboring cells to each other or to protein filaments inside and outside the cell. 2. The different proteins help to determine many of the functions of the plasma membrane. v. Selective permeability of the plasma membrane allows passage of some molecules. 1. Transport mechanisms: a. Simple diffusion. b. Facilitated diffusion. c. Osmosis. d. Active transport. (No group translocation in Eukaryotes). e. Vesicular Transport. i. A vesicle is a small membranous sac formed by budding off from an existing membrane. ii. Two types of vesicular transport are endocytosis and exocytosis. 1. Endocytosis. a. In endocytosis, materials move into a cell in a vesicle formed from the plasma membrane. b. Viruses can take advantage of this mechanism to enter cells. c. Phagocytosis is the ingestion of solid particles, such as worn out cells, bacteria, or viruses. Pseudopods extend and engulf particles. d. Pinocytosis is the ingestion of extracellular fluid. The membrane folds inward bringing in fluid and dissolved substances. 2. In exocytosis, membrane-enclosed structures called secretory vesicles that form inside the cell fuse with the plasma membrane and release their contents into the extracellular fluid. f. Cytoplasm. i. Substance inside the plasma membrane and outside nucleus. ii. Cytosol is the fluid portion of cytoplasm. iii. Cytoskeleton. 1. The cytoskeleton is a network of several kinds of protein filaments that extend throughout the cytoplasm, and provides a structural framework for the cell. 2. It consists of microfilaments, intermediate filaments, and microtubules. 11 a. Most microfilaments (the smallest cytoskeletal elements) are composed of actin and function in movement (muscle contraction and cell division) and mechanical support for the cell itself and for microvilli. b. Intermediate filaments are composed of several different proteins and function in support and to help anchor organelles such as the nucleus. c. Microtubules (the largest cytoskeletal elements) are composed of a protein called tubulin and help determine cell shape; they function in the intracellular transport of organelles and the migration of chromosome during cell division. They also function in the movement of cilia and flagella. iv. Cytoplasmic streaming. 1. Movement of cytoplasm and nutrients throughout cells. 2. Moves the cell over surfaces. g. Organelles. i. Organelles are specialized structures that have characteristic shapes and perform specific functions in eukaryotic cellular growth, maintenance, reproduction. 2.1.RIBOSOMES. Nucleus. The nucleus is usually the most prominent feature of a eukaryotic cell. b. Most have a single nucleus; some cells (human red blood cells) have none, whereas others (human skeletal muscle fibers) have several in each cell. c. The parts of the nucleus include the: i. Nuclear envelope (a double membrane), which is perforated by channels called nuclear pores, that control the movement of substances between the nucleus and the cytoplasm. 1. Small molecules and ions diffuse passively, while movement of most large molecules out of the nucleus involves active transport. ii. Nucleoli function in producing ribosomes. d. Genetic material (DNA). Within the nucleus are the cell’s hereditary units, called genes, which are arranged in single file along chromosomes. Each chromosome is a long molecule of DNA that is coiled together with several proteins (including histones). a. Sites of protein synthesis. b. 80S in eukaryotes. i. Membrane-bound ribosomes found on rough ER. ii. Free ribosomes found in cytoplasm. c. 70S in prokaryotes. i. Also found in chloroplasts and mitochondria. 3. Endoplasmic Reticulum. a. The endoplasmic reticulum (ER) is a network of membranes extending from the nuclear membrane that form flattened sacs or tubules. b. Rough ER is continuous with the nuclear membrane and has its outer surface studded with ribosomes, which synthesize proteins. The proteins then enter the space inside the ER for processing (into glycoproteins or for attachment to phospholipids) and sorting, 12 and are then either incorporated into organelle membranes, inserted into the plasma membrane, or secreted via exocytosis. c. Smooth ER extends from the rough ER to form a network of membrane tubules, but it does not contain ribosomes on its membrane surface. In humans, it synthesizes fatty acids and steroids, detoxifies drugs, removes phosphate from glucose 6-phosphate (allowing free glucose to enter the blood), and stores and releases calcium ions involved in muscle contraction. 4. Golgi Complex. The Golgi complex consists of four to six stacked, flattened membranous sacs (cisterns). The cis (entry) face faces the rough ER, and trans (exit) face faces the cell’s plasma membrane. Between the cis and trans faces are the medial cisternae. b. The cis, medial, and trans cisternae each contain different enzymes that permit each to modify, sort, and package proteins received from the rough ER for transport to different destinations (such as the plasma membrane, to other organelles, or for export out of the cell). 5. Lysosomes. a. Lysosomes are membrane-enclosed vesicles that form from the Golgi complex and contain powerful digestive enzymes. b. Lysosomes function in digestion of substances that enter the cell by endocytosis, and transport the final products of digestion into the cytosol. c. They digest worn-out organelles (autophagy). d. They digest their own cellular contents (autolysis). e. They carry out extracellular digestion (as happens when sperm release lysosomal enzymes to aid in penetrating an oocyte). 6. Vacuoles. a. Space in the cytoplasm enclosed by a membrane called a tonoplast. b. Derived from the Golgi complex. c. They serve in the following ways: i. Temporary storage for biological molecules and ions. ii. Bring food into cells. iii. Provide structural support. iv. Store metabolic wastes. 7. Peroxisomes. a. Peroxisomes are similar in structure to lysosomes, but are smaller. b. They contain enzymes (oxidases) that use molecular oxygen to oxidize (remove hydrogen atoms from) various organic substances. 13 c. They take part in normal metabolic reactions such as the oxidation of amino and fatty acids. d. New peroxisomes form by budding off from preexisting ones. e. They produce and then destroy H2O2 (hydrogen peroxide) in the process of their metabolic activities. 8. Centrosomes. a. Centrosomes are dense areas of cytoplasm containing the centrioles, which are paired cylinders arranged at right angles to one another, and serve as centers for organizing microtubules and the mitotic spindle during mitosis. 9. Mitochondria. a. Found in nearly all eukaryotic cells. b. A mitochondrion is bound by a double membrane, with a fluid-filled space between called the intermembranous space. The outer membrane is smooth, while the inner membrane is arranged in folds called cristae. The mitochondrial matrix is found inside the inner mitochondrial membrane. c. The folds of the cristae provide a large surface area for the chemical reactions that are part of the aerobic phase of cellular respiration. These reactions produce most of a eukaryotic cell’s ATP, and the enzymes that catalyze them are located on the cristae and in the matrix. d. Mitochondria self-replicate using their own DNA and contain 70S ribosomes. They grow and reproduce on their own in a way that is similar to binary fission. Mitochondrial DNA (genes) is inherited only from the mother, since sperm normally lack most organelles such as mitochondria, ribosomes, ER, and the Golgi complex. Any sperm mitochondria that do enter the oocyte are soon destroyed. 10. Chloroplasts. a. Found only in algae and green plants. b. Contain the pigment chlorophyll and enzymes necessary for photosynthesis. c. Chloroplasts self-replicate using their own DNA and contain 70S ribosomes. They grow and reproduce on their own in a way that is similar to binary fission. VII. Endosymbiotic Theory. a. Large bacterial cells lost their cell walls and engulfed smaller bacteria. b. A symbiotic (mutualistic) relationship developed. i. The host cell supplied the nutrients. ii. The engulfed cell produced excess energy that the host could use. iii. The relationship evolved. c. Evidence: 14 i. Mitochondria and chloroplasts resemble bacteria in size and shape. 1. They divide on their own—independently of the host, and contain their own DNA (single circular chromosome). This process is nearly identical to binary fission seen in bacteria. 2. They contain 70S ribosomes. 3. Their method of protein synthesis is more like that of prokaryotes (no RNA processing). 4. Antibiotics that inhibit protein synthesis on ribosomes in bacteria also inhibit protein Difference among eukaryotic cells There are many different types of eukaryotic cells, though animals and plants are the most familiar eukaryotes, and thus provide an excellent starting point for understanding eukaryotic structure. Fungi and many protists have some substantial differences, however. Animal cell An animal cell is a form of eukaryotic cell that makes up many tissues in animals. Animal cells are distinct from other eukaryotes, most notably plant cells, as they lack cell walls and chloroplasts. They also have smaller vacuoles. Due to the lack of a cell wall, animal cells can adopt a variety of shapes. A phagocytic cell can even engulf other structures. There are many different types of cell. For instance, there are approximately 210 distinct cell types in the adult human body. Plant cell Plant cells are quite different from the cells of the other eukaryotic organisms. Their distinctive features are: A large central vacuole (enclosed by a membrane, the tonoplast), which maintains the cell's turgor and controls movement ofmolecules between the cytosol and sap A primary cell wall containing cellulose, hemicellulose and pectin, deposited by the protoplast on the outside of the cell membrane; this contrasts with the cell walls of fungi, which contain chitin, and the cell envelopes of prokaryotes, in which peptidoglycans are the main structural molecules The plasmodesmata, linking pores in the cell wall that allow each plant cell to communicate with other adjacent cells; this is different from the functionally analogous system of gap junctions between animal cells. 15 Plastids, especially chloroplasts that contain chlorophyll, the pigment that gives plants their green color and allows them to perform photosynthesis Bryophytes and seedless vascular plants lack flagellae and centrioles except in the sperm cells.[16] Sperm of cycads and Ginkgoare large, complex cells that swim with hundreds to thousands of flagellae. Conifers (Pinophyta) and flowering plants (Angiospermae) lack the flagellae and centrioles that are present in animal cells.

You can only respond using information from the context provided. Arrange the answers in numbered list with headers. What are the differences between the types of cells described and some life forms they make up. CELL STRUCTURE Cells are the building blocks of life. A cell is chemical system that is able to maintain its structure and reproduce. Cells are the fundamental unit of life. All living things are cells or composed of cells. Although different living things may be as unlike as a violet and an octopus, they are all built in essentially the same way. The most basic similarity is that all living things are composed of one or more cells. This is known as the Cell Theory. Our knowledge of cells is built on work done with microscopes. English scientist Robert Hooke in 1665 first described cells from his observations of cork slices. Hooke first used the word "cell". Dutch amateur scientist Antonie van Leeuwenhoek discovered microscopic animals in water. German scientists Schleiden and Schwann in 1830's were first to say that all organisms are made of one or more cells. German biologist Virchow in 1858 stated that all cells come from the division of pre-existing cells. The Cell Theory can be summarized as: Cells are the fundamental unit of life - nothing less than a cell is alive. All organisms are constructed of and by cells. All cells arise from preexisting cells. Cells contain the information necessary for their own reproduction. No new cells are originating spontaneously on earth today. Cells are the functional units of life. All biochemical processes are carried out by cells. • Groups of cells can be organized and function as multicellular organisms Cells of multicellular organisms can become specialized in form and function to carry out subprocesses of the multicellular organism. Cells are common to all living beings, and provide information about all forms of life. Because all cells come from existing cells, scientists can study cells to learn about growth, reproduction, and all other functions that living things perform. By learning about cells and how they function, we can learn about all types of living things. Classification of cells: All living organisms (bacteria, blue green algae, plants and animals) have cellular organization and may contain one or many cells. The organisms with only one cell in their body are called unicellular organisms (bacteria, blue green algae, some algae, Protozoa, etc.). The organisms having many cells in their body are called multicellular organisms (fungi, most plants and animals). Any living organism may contain only one type of cell either A. Prokaryotic cells; B. Eukaryotic cells. The terms prokaryotic and eukaryotic were suggested by Hans Ris in the 1960’s. This classification is based on their complexity. Further based on the kingdom into which they may fall i.e the plant or the animal kingdom, plant and animal cells bear many differences. These will be studied in detail in the upcoming sections PROKARYOTIC CELLS Prokaryote comes from the Greek words for pre-nucleus. Prokaryotes: i. One circular chromosome, not contained in a membrane. ii. No histones or introns are present in Bacteria; both are found in Eukaryotes and Archaea. iii. No membrane-bound organelles. (Only contain non membrane-bound organelles). iv. Bacteria contain peptidoglycan in cell walls; Eukaryotes and Archaea do not. v. Binary fission. 2 Size, Shape, and Arrangement of Bacterial Cells. i. Average size of prokaryotic cells: 0.2 -2.0 μm in diameter 1-10 μm (0.001 – 0.01 mm) [book says 2 – 8 μm] in length. 1. Typical eukaryote 10-500 μm in length (0.01 – 0.5 mm). 2. Typical virus 20-1000 nm in length (0.00000002 – 0.000001 m). 3. Thiomargarita is the largest bacterium known. It is about the size of a typed period (0.75 mm). 4. Nanoarchaeum is the smallest cell known. It is at the lower theoretical limit for cell size (0.4 μm). ii. Basic bacterial shapes: 1. Coccus (sphere/round). 2. Bacillus (staff/rod-shaped). 3. Spirilla (rigid with a spiral/corkscrew shape). a. Flagella propel these bacteria. 4. Vibrio (curved rod). 5. Spirochetes (flexible with a spiral shape). Axial filaments (endoflagella) propel these bacteria. iii. Descriptive prefixes: 1. Diplo (two cells). 2. Tetra (four cells). 3. Sarcinae (cube of 8 cells). 4. Staphylo (clusters of cells). 5. Strepto (chains of cells). iv. Unusual bacterial shapes: 1. Star-shaped Stella. 2. Square/rectangular Haloarcula. v. Arrangements: 1. Pairs: diplococci, diplobacilli 2. Clusters: staphylococci 3. Chains: streptococci, streptobacilli. vi. Most bacteria are monomorphic. They do not change shape unless environmental conditions change. vii. A few are pleomorphic. These species have individuals that can come in a variety of shapes Structures External to the Prokaryotic Cell Wall. a. Glycocalyx (sugar coat). i. Usually very sticky. ii. Found external to cell wall. iii. Composed of polysaccharide and/or polypeptide. iv. It can be broken down and used as an energy source when resources are scarce. v. It can protect against dehydration. vi. It helps keep nutrients from moving out of the cell. 1. A capsule is a glycocalyx that is neatly organized and is firmly attached to the cell wall. a. Capsules prevent phagocytosis by the host’s immune system. 2. A slime layer is a glycocalyx that is unorganized and is loosely attached to the cell wall. b. Extracellular polysaccharide (extracellular polymeric substance) is a glycocalyx made of sugars and allows bacterial cells to attach to various surfaces.Prokaryotic Flagella. i. Long, semi-rigid, helical, cellular appendage used for locomotion. ii. Made of chains of the protein flagellin. 1. Attached to a protein hook. iii. Anchored to the cell wall and cell membrane by the basal body. iv. Motile Cells. 1. Rotate flagella to run and tumble. 2. Move toward or away from stimuli (taxis). a. Chemotaxis. b. Phototaxis. c. Axial Filaments (Endoflagella). i. In spirochetes: 1. Anchored at one end of a cell. 2. Covered by an outer sheath. 3. Rotation causes cell to move like a corkscrew through a cork. d. Fimbriae. i. Shorter, straighter, thinner than flagella. ii. Not used for locomotion. iii. Allow for the attachment of bacteria to surfaces. iv. Can be found at the poles of the cell, or covering the cell’s entire surface. v. There may be few or many fimbriae on a single bacterium. e. Pili (sex pili). i. Longer than fimbriae. ii. Only one or two per cell. iii. Are used to transfer DNA from one bacterial cell to another, and in twitching & gliding motility. IV. The Prokaryotic Cell Wall. a. Chemically and structurally complex, semi-rigid, gives structure to and protects the cell. b. Surrounds the underlying plasma membrane. 4 c. Prevents osmotic lysis. d. Contributes to the ability to cause disease in some species, and is the site of action for some antibiotics. e. Made of peptidoglycan (in bacteria). i. Polymer of a disaccharide. 1. N-acetylglucosamine (NAG) & N-acetylmuramic acid (NAM). ii. Disaccharides linked by polypeptides to form lattice surrounding the cell. Fig. iii. Penicillin inhibits this lattice formation, and leads to cellular lysis. f. Gram-positive cell walls. Fig. i. Many layers of peptidoglycan, resulting in a thick, rigid structure. ii. Teichoic acids. 1. May regulate movement of cations (+). 2. May be involved in cell growth, preventing extensive wall breakdown and lysis. 3. Contribute to antigenic specificity for each Gram-positive bacterial species. 4. Lipoteichoic acid links to plasma membrane. 5. Wall teichoic acid links to peptidoglycan. g. Gram-negative cell walls. i. Contains only one or a few layers of peptidoglycan. 1. Peptidoglycan is found in the periplasm, a fluid-filled space between the outer membrane and plasma membrane. a. Periplasm contains many digestive enzymes and transport proteins. ii. No teichoic acids are found in Gram-negative cell walls. iii. More susceptible to rupture than Gram-positive cells. iv. Outer membrane: 1. Composed of lipopolysaccharides, lipoproteins, and phospholipids. 2. Protects the cell from phagocytes, complement, antibiotics, lysozyme, detergents, heavy metals, bile salts, and certain dyes. 3. Contains transport proteins called porins. 4. Lipopolysaccharide is composed of: a. O polysaccharide (antigen) that can be used to ID certain Gram- negative bacterial species. b. Lipid A (endotoxin) can cause shock, fever, and even death if enough is released into the host’s blood. h. Gram Stain Mechanism. i. Crystal Violet-Iodine (CV-I) crystals form within the cell. ii. Gram-positive: 1. Alcohol dehydrates peptidoglycan. 2. CV-I crystals cannot leave. iii. Gram-negative: 1. Alcohol dissolves outer membrane and leaves holes in peptidoglycan. 2. CV-I washes out. 3. Safranin stains the cell pink. iv. Table 1, pg. 94, compares Gram-positive and Gram-negative bacteria. i. Damage to Prokaryotic Cell Walls. i. Because prokaryotic cell walls contain substances not normally found in animal 5 cells, drugs or chemicals that disrupt prokaryotic cell wall structures are often used in medicine, or by the host to combat the bacteria. 1. Lysozyme digests the disaccharides in peptidoglycan. 2. Penicillin inhibits the formation of peptide bridges in peptidoglycan. ii. A protoplast is a Gram-positive cell whose cell wall has been destroyed, but that is still alive and functional. (Lost its peptidoglycan). iii. A spheroplast is a wall-less Gram-negative cell. (Lost its outer membrane and peptidoglycan). iv. L forms are wall-less cells that swell into irregular shapes. They can live, divide, and may return to a walled state. v. Protoplasts and spheroplasts are susceptible to osmotic lysis. vi. Gram-negative bacteria are not as susceptible to penicillin due to the outer membrane and the small amount of peptidoglycan in their walls. vii. Gram-negative bacteria are susceptible to antibiotics that can penetrate the outer membrane (Streptomycin, chloramphenicol, tetracycline). V. Structures Internal to the Cell Wall. a. Plasma Membrane (Inner Membrane). a. Phospholipid bilayer lying inside the cell wall. 1. The phospholipid bilayer is the basic framework of the plasma membrane. 2. The bilayer arrangement occurs because the phospholipids are amphipathic molecules. They have both polar (charged) and nonpolar (uncharged) parts with the polar “head” of the phospholipid pointing out and the nonpolar “tails” pointing toward the center of the membrane, forming a nonpolar, hydrophobic region in the membrane’s interior. b. Much of the metabolic machinery is located on the plasma membrane. Photosynthesis, aerobic cellular respiration, and anaerobic cellular respiration reactions occur here. This means that there is a surface area to volume ratio at which bacteria reach a critical size threshold, beyond which bacteria can’t survive. i. Thiomargarita (0.75 mm) is the largest known bacterium and is larger than most eukaryotic cells. It has many invaginations of the plasma membrane, which increases it surface area relative to its volume. c. Peripheral proteins. i. Enzymes. ii. Structural proteins. iii. Some assist the cell in changing membrane shape. d. Integral proteins and transmembrane proteins. i. Provide channels for movement of materials into and out of the cell. e. Fluid Mosaic Model. i. Membrane is as viscous as olive oil. ii. Proteins move to function. iii. Phospholipids rotate and move laterally. f. Selective permeability allows the passage of some molecules but not others across the plasma membrane. i. Large molecules cannot pass through. ii. Ions pass through very slowly or not at all. iii. Lipid soluble molecules pass through easily. iv.Smaller molecules (water, oxygen, carbon dioxide, some simple sugars) 6 usually pass through easily. g. The plasma membrane contains enzymes for ATP production. h. Photosynthetic pigments are found on in-foldings of the plasma membrane called chromatophores or thylakoids. Fig. 15. i. Damage to the plasma membrane by alcohols, quaternary ammonium compounds (a class of disinfectants) and polymyxin antibiotics causes leakage of cell contents. j. Movement of Materials Across Membranes. 1. Passive Processes: a. Simple diffusion: Movement of a solute from an area of high concentration to an area of low concentration (down its concentration gradient) until equilibrium is reached. b. Facilitated diffusion: Solute combines with a transport protein in the membrane, to pass from one side of the membrane to the other. The molecule is still moving down its concentration gradient. The transport proteins are specific. c. Osmosis. i. Movement of water across a selectively permeable membrane from an area of higher water concentration to an area of lower water concentration. ii. Osmotic pressure. The pressure needed to stop the movement of water across the membrane. iii. Isotonic, hypotonic, and hypertonic solutions. 2. Active Processes: a. Active transport of substances requires a transporter protein and ATP. The solute molecule is pumped against its concentration gradient. Transport proteins are specific. i. In group translocation (a special form of active transport found only in prokaryotes) movement of a substance requires a specific transport protein. 1. The substance is chemically altered during transport, preventing it from escaping the cell after it is transported inside. 2. This process requires high-energy phosphate compounds like phosphoenolpyruvic acid (PEP) to phosphorylate the transported molecule, preventing its movement out of the cell. b. Cytoplasm. i. Cytoplasm is the substance inside the plasma membrane. ii. It is about 80% water. iii. Contains proteins, enzymes, carbohydrates, lipids, inorganic ions, various compounds, a nuclear area, ribosomes, and inclusions. c. Nuclear Area (Nucleoid). i. Contains a single circular chromosome made of DNA. 1. No histones or introns in bacteria. 2. The chromosome is attached to the plasma membrane at a point along its length, where proteins synthesize and partition new DNA for division during binary fission. ii. Is not surrounded by a nuclear envelope the way eukaryotic chromosomes are. iii. Also contains small circular DNA molecules called plasmids. 1. Plasmids can be gained or lost without harming the cell. 2. Usually contain less than 100 genes. 3. Can be beneficial if they contain genes for antibiotic resistance, tolerance to toxic metals, production of toxins, or synthesis of enzymes. 4. They can be transferred from one bacterium to another. 7 5. Plasmids are used in genetic engineering. d. Ribosomes. i. Site of protein synthesis. ii. Composed of a large and small subunit, both made of protein and rRNA. iii. Prokaryotic ribosomes are 70S ribosomes. 1. Made of a small 30S subunit and a larger 50S subunit. iv. Eukaryotic ribosomes are 80S ribosomes. 1. Made of a small 40S subunit and a larger 60S subunit. v. Certain antibiotics target only prokaryotic ribosomal subunits without targeting eukaryotic ribosomal subunits. e. Inclusions. i. Reserve deposits of nutrients that can be used in times of low resource availability. ii. Include: 1. Metachromatic granules (volutin). Reserve of inorganic phosphate for ATP. 2. Polysaccharide granules. Glycogen and starch. 3. Lipid inclusions. 4. Sulfur granules. Energy reserve for “sulfur bacteria” that derive energy by oxidizing sulfur and sulfur compounds. 5. Carboxysomes. Contain an enzyme necessary for bacteria that use carbon dioxide as their only source of carbon for carbon dioxide fixation. 6. Gas vacuoles. Help bacteria maintain buoyancy. 7. Magnetosomes. Made of iron oxide, they serve as ballast to help some bacteria sink until reaching an appropriate attachment site. They also decompose hydrogen peroxide. f. Endospores. i. Resting Gram-positive bacterial cells that form when essential nutrients can no longer be obtained. ii. Resistant to desiccation, heat, chemicals, radiation. iii. Bacillus anthracis (anthrax), Clostridium spp. (gangrene, tetanus, botulism, food poisoning). iv. Sporulation (sporogenesis): the process of endospore formation within the vegetative (functional) cell. This takes several hours. 1. Spore septum (invagination of plasma membrane) begins to isolate the newly replicated DNA and a small portion of cytoplasm. This results in the formation of two separate membrane bound structures. 2. The plasma membrane starts to surround the DNA, cytoplasm, and the new membrane encircling the material isolated in step 1, forming a double-layered membrane-bound structure called a forespore. 3. Thick peptidoglycan layers are laid down between the two membranes of the forespore. 4. Then a thick spore coat of protein forms around the outer membrane of the forespore, which is responsible for the durability of the endospore. 5. When the endospore matures, the vegetative cell wall ruptures, killing the cell, and freeing the endospore. a. The endospore is metabolically inert, and contains the chromosome, 8 some RNA, ribosomes, enzymes, other molecules, and very little water. b. Endospores can remain dormant for millions of years. v. Germination: the return to the vegetative state. 1. Triggered by damage to the endospore coat. The enzymes activate, breaking down the protective layers. Water then can enter, and metabolism resumes. vi. Endospores can survive conditions that vegetative cells cannot: boiling, freezing, desiccation, chemical exposure, radiation, etc. EUKARYOTES: a. Make up algae, protozoa, fungi, higher plants, and animals. Flagella and Cilia. Rotate Cilia are numerous, short, hair-like projections extending from the surface of a cell. They function to move materials across the surface of the cell, or move the cell around in its environment. i. Flagella are similar to cilia but are much longer, usually moving an entire cell. The only example of a flagellum in the human body is the sperm cell tail. 1. Eukaryotic flagella move in a whip-like manner, while prokaryotic flagella 9 b. Cell Wall. i. Simple compared to prokaryotes. 1. No peptidoglycan in eukaryotes. a. Antibiotics that target peptidoglycan (penicillins and cephalosporins) do not harm us. ii. Cell walls are found in plants, algae, and fungi. iii. Made of carbohydrates. 1. Cellulose in algae, plants, and some fungi. 2. Chitin in most fungi. 3. Glucan and mannan in yeasts (unicellular fungi). c. Glycocalyx. i. Sticky carbohydrates extending from an animal cell’s plasma membrane. ii. Glycoproteins and glycolipids form a sugary coat around the cell—the glycocalyx— which helps cells recognize one another, adhere to one another in some tissues, and protects the cell from digestion by enzymes in the extracellular fluid. 1. The glycocalyx also attracts a film of fluid to the surface of many cells, such as RBC’s, making them slippery so they can pass through narrow vessels. d. Plasma Membrane. i. The plasma membrane is a flexible, sturdy barrier that surrounds and contains the cytoplasm of the cell. 1. The fluid mosaic model describes its structure. 2. The membrane consists of proteins in a sea of phospholipids. a. Some proteins float freely while others are anchored at specific locations. b. The membrane lipids allow passage of several types of lipid-soluble molecules but act as a barrier to the passage of charged or polar substances. c. Channel and transport proteins allow movement of polar molecules and ions across the membrane. ii. Phospholipid bilayer. 1. Has the same basic arrangement as the prokaryotic plasma membrane. iii. Arrangement of Membrane Proteins. 1. The membrane proteins are divided into integral and peripheral proteins. a. Integral proteins extend into or across the entire lipid bilayer among the fatty acid tails of the phospholipid molecules, and are firmly anchored in place. i. Most are transmembrane proteins, which span the entire lipid bilayer and protrude into both the cytosol and extracellular fluid. b. Peripheral proteins associate loosely with the polar heads of membrane lipids, and are found at the inner or outer surface of the membrane. 10 2. Many membrane proteins are glycoproteins (proteins with carbohydrate groups attached to the ends that protrude into the extracellular fluid). iv. Functions of Membrane Proteins. 1. Membrane proteins vary in different cells and function as: a. Ion channels (pores): Allow ions such as sodium or potassium to cross the cell membrane; (they can't diffuse through the bilayer). Most are selective—they allow only a single type of ion to pass. Some ion channels open and close. b. Transporters: selectively move a polar substance from one side of the membrane to the other. c. Receptors: recognize and bind a specific molecule. The chemical binding to the receptor is called a ligand. d. Enzymes: catalyze specific chemical reactions at the inside or outside surface of the cell. e. Cell-identity markers (often glycoproteins and glycolipids), such as human leukocyte antigens. f. Linkers: anchor proteins in the plasma membrane of neighboring cells to each other or to protein filaments inside and outside the cell. 2. The different proteins help to determine many of the functions of the plasma membrane. v. Selective permeability of the plasma membrane allows passage of some molecules. 1. Transport mechanisms: a. Simple diffusion. b. Facilitated diffusion. c. Osmosis. d. Active transport. (No group translocation in Eukaryotes). e. Vesicular Transport. i. A vesicle is a small membranous sac formed by budding off from an existing membrane. ii. Two types of vesicular transport are endocytosis and exocytosis. 1. Endocytosis. a. In endocytosis, materials move into a cell in a vesicle formed from the plasma membrane. b. Viruses can take advantage of this mechanism to enter cells. c. Phagocytosis is the ingestion of solid particles, such as worn out cells, bacteria, or viruses. Pseudopods extend and engulf particles. d. Pinocytosis is the ingestion of extracellular fluid. The membrane folds inward bringing in fluid and dissolved substances. 2. In exocytosis, membrane-enclosed structures called secretory vesicles that form inside the cell fuse with the plasma membrane and release their contents into the extracellular fluid. f. Cytoplasm. i. Substance inside the plasma membrane and outside nucleus. ii. Cytosol is the fluid portion of cytoplasm. iii. Cytoskeleton. 1. The cytoskeleton is a network of several kinds of protein filaments that extend throughout the cytoplasm, and provides a structural framework for the cell. 2. It consists of microfilaments, intermediate filaments, and microtubules. 11 a. Most microfilaments (the smallest cytoskeletal elements) are composed of actin and function in movement (muscle contraction and cell division) and mechanical support for the cell itself and for microvilli. b. Intermediate filaments are composed of several different proteins and function in support and to help anchor organelles such as the nucleus. c. Microtubules (the largest cytoskeletal elements) are composed of a protein called tubulin and help determine cell shape; they function in the intracellular transport of organelles and the migration of chromosome during cell division. They also function in the movement of cilia and flagella. iv. Cytoplasmic streaming. 1. Movement of cytoplasm and nutrients throughout cells. 2. Moves the cell over surfaces. g. Organelles. i. Organelles are specialized structures that have characteristic shapes and perform specific functions in eukaryotic cellular growth, maintenance, reproduction. 2.1.RIBOSOMES. Nucleus. The nucleus is usually the most prominent feature of a eukaryotic cell. b. Most have a single nucleus; some cells (human red blood cells) have none, whereas others (human skeletal muscle fibers) have several in each cell. c. The parts of the nucleus include the: i. Nuclear envelope (a double membrane), which is perforated by channels called nuclear pores, that control the movement of substances between the nucleus and the cytoplasm. 1. Small molecules and ions diffuse passively, while movement of most large molecules out of the nucleus involves active transport. ii. Nucleoli function in producing ribosomes. d. Genetic material (DNA). Within the nucleus are the cell’s hereditary units, called genes, which are arranged in single file along chromosomes. Each chromosome is a long molecule of DNA that is coiled together with several proteins (including histones). a. Sites of protein synthesis. b. 80S in eukaryotes. i. Membrane-bound ribosomes found on rough ER. ii. Free ribosomes found in cytoplasm. c. 70S in prokaryotes. i. Also found in chloroplasts and mitochondria. 3. Endoplasmic Reticulum. a. The endoplasmic reticulum (ER) is a network of membranes extending from the nuclear membrane that form flattened sacs or tubules. b. Rough ER is continuous with the nuclear membrane and has its outer surface studded with ribosomes, which synthesize proteins. The proteins then enter the space inside the ER for processing (into glycoproteins or for attachment to phospholipids) and sorting, 12 and are then either incorporated into organelle membranes, inserted into the plasma membrane, or secreted via exocytosis. c. Smooth ER extends from the rough ER to form a network of membrane tubules, but it does not contain ribosomes on its membrane surface. In humans, it synthesizes fatty acids and steroids, detoxifies drugs, removes phosphate from glucose 6-phosphate (allowing free glucose to enter the blood), and stores and releases calcium ions involved in muscle contraction. 4. Golgi Complex. The Golgi complex consists of four to six stacked, flattened membranous sacs (cisterns). The cis (entry) face faces the rough ER, and trans (exit) face faces the cell’s plasma membrane. Between the cis and trans faces are the medial cisternae. b. The cis, medial, and trans cisternae each contain different enzymes that permit each to modify, sort, and package proteins received from the rough ER for transport to different destinations (such as the plasma membrane, to other organelles, or for export out of the cell). 5. Lysosomes. a. Lysosomes are membrane-enclosed vesicles that form from the Golgi complex and contain powerful digestive enzymes. b. Lysosomes function in digestion of substances that enter the cell by endocytosis, and transport the final products of digestion into the cytosol. c. They digest worn-out organelles (autophagy). d. They digest their own cellular contents (autolysis). e. They carry out extracellular digestion (as happens when sperm release lysosomal enzymes to aid in penetrating an oocyte). 6. Vacuoles. a. Space in the cytoplasm enclosed by a membrane called a tonoplast. b. Derived from the Golgi complex. c. They serve in the following ways: i. Temporary storage for biological molecules and ions. ii. Bring food into cells. iii. Provide structural support. iv. Store metabolic wastes. 7. Peroxisomes. a. Peroxisomes are similar in structure to lysosomes, but are smaller. b. They contain enzymes (oxidases) that use molecular oxygen to oxidize (remove hydrogen atoms from) various organic substances. 13 c. They take part in normal metabolic reactions such as the oxidation of amino and fatty acids. d. New peroxisomes form by budding off from preexisting ones. e. They produce and then destroy H2O2 (hydrogen peroxide) in the process of their metabolic activities. 8. Centrosomes. a. Centrosomes are dense areas of cytoplasm containing the centrioles, which are paired cylinders arranged at right angles to one another, and serve as centers for organizing microtubules and the mitotic spindle during mitosis. 9. Mitochondria. a. Found in nearly all eukaryotic cells. b. A mitochondrion is bound by a double membrane, with a fluid-filled space between called the intermembranous space. The outer membrane is smooth, while the inner membrane is arranged in folds called cristae. The mitochondrial matrix is found inside the inner mitochondrial membrane. c. The folds of the cristae provide a large surface area for the chemical reactions that are part of the aerobic phase of cellular respiration. These reactions produce most of a eukaryotic cell’s ATP, and the enzymes that catalyze them are located on the cristae and in the matrix. d. Mitochondria self-replicate using their own DNA and contain 70S ribosomes. They grow and reproduce on their own in a way that is similar to binary fission. Mitochondrial DNA (genes) is inherited only from the mother, since sperm normally lack most organelles such as mitochondria, ribosomes, ER, and the Golgi complex. Any sperm mitochondria that do enter the oocyte are soon destroyed. 10. Chloroplasts. a. Found only in algae and green plants. b. Contain the pigment chlorophyll and enzymes necessary for photosynthesis. c. Chloroplasts self-replicate using their own DNA and contain 70S ribosomes. They grow and reproduce on their own in a way that is similar to binary fission. VII. Endosymbiotic Theory. a. Large bacterial cells lost their cell walls and engulfed smaller bacteria. b. A symbiotic (mutualistic) relationship developed. i. The host cell supplied the nutrients. ii. The engulfed cell produced excess energy that the host could use. iii. The relationship evolved. c. Evidence: 14 i. Mitochondria and chloroplasts resemble bacteria in size and shape. 1. They divide on their own—independently of the host, and contain their own DNA (single circular chromosome). This process is nearly identical to binary fission seen in bacteria. 2. They contain 70S ribosomes. 3. Their method of protein synthesis is more like that of prokaryotes (no RNA processing). 4. Antibiotics that inhibit protein synthesis on ribosomes in bacteria also inhibit protein Difference among eukaryotic cells There are many different types of eukaryotic cells, though animals and plants are the most familiar eukaryotes, and thus provide an excellent starting point for understanding eukaryotic structure. Fungi and many protists have some substantial differences, however. Animal cell An animal cell is a form of eukaryotic cell that makes up many tissues in animals. Animal cells are distinct from other eukaryotes, most notably plant cells, as they lack cell walls and chloroplasts. They also have smaller vacuoles. Due to the lack of a cell wall, animal cells can adopt a variety of shapes. A phagocytic cell can even engulf other structures. There are many different types of cell. For instance, there are approximately 210 distinct cell types in the adult human body. Plant cell Plant cells are quite different from the cells of the other eukaryotic organisms. Their distinctive features are: A large central vacuole (enclosed by a membrane, the tonoplast), which maintains the cell's turgor and controls movement ofmolecules between the cytosol and sap A primary cell wall containing cellulose, hemicellulose and pectin, deposited by the protoplast on the outside of the cell membrane; this contrasts with the cell walls of fungi, which contain chitin, and the cell envelopes of prokaryotes, in which peptidoglycans are the main structural molecules The plasmodesmata, linking pores in the cell wall that allow each plant cell to communicate with other adjacent cells; this is different from the functionally analogous system of gap junctions between animal cells. 15 Plastids, especially chloroplasts that contain chlorophyll, the pigment that gives plants their green color and allows them to perform photosynthesis Bryophytes and seedless vascular plants lack flagellae and centrioles except in the sperm cells.[16] Sperm of cycads and Ginkgoare large, complex cells that swim with hundreds to thousands of flagellae. Conifers (Pinophyta) and flowering plants (Angiospermae) lack the flagellae and centrioles that are present in animal cells.

Answer the user query using only the information in the provided text.

How did verbal ability impact the results?

Background: Individuals on the autism spectrum experience various challenges related to social behaviors and may often display increased irritability and hyperactivity. Some studies have suggested that reduced levels of a hormone called oxytocin, which is known for its role in promoting social bonding, may be responsible for difculties in social interactions in autism. Oxytocin therapy has been used of-label in some individuals on the autism spectrum as a potential intervention to improve social behavior, but previous studies have not been able to confrm its efcacy. Earlier clinical trials examining oxytocin in autism have shown widely varying results. This large randomized controlled trial sought to resolve the previous contradictory fndings and determine whether extended use of oxytocin can help to improve social behaviors in children and teenagers on the autism spectrum. Methods & Findings: Tis study evaluated whether a nasal oxytocin spray could afect social interactions and other behaviors (e.g., irritability, social withdrawal, and hyperactivity) in children and adolescents on the autism spectrum during a 24-week clinical trial. Individuals between the ages of 3 and 17 were assessed by trained researchers and were selected for participation if they met the criteria for autism. Participants were then randomly assigned to receive either a nasal oxytocin spray or a placebo (i.e., a comparison nasal spray that did not contain oxytocin) every day at a series of gradually increasing doses. Participants received social interaction scores every 4 weeks based on multiple assessments that were completed by caregivers or the participant. Separate analyses were performed in groups of individuals with minimal verbal fuency and high verbal fuency. Tis study found no diference in social interaction scores between the oxytocin group and the placebo group and no diference between the groups with difering levels of verbal ability. Implications: Te fndings of this study demonstrate that extended use of a nasal oxytocin spray over a 24-week period does not make a detectable diference in measured social interactions or behaviors in children and adolescents with autism. While this study showed no observable social beneft with the use of intranasal oxytocin, there are remaining questions around issues such as the ideal dose, whether current formulations are able to penetrate the blood-brain barrier, and whether a longer intervention time course could reveal efects. In addition, future studies that use techniques such as brain imaging may reveal new information on how oxytocin might be used in autism.

Answer the user query using only the information in the provided text. Background: Individuals on the autism spectrum experience various challenges related to social behaviors and may often display increased irritability and hyperactivity. Some studies have suggested that reduced levels of a hormone called oxytocin, which is known for its role in promoting social bonding, may be responsible for difculties in social interactions in autism. Oxytocin therapy has been used of-label in some individuals on the autism spectrum as a potential intervention to improve social behavior, but previous studies have not been able to confrm its efcacy. Earlier clinical trials examining oxytocin in autism have shown widely varying results. This large randomized controlled trial sought to resolve the previous contradictory fndings and determine whether extended use of oxytocin can help to improve social behaviors in children and teenagers on the autism spectrum. Methods & Findings: Tis study evaluated whether a nasal oxytocin spray could afect social interactions and other behaviors (e.g., irritability, social withdrawal, and hyperactivity) in children and adolescents on the autism spectrum during a 24-week clinical trial. Individuals between the ages of 3 and 17 were assessed by trained researchers and were selected for participation if they met the criteria for autism. Participants were then randomly assigned to receive either a nasal oxytocin spray or a placebo (i.e., a comparison nasal spray that did not contain oxytocin) every day at a series of gradually increasing doses. Participants received social interaction scores every 4 weeks based on multiple assessments that were completed by caregivers or the participant. Separate analyses were performed in groups of individuals with minimal verbal fuency and high verbal fuency. Tis study found no diference in social interaction scores between the oxytocin group and the placebo group and no diference between the groups with difering levels of verbal ability. Implications: Te fndings of this study demonstrate that extended use of a nasal oxytocin spray over a 24-week period does not make a detectable diference in measured social interactions or behaviors in children and adolescents with autism. While this study showed no observable social beneft with the use of intranasal oxytocin, there are remaining questions around issues such as the ideal dose, whether current formulations are able to penetrate the blood-brain barrier, and whether a longer intervention time course could reveal efects. In addition, future studies that use techniques such as brain imaging may reveal new information on how oxytocin might be used in autism. What is oxytocin therapy?

Read the attached text, and then answer the question that follows using only details from the context provided. You will NOT refer to outside sources for your response.

Based on the text above, what factors can contribute to wealth accumulation through homeownership?

Introduction In many respects, the notion that owning a home is an effective means of accumulating wealth among low-income and minority households has been the keystone underlying efforts to support homeownership in recent decades. The renewed emphasis on boosting homeownership rates as a policy goal that arose in the early 1990s can be traced in no small part to the seminal work by Oliver and Shapiro (1990) and Sherraden (1991) highlighting the importance of assets as a fundamental determinant of the long-run well-being of families and individuals. The efforts of these scholars led to a heightened awareness of the importance of assets in determining life's opportunities, enabling investments in education and businesses, providing economic security in times of lost jobs or poor health, and passing on advantages to children. Assessments of differences in asset ownership placed particularly emphasis on the tremendous gaps in homeownership rates by race/ethnicity and income and the importance of these gaps in explaining differences in wealth. In announcing their own initiatives to close these homeownership gaps, both President Clinton and President Bush gave prominent attention to the foundational role that homeownership plays in providing financial security (Herbert and Belsky, 2006). But while faith in homeownership's financial benefits are widely subscribed to, there have long been challenges to the view that owning a home is necessarily an effective means of producing wealth for lower-income and minority households. In 2001 the Joint Center for Housing Studies hosted a symposium with the goal of "examining the unexamined goal" of boosting low-income homeownership (Retsinas and Belsky, 2002a). The general conclusion that emerged from this collection of papers was that lower-income households do benefit from owning homes, although this conclusion was subject to a variety of "caveats and codicils" (Retsinas and Belsky, 2002b, page 11). A few of these caveats related to whether financial benefits were likely to materialize, with papers finding that all too commonly homebuyers sold their homes for real losses while alternative investments offered higher returns (Belsky and Duda, 2002; Goetzmann and Speigel, 2002). In perhaps the most comprehensive critique of the policy emphasis of fostering low-income homeownership, Shlay (2006) reviewed existing scholarly evidence to cast doubt on the likelihood that either the financial or social benefits of owning would be realized. These criticisms have only grown louder in the aftermath of the housing bust, as trillions of dollars in wealth evaporated leaving more than 10 million homeowners owing more than their homes are worth and leading to more than 4 million owners losing their homes to foreclosure (Joint Center for Housing Studies, 2012; Kiviat, 2010; Li and Yang, 2010; Davis, 2012). Many of the criticisms raised about 1 the financial risks of homeownership are not new, but the experience of the last five years has certainly given new impetus to these arguments. But there are also concerns that changes in the mortgage market and in consumer behavior may have exacerbated these risks, increasing the odds that owners will, at best, be less likely to realize any financial gains from owning and, at worse, face a heightened risk of foreclosure. The goal of this paper is to reassess in the light of recent experience whether homeownership is likely to be an effective means of wealth creation for low-income and minority households. Has the experience of the last decade proven the arguments of earlier critics of homeownership? Have changes in the market affected whether these benefits are likely to be realized? The paper takes three approaches to address these questions. We begin by presenting a conceptualization of the risks and rewards of homeownership as a financial choice, with a particular eye toward whether the odds of a beneficial outcome are lower for lower-income and minority owners. This review also assesses whether recent experience has altered this calculus-as opposed to just raising our awareness of the proper weighting of the likelihood of realizing the benefits while sidestepping the risks. Next, we review the existing literature examining the financial benefits of owning a home, including both studies simulating the returns to owning and renting as well as studies using panel surveys to track actual wealth accumulation among owners and renters. Finally, we examine data from the Survey of Consumer Finance (SCF) and the Panel Study of Income Dynamics (PSID) covering the last decade to assess how owning a home has been associated with changes in household financial balance sheets over this period. To preview our conclusions, we find that while there is no doubt that homeownership entails real financial risks, there continues to be strong support for the association between owning a home and accumulating wealth. This relationship held even during the tumultuous period from 1999 to 2009, under less than ideal conditions. Importantly, while homeownership is associated with somewhat lower gains in wealth among minorities and lower-income households, these gains are on average still positive and substantial. In contrast, renters generally do not see any gains in wealth. Those who buy homes but do not sustain this ownership also do not experience any gains in wealth, but are generally left no worse off in wealth terms than they were prior to buying a home-although of course there may still be substantial costs from these failed attempts at owning in terms of physical and mental health as well as future costs of credit. We conclude that homeownership continues to represent an important opportunity for individuals and families of limited means to accumulate wealth. As such, policies to support homeownership can be justified as a means of alleviating wealth disparities by extending this 2 opportunity to those who are in a position to succeed as owners under the right conditions. The key, of course, is to identify the conditions where lower-income and minority households are most likely to succeed as owners and so realize this potential while avoiding the significant costs of failure. Assessing the Financial Risks and Rewards of Homeownership Before turning to evidence about the financial returns to homeownership, it is helpful to start by framing the arguments about why homeownership is thought to be an effective means of generating wealth as well as the counter arguments about why these benefits may not materialize, particularly for lower-income and minority homeowners. We then consider how changes in mortgage markets and consumer behavior may have altered the likelihood that owning will lead to financial gains. This framing helps provide a basis for interpreting the findings from the following two sections of the paper that examine evidence about the association between homeowning and wealth accumulation. The Potential Financial Benefits of Owning The belief that homeownership can be an important means of creating wealth has its roots in five factors. First, the widespread use of amortizing mortgages to finance the acquisition of the home results in forced savings as a portion of the financing cost each month goes toward principal reduction. While modest in the early years of repayment, the share of the payment going toward principal increases over time. For example, assuming a 30-year loan with a 5 percent interest rate, a homeowner will have paid off about 8 percent of the mortgage after 5 years, 19 percent after 10 years, and nearly a third after 15 years. Assuming a household purchases a home in their early 30s and keeps on a path to pay off the mortgage over a thirty-year period, these forced savings will represent a sizable nest egg when they reach retirement age. In addition, an often overlooked aspect of forced savings associated with homeownership is the accumulation of the downpayment itself, which often entails a committed effort to accumulate savings in a short period. Second, homes are generally assumed to experience some degree of real appreciation over time, reflecting increased overall demand for housing due to growth in both population and incomes against a backdrop of a fixed supply of land located near centers of economic activity. Shiller (2005) has been the most notable critic of this point of view, arguing that over the very long-run real house prices have only barely exceeded inflation. Lawler (2012), however, has argued that Shiller's house price estimates and measures of inflation result in an underestimate of real house price growth. Analysis of trends in real house prices across a range of market areas support the conclusion that these trends 3 reflect a complex interaction of supply and demand factors in local markets that defy simple categorization (Capozza et al. 2002, Gallin, 2006). At a national level the Federal Housing Finance Agency house price index indicates that between 1975 and 2012 the compound annual growth rate in house prices has exceed inflation by 0.8 percentage points. Even at a modest rate of increase, the compounding of these returns over a longer period of time can be produce substantial increase in real home values. Assuming just a 0.8 percent annual real increase in house values over 30 years an owner will experience a real gain of about 26 percent in the overall house value. The use of financing can further leverage these returns. A homebuyer with a modest downpayment gets the benefit of increases in the overall asset value despite their small equity stake. While the cost of financing can create a situation of negative leverage if the increase in house values is lower than the cost of financing (so that the financing costs exceed the increase in the asset value), this risk diminishes over time as the value of the house compounds while the debt payment is fixed. Through leverage, the rate of return on an investment in a home can be substantial even when the increase in house values is modest. Consider the case where a buyer puts down 5 percent and the house appreciates at 4 percent annually. After 5 years the home will have increased in value by nearly 22 percent or more than 4 times the initial 5 percent downpayment. Even allowing for selling costs of 6 percent, this would represent an annualized return of 31 percent on the owner's initial investment. Due to leverage, even nominal increases in home values that do not exceed inflation can result in real returns. In the above example, if inflation matched the 4 percent growth in home prices, the owner would still have earned a substantial real return on their initial investment. Federal income tax benefits from owning a home can also be substantial. The ability to deduct mortgage interest and property taxes is the most apparent of these benefits. Taxpayers who are able to make full use of these deductions receive a discount on these portions of ongoing housing costs at the taxpayer's marginal tax rate, ranging from 15 percent for moderate income households up to 39 percent for the highest tax bracket. In addition, capital gains on the sale of a principal residence up to $250,000 for single persons and $500,000 for married couples are also excluded from capital gains taxation, which is currently 15 percent for most households and 20 percent for the highest income bracket.1 1 An additional tax benefit that is often overlooked is the fact that while owner occupants benefit from the use of their home as a residence they do not have to pay any tax on these benefits, referred to as the implicit rental income from the property (that is, the rent one would have to pay to occupy the home) (Ozanne, 2012). The loss of revenue to the U.S. Treasury from this exclusion is substantial, outweighing the costs of the mortgage interest deduction. 4 Finally, owning a home provides a hedge against inflation in rents over time. Sinai and Souleles (2005) find that homeownership rates and housing values are both higher in markets where rents are more volatile, indicating the value placed on being able to protect against rent fluctuations. Under most circumstances, mortgage payments also decline in real terms over time, reducing housing costs as a share of income. For long-term owners, this can result in fairly substantial savings in the out of pocket costs for required for housing. Assuming a fixed rate mortgage, inflation of 3 percent, 1 percent growth in both real house prices and the costs of property taxes, insurance and maintenance, real monthly housing costs would decline by about 10 percent after 5 years, 15 percent after 10 years, and 30 percent by the last year of the mortgage. Once the mortgage is paid off, the out of pocket costs of owning in real terms are less than half the payments made at the time of purchase. Housing costs for renters, in contrast, would be expected to keep pace with inflation in housing prices. The Potential Financial Risks of Owning Combined, the financial benefits outlined above can fuel significant wealth accumulation. But as the last few years have made painfully clear, the financial benefits associated with owning a home are not without risk. To begin with, house prices can be volatile. That was certainly the case in the wake of the housing bust, as nominal prices fell nationally by some 25 percent or more (depending upon the specific price index used), with the hardest hit markets experiencing declines of more than 40 percent. Almost no area of the country was spared from some degree of decline. According to the FHFA index, nominal prices fell in every state with the exception of North Dakota. But while recent experience is notable for the breadth and depth of price declines, there are other examples of fairly significant price declines over the last few decades, including declines of between 10 and 20 percent in some Oil Patch states in the 1980s and in New England, California and Hawaii in the early 1990s. There are also a number of markets where house prices trends have historically been more stable, but in these areas long-run real price increases have either not kept pace with inflation or have been modest. House price growth has been particularly weak in a number of markets in the Midwest and South where population and income growth have been low. Based on long-run state level indexes from FHFA, between 1975 and 2012 there were 10 states in these regions where the compound annual growth in house prices did not exceed general price inflation. Even before the bust, homeowners in these markets did not have the benefit of real growth in house prices over the long term. In nine other states house price growth did beat inflation, but by less than 0.25 percent on an annual basis. Thus, in about two-fifths of states real house price growth was either non-existent or trivial. At the other 5 extreme there were 17 states, mostly along the Pacific coast and in the Northeast that experienced real house price growth of more than 1 percent, including 5 states that exceeded 2 percent. There are also peculiar aspects of owning a home that further exacerbate the financial risks of these investments. Homeowners make a significant investment in a specific location and cannot diversify the risk of home price declines by spreading this investment across assets or across markets. Homes values are also high relative to incomes and so account for a large share of household wealth. Wolff (2012) reports that in 2010 the value of the principal residence accounted for two-thirds of total wealth among households in the middle three quintiles of the wealth distribution. With so much wealth tied up in one asset, homeowners are particularly vulnerable to changes in home values. The use of debt financing for a large share of the purchase further magnifies these risks, with even small drops in prices wiping out substantial shares of homeowner equity. Indeed, at the height of the housing bust the number of households underwater on their mortgages was estimated by CoreLogic to have exceeded 11 million while Zillow placed the number closer to 15 million. When assessed purely on the basis of real growth in values over time, housing also compares poorly to the returns offered by investments in diversified portfolios of stock or bonds. Geotzmann and Speigel (2002) compare the change in home prices in 12 market areas between 1980 and 1999 to a range of alternative investments and find that housing was consistently dominated as an investment asset by all of the financial alternatives considered, leading them to conclude that it is "surprising that housing continues to represent a significant portion of American household portfolios" (page 260). However, Flavin and Yamashita (2002) take a more expansive view of the returns on housing investments by including the value derived from occupying the unit, the use of financial leverage, and the ability to claim income tax deductions. This fuller treatment of housing's returns finds that the average rate of return was slightly below returns for investments in stocks, but the variance of these returns were also lower and so somewhat less risky. Still, even if the returns to housing are deemed to be competitive with alternative investments the concern remains that it accounts for an excessive share of low-wealth household's portfolios. Housing investments are also handicapped by high transaction costs associated with buying and selling these assets. Home buyers face fees for mortgage origination, title search and insurance, state and local taxes, home inspections, and legal fees, all of which can add up to several percentage points of the home value. Real estate broker commissions typically also command 6 percent of the sales price. These high transaction costs can absorb a significant share of home price appreciation from the first few years of occupancy. Given these high costs, home owners who are forced by circumstances to move 6 within a few years of buying will face the risk of loss of at least some share of their initial investment even if home values have risen modestly. The need to maintain the home also imposes financial risks on owners. While routine maintenance can keep both the physical structure and the home's major systems in good working order, major investments are periodically needed, such as painting the exterior or replacing the roof or heating system. These projects incur high costs that may be difficult for owners to afford. While owners may have the opportunity to plan for these investments over time, in some cases a system will fail with little warning and produce an unexpected cost that the owner cannot afford, creating a financial strain that in the most extreme cases can jeopardize the ability to maintain ownership. Finally, the financial costs of failing to sustain homeownership are high-in addition to the traumatic impacts that foreclosures can have on the health and psychic well-being of the owner (Carr and Anacker, 2012). Owners who default on their mortgage will not only lose whatever equity stake they had in the home, they are also likely to deplete their savings in a bid to maintain ownership and suffer significant damage to their credit history making it difficult and costly to obtain credit for several years to come. Factors Contributing to Wealth Accumulation Through Homeownership Whether and to what extent a homebuyer will realize the potential benefits of owning while avoiding succumbing to the risks depends on a complex set of factors. Herbert and Belsky (2006) present a detailed conceptual model of the factors that contribute to whether homeownership produces wealth over the life course, which is briefly summarized here. The most obvious factor is the timing of purchase relative to housing price cycles. The recent boom and bust in house prices presents a prime example. Homebuyers who bought in the early 2000s were poised to benefit from the massive run-up in prices that occurred in many markets, while those that bought in the mid 2000s entered just in time for the historic freefall in prices that followed. While other price cycles in recent decades may not have been as dramatic, the consequences of buying near troughs or peaks on wealth accumulation would have been similar. Belsky and Duda (2002) examined data on repeat sales in four market areas between 1982 and 1999 and found that roughly half of owners who bought and sold their homes within this time period failed to realize gains that beat inflation after assuming a 6 percent sales cost (although most did earn a return in nominal terms). Whether owners realized a positive return depended strongly on where in the housing price cycle they bought and sold their homes. 7 Belsky and Duda (2002) conclude that "although the golden rule of real estate is often cited as location, location, location, an equally golden rule is timing, timing, timing" (Page 223). Their conclusion points to another critical factor in how likely a home is to appreciate in value - in what market and in which specific neighborhood the home is located. As noted above, there have been sizeable differences across market areas in long-term house price trends, with areas along the coasts experiencing real gains of one percent or more over the last several decades while areas in the Midwest and South have had little or no gains. But there are also substantial variations in price trends across neighborhoods within a single market (for reviews of this literature see Herbert and Belsky, 2006; Dietz and Haurin, 2003; and McCarthy, Van Zandt and Rohe, 2001). Whether a household bought a home in Boston or Cleveland is an important factor in the returns realized, but so is whether the home was in a desirable area or a declining neighborhood. The terms of financing used to buy the home also matter. Higher interest rates lower the share of payments that are devoted to principal reduction in the early years of repayment, slowing wealth accumulation. The higher monthly costs of the mortgage also erode the ability of the household to meet other expenses and to save on an ongoing basis as additional interest payments over the life of the mortgage can be substantial. For example, over a thirty-year term a loan for $150,000 at 7 percent interest will require $69,000 more in interest payments than a 5 percent loan. Higher origination fees also sap savings, reducing the quality and size of home that is affordable and lowering the rate of return on housing investments. Choices about refinancing over time can also exert a strong influence on wealth accumulation. Taking advantage of declines in mortgage interest rates to reduce financing costs can save owners hundreds of dollars each month, and tens of thousands over the life of a mortgage-although continually resetting the term of the mortgage will reduce opportunities for forced savings. On the other hand, refinancing to take cash out of the property can erode wealth accumulation, particularly if the extracted funds are used to finance consumption rather than investments in the home, education, business or financial opportunities. Wealth accumulation will be further undermined if the new loan comes with high fees and higher interest rates. Of course, the ability to tap housing wealth as a buffer against income shocks is one of the virtues of developing this cushion, but using home equity to finance an unaffordable lifestyle is an unsustainable path. A host of other factors come into play in determining how much housing wealth is realized over the span of a lifetime. For example, buying higher valued homes-if successful-can produce more wealth both through forced savings and by earning returns on a higher valued asset. By the same 8 means, those who trade up to more expensive homes over time may also accrue greater housing wealth. The age at which a first home is purchased can also be significant, giving the household a longer period to accumulate wealth. Of course, the quality of the home purchased and the owner's ability to maintain it will also affect both ongoing maintenance costs and how much the home appreciates over time. But arguably the most fundamental factor-the true golden rule of how to accumulate wealth. through homeownership-is whether ownership is sustained over the long term. Housing booms aside, many of the financial benefits are slow to accumulate, including the slow build up of forced savings, the compounding of values at low appreciation rates, and the decline in monthly housing costs in real terms over time. The expression "time heals all wounds" may also be applicable to many of homeownerships most critical risks. The losses associated with buying near the peak of a price cycle will diminish over time as owners benefit from the next upswing in prices. And even in areas whether real growth in house prices does not occur or is limited, over the long term owners will still amass some degree of wealth through paying off the mortgage and as a result of savings from lower housing costs. On the flip side, a failure to sustain homeownership-particularly when the end result is a foreclosure-will wipe out any accrued wealth and bring additional costs in the form a damaged credit history that will incur further costs over time and limit opportunities to buy another home in the near term. To some degree whether ownership is sustained will depend on choices that owners make over time - including whether the home they buy is affordable, whether they make prudent choices about refinancing, and whether they maintain the home to avoid larger home repair bills. But whether owning is sustained also will depend on whether the household can weather any number of significant events that can fundamentally alter their financial circumstances, such as loss of a job, a serious health problem, or change in the family composition due to the birth of a child, death, divorce, or the need to care for a parent or relative. Over the course of a lifetime, these events are likely to befall most everyone. Whether homeownership can be sustained in the wake of these events will depend on the ability of the household to adjust to their changed circumstances and whether they have enough available savings to cushion the blow. Impediments to Wealth Creation among Lower-Income and Minority Homeowners Up to this point the discussion presented has considered homeownership's financial risks and rewards in a general sense. But the concern of this paper is specifically with the potential for homeownership to serve as an effective means of wealth accumulation for lower-income and minority 9 households. How are the odds of generating wealth as a homeowner likely to differ for these households?? In keeping with the fundamental importance of sustained homeownership to accumulate wealth, the chief concern is that these groups of homebuyers face a more difficult time in maintaining ownership. Studies analyzing panel data to document homeownership spells among first-time buyers consistently find that low-income and minority owners have a lower probability of maintaining homeownership for at least five years. In an analysis of the National Longitudinal Survey of Youth (NLSY) from 1979 through 2000 Haurin and Rosenthal (2004) find that ownership is less likely to be sustained among both these groups. Specifically, only 57 percent of low-income buyers were found to still own their first home five years later, compared to 70 percent of high-income owners (with income categories defined by income quartiles at age 25). First homeownership spells were also found to be much shorter for minorities, averaging 6.5 years among whites, compared to 4.4 years for blacks and 5.4 years for Hispanics. In an analysis of the PSID covering the period from 1976 through 1993 Reid (2004) had similar results, with only 47 percent of low-income owners still owning their first homes 5 years later compared to 77 percent of high income owners (with incomes here defined based on average income in the years prior to homeownership compared to area median incomes). Reid further found that minorities had a harder time staying in their first home, with 42 percent of low-income non-whites still owning after five years compared to 54 percent of low-income whites. While these results raise clear concerns about the high risk of failed homeownership among these groups, the focus on a single homeownership spell may overstate the extent to which homeowning is not sustained in the long run. Haurin and Rosenthal (2004) also examine subsequent tenure experience in their panel and find that the share of households that return to owning a second time is very high for both whites and minorities. Over the 21 year period in their panel, 86 percent of whites who ever bought a home either never returned to renting or regained owning after a subsequent spell as a renter, with only slightly lower rates for blacks (81 percent) and Hispanics (84 percent). However, they do find that minorities spend more years in their intervening spells as renters, which reduces the overall amount of time they can accumulate benefits from owning. Another critical difference in the financial returns to owning for low-income households is that the ability to deduct mortgage interest and property taxes from federal taxable income may be of little or no value. In order to benefit from these tax provisions, the amount of available deductions must 2 Galster and Santiago (2008) provide a useful framing of this issues and a comprehensive review of the relevant literature. 10 exceed the standard deduction, which stood at $5,950 for individuals and $11,900 for married couples in 2012. For taxpayers with lower valued homes, particularly married couples, the costs of mortgage interest and property taxes even when added to other deductions for state taxes and charitable contributions, may not greatly exceed the standard deduction. In addition, the value of these deductions depends on the taxpayer's marginal tax rate, which will lower for low- and moderate-income households. In fact the share of the total value of the mortgage interest deduction going to moderate income households is fairly small. According to estimates from the Joint Committee on Taxation (2013), only 3 percent of the total deductions went to filers with incomes under $50,000, 9 percent to those with incomes between $50,000 and $75,000, and 11 percent to those with income between $75,000 and $100,000, leaving 77 percent of the benefit going to those earning above $100,000. To the extent that these tax benefits swing the financial scales in favor homeownership, this tilting of the calculus is not very evident for low- and moderate-income tax filers. There are also systematic differences in mortgage terms and characteristics by income and race/ethnicity that can also affect the financial returns to owning. The development of the nonprime lending industry that began in the 1990s and came to full blossom during the housing boom produced much greater variation in mortgage terms and pricing than had previously been evident. A fairly extensive literature has documented the greater prevalence of subprime lending among minorities and, to a lesser extent, low-income borrowers and communities (see, for example, Bradford, 2002; Calem, Gillen and Wachter, 2004; Apgar and Calder, 2005; Avery, Brevort, and Canner, 2007; Belsky and Richardson, 2010). As described above, higher costs of financing can significantly reduce the financial benefits of owning. While the expansion of financing options beyond a "one size fits all who qualify" approach to lending has the potential to extend homeownership opportunities to a greater range of households, there is significant evidence that the cost of credit was often higher than risk alone would warrant. Bocian, Ernst and Li (2008) present perhaps the most compelling evidence through an analysis of a large data set on nonprime loans that documents a wide range of risk measures, including credit scores as well as income and race/ethnicity. They find that even after controlling for observable differences in credit quality both blacks and Hispanics were significantly more likely to obtain high- priced mortgages for home purchase, while blacks were also more likely to obtain higher-priced refinance loans. These higher costs of borrowing not only limit the wealth producing capacity of homeownership, they also increase the risk of failing to sustain homeownership. In fact, Haurin and Rosenthal (2004) find that a 1 percentage point increase in the mortgage interest rate increases the rate of homeownership termination by 30 percent. 11 Low-income and minority borrowers are also less likely to refinance when interest rates decline. In an analysis of loans guaranteed by Freddie Mac during the 1990s Van Order and Zorn (2002) find that low-income and minority borrowers were less likely to refinance as interest rates fell. Their analysis also found that once borrower risk measures and loan characteristics were taken into account there were no remaining differences in refinance rates by income-although this just indicates that refinancing may be constrained by credit factors. Minorities, on the other hand, still had lower rates of refinancing even after controlling for these factors, suggesting that there were impediments to refinancing by these borrowers that were in addition to measurable credit factors. Nothaft and Chang (2005) analyze data from the American Housing Survey (AHS) from the late 1980s through 2001 and also find that minority and low-income owners were less likely to refinance when interest rates declined. These authors use their results to estimate the foregone savings from missed refinance opportunities, which are more than $20 billion each for black and low-income homeowners. To the extent that low-income and minority homebuyers may be more likely to purchase homes in poor condition they are also exposed to greater risks of high costs of maintenance and repair. Herbert and Belsky (2006) find that compared to whites, black and Hispanic first-time homebuyers were more likely to buy homes that were moderately or severely inadequate as characterized by the AHS- 6.5 percent for blacks and 8.8 percent for Hispanics compared to 4.3 percent among whites. A similar gap was also evident between low- and high-income households. While there has been little study of the incidence of unexpected home repair needs, a study by Rohe and his colleagues (2003) of participants in homeownership counseling programs found a fairly significant incidence of the need for unexpected repairs. Roughly half of 343 recent homebuyers reported that they had experienced a major unexpected cost in the first few years after buying their home, with the most common problem being a repair to one of the home's major systems. Finally, there are also concerns that lower-income households and minorities may be more likely to purchase homes in neighborhoods with less potential for house price appreciation. This is a particularly salient issue for minorities given the high degree of residential segregation by race and ethnicity that continues to be evident in the US. However, Herbert and Belsky (2006) present a detailed review of this literature and conclude that "taken as a whole the literature indicates that there is no reason to believe that low-value segments of the housing market will necessarily experience less appreciation than higher-valued homes. In fact, at different points in time and in different market areas, low-valued homes and neighborhoods have experienced greater appreciation rates. Although the opposite is also true." (Page 76) The evidence about differences in appreciation rates by neighborhood 12 racial composition is less definitive. Here Herbert and Belsky (2006) conclude that "it does appear that homes in mostly black areas may be less likely to experience appreciation, but this conclusion is tempered by the small number of studies and the fact that they mostly analyzed trends from the 1970s. and 1980s, which may no longer be relevant" (page 77). Findings by Boehm and Schlottmann (2004) regarding differences in wealth gains from homeownership by race and income are instructive in this regard. They find that over the period from 1984 to 1992 there was little difference in appreciation rates in the specific neighborhoods where minorities and low-income households lived. Instead, they found that differences in housing equity accumulation were tied to the lower valued homes and the shorter duration of ownership for lower- income and minority households. Thus, differences in appreciation rates may be less of a concern in whether housing leads to wealth accumulation than these other considerations. Re-assessing the Calculus of Wealth Accumulation through Homeownership As the above review has shown, there were significant concerns about the risks of homeownership as an investment well before the housing bubble burst. For critics of homeownership as a wealth building tool the experience of the housing bust was in many respects a confirmation of their fears. Still, there were several markets developments during the boom years that magnified these preexisting risks. Most notably there was a marked increase in the prevalence of riskier mortgages, including those calling for little or no documentation of income, adjustable rate loans that exposed borrowers to payment shocks from the expiration of initial teaser rates or reduced payment options, allowances for higher debt to income ratios, and greater availability of loans for borrowers with very low credit scores. Downpayment requirements also eased as loan-to-value ratios (LTVs) of 95 percent or more became more common and borrowers also used "piggyback" second mortgages to finance much of the difference between the homes' value and a conforming first mortgage at an 80-percent LTV. Not unrelated to the greater availability of mortgage credit, house prices also exhibited much greater volatility than in the past, with a dramatic increase in prices that greatly outpaced trends in both incomes and rents and belied an unsustainable bubble. The greater availability of credit also increased the opportunity for lower-income households to miss-time the market. Belsky and Duda (2002) found that during the 1980s and 1990s lower-valued homes were less likely to be transacted around market peaks, so buyers of these homes were less likely to buy high and sell low. They speculated that this was due to the natural affordability constraints that took hold as markets peaked. But during the boom of 13 the 2000s lower-valued homes experienced greater volatility in prices, arguably reflecting much greater credit availability at the peak than was true in past cycles (Joint Center for Housing Studies, 2011). However, there are good reasons to believe-or certainly to hope-that the conditions that gave rise to this excessive risk taking and associated housing bubble will not be repeated any time soon. The Dodd-Frank Act includes a number of provisions to reduce the degree of risk for both borrowers and investors in the mortgage market. The Qualified Mortgage (QM) is aimed at ensuring that borrowers have the ability to repay mortgages by requiring full documentation of income and assets, setting tighter debt to income standards, and excluding a variety of mortgage terms that expose borrowers to payment shocks. The Qualified Residential Mortgage (QRM) is aimed at ensuring greater protections for investors in mortgage backed securities by requiring the creators of these securities to retain an interest in these investments if the loans included in the loan pool do not conform to certain risk standards that essentially mirror those of the Qualified Mortgage. Dodd-Frank also established the Consumer Financial Protection Bureau to fill a gap in the regulatory structure by creating an agency charged with looking out for consumers' interests in financial transactions. Beyond these regulatory changes, there is also a heightened awareness of the risks of mortgage investments on the part of private sector actors who have suffered significant financial losses with the bursting of the housing bubble. Regulatory changes aside, these private actors are unlikely to embrace riskier lending any time soon. The Federal Reserve and other federal regulators are certainly more attuned to the possibility of a bubble in housing prices and so are more likely to act in the event that signs of a bubble re-emerge. But even in the absence of the excessive risks of the last decade, homeownership will remain a risky proposition. Thus, at best, we may return to the market conditions that existed prior to the boom and the real risks that these conditions posed for investments in owner-occupied housing. In that regard, an assessment of experience in wealth creation through homeownership prior to the boom is relevant for what we might expect in the future. On the other hand it does seem likely-and arguably even desirable given how tight credit has become-that some greater degree of risk taking will emerge to make credit available to the many lower-income and lower-wealth households that would like to own a home. In fact, the QM standard of a total debt-to-income ratio of up to 43 percent does curtail the higher levels that became evident during the boom, but this cutoff still represents a liberalization from standards for conventional mortgages that prevailed in the 1990s. There may also have been a shift in consumer attitudes toward mortgage debt, with fewer households seeking to pay off mortgages over time and thus exposing themselves for longer periods to the risks associated with these leveraged investments. Over time, as 14 conditions return to normal and the market adjusts to new regulatory structures, we are likely to see mortgages originated outside of the QM and QRM boxes. In that regard, an assessment of the experience of homeowners through the boom and bust is instructive as a stress test of how likely homeownership is to build wealth under more extreme market conditions. The next two sections of the paper look to assess homeownership's potential for wealth building from these two perspectives. First by presenting a review of the literature assessing homeownerships' association with wealth building prior to the 2000s and then by analyzing data from the last decade to examine how homeownership was associated with changes in wealth through the turbulent conditions of the 2000s. Review of Previous Studies Assessing the Financial Returns to Homeownership As the discussion up to this point has intended to illustrate, whether owning a home will lead to the accumulation of wealth is the result of complex set of factors related to the choices that households make in buying their home and how these choices interact with market conditions both at the time of purchase and over time. This complexity makes it quite difficult to assess whether in practice owning is likely to be an effective means of increasing a household's wealth. A further complicating factor is that there is a substantial selection bias in who becomes a homeowner, as there is reason to believe that those who are most secure in their financial condition and most inclined to save are more likely to become owners. For this reason, comparisons of the wealth profiles of owners and renters may not be able to attribute any observed differences solely to the influence of homeownership on the ability to accrue wealth. There are two broad classes of studies that have attempted to assess the financial benefits of homeownership in light of these challenges. One group relies on simulations that compare the theoretical costs and benefits of owning and renting under a variety of assumptions about market conditions and household choices. A key appeal of these studies is that they essentially remove concerns about selection bias by assuming otherwise identical households operate under a consistent set of decision rules. They can also isolate the influence of specific factors to shed light on the paths that are most likely to make owning or renting financially beneficial. But while these studies highlight the potential financial returns to owning and renting, they do not capture how households are likely to actually behave in these situations and so leave open the question of whether the potential returns of these tenure choices are likely to be realized in practice. 15 Another group of studies rely on panel studies that track households over time to examine how choices about owning and renting are correlated with changes in wealth. The findings from this type of analysis provide evidence of whether in practice owners are more likely to accrue wealth than renters and how this experience differs by income and race/ethnicity. Where the theoretical comparisons of owning and renting also generally focus on a single spell of homeownership - that is, the financial outcome associated with the period between buying and selling a single home - panel studies can track households through multiple transitions in and out of owning to assess outcomes from a series of tenure choices over time. The main drawback of these studies is the lingering concern that owners may be inherently different from renters in ways that observable household characteristics cannot capture. Some of these studies employ statistical methods to try to control for this selection bias, although it is doubtful that these controls can fully account for these differences. Both classes of studies provide important insights into the opportunities and drawbacks of homeownership as a means of increasing household wealth. When viewed as a whole the findings from both streams of research help paint a clearer picture of whether and how homeownership may help foster wealth creation. The sections that follow highlight key findings from each of these literature strands. Simulations of the Financial Returns to Owning and Renting Beginning with Mills (1990) there have been a number of studies that have simulated the financial returns to owning and renting under a variety of assumptions to identify whether and under what circumstances owning or renting is likely to be more financially beneficial (Capone, 1995; Belsky, Retsinas, and Duda, 2007; Rappaport, 2010; Beracha and Johnson, 2012). While the studies differ in important respects, the general approach is to compare the "all-in" costs of owning - including mortgage interest, property taxes, insurance, maintenance, and transaction costs along with offsetting gains in property value - to the costs of renting a comparable housing unit. Either implicit or explicit in these comparisons is that renters save and invest both the initial investment that owners make in buying their homes as well as any annual savings in housing costs. There are a host of assumptions that underlie these calculations, but among the most influential factors are the estimate of rents as a share of house value, the length of time the home is owned, the basis for simulating trends in house prices and rents over time, and the treatment of income tax benefits. The studies differ in fundamental ways related to the range of assumptions tested and the method for comparing returns to owning and renting and, as a result, individually reach somewhat 16 different conclusions about which tenure choice is likely to be preferred. But collectively the studies lead to some general conclusions about the relative financial merits of owning and renting. Perhaps the most fundamental conclusion from these studies that runs counter to the prevailing sense that homeownership is a powerful source of wealth is that under a variety of conditions renting is often more likely to be a better financial choice than owning. Belsky, Retsinas and Duda (2007) compare owning and renting in four different market areas chosen to represent different degrees of price appreciation and volatility over the period studied from 1983 through 2001. They focus on holding periods of 3, 5 and 7 years during their window of study and report the share of different holding periods where owning results in higher financial returns than renting. Overall they find that in only 53 percent of the 3-year holding periods would owning be preferred to renting. Increasing the holding period to 7 years-which allows for more time to work off the high transaction costs of buying and selling a home-only increases this proportion to 63 percent. Rappaport (2010) reaches a similar conclusion based on an analysis of national trends in market conditions between 1970 and 1999 and an assumed 10-year period of owning a home. He finds that owning a home unambiguously built more wealth in about half of the possible 10-year periods, renting was clearly better in another quarter and likely, but not unambiguously, preferred in the remaining periods. Finally, Beracha and Johnson (2012) come to a similar conclusion in an analysis of all possible 8-year holding periods given actual market conditions at both the national and regional level between 1978 and 2009. They find that between 65 and 75 percent of cases renting offered greater opportunities for accruing wealth than owning, depending on whether renters employing a more conservative or aggressive investment approach. In parsing the findings of these studies, there are several factors that are the critical drivers of the results. Perhaps the most obvious is the importance of the timing of home purchase relative to market cycles in prices and interest rates. Depending on the future course of prices, rents and interest rates one or the other tenure would be strongly preferred at different points in time. The importance of timing may be most clearly demonstrated in Belsky, Retsinas and Duda (2007) when they consider different holding periods among owners. In general, it would be expected that longer holding periods should favor owning as more time is allowed to overcome high transaction costs, pay down additional principal, and ride out price cycles. Instead, they find that in most markets the likelihood of owning being preferred to renting was little changed by the holding period as short holding periods offered the possibility of catching only the upswing in prices while longer holds made it more likely that owners would share in some portion of a downturn. Only in Chicago, which did not experience such dramatic swings in prices, were longer holding periods found to be much more likely to benefit owning. 17 Still, the issue of holding period is an important consideration. The analysis by both Mills and Capone solved for the holding period that was needed for owning to yield a higher return than renting on the assumption that longer holding periods would always favor homeownership. In his base case scenario Mills found a holding period of slightly longer than 7 years was needed for owning to be preferred. The more recent studies that have showed the importance of market timing either assumed a single fixed holding period of 8 to 10 years (as in Beracha and Johnson and Rappaport) or a range of relative short holding periods (as in Belsky, Retsinas and Duda). If owning does become more favorable over a longer period of time - for example, slightly longer than 8 to 10 years - these assessments would not capture this. In fact, many households move in and out of homeownership over time so a more complete assessment of the financial implications of tenure choice would take into account multiple homeownership spells. While one spell of owning may yield low returns, if homeowning is sustained or resumed then the household may yet benefit from the next upswing. Another important factor driving the findings are assumptions made about rents as a share of house value. This ratio is difficult to estimate both because of systematic differences in the nature of the owner and renter occupied stock and because market values and rents are hard to observe simultaneously. How much renters have to pay to rent a comparable home is obviously a key driver of financial outcomes as it determines how much they can save annually by renting, thereby adding to their wealth. Mills (1990) found that among the variables used in his simulation, his results were most sensitive to the ratio of rents to house values as a single percentage point change up or down leading to fluctuations in the required holding period from 3 to 23 years. Capone (1995) built on Mills study to examine the rent-versus-buy decision specifically for lower income households. He makes note of the importance of the rent-to-price ratio assumption and argues that Mills assumption of 7 percent was well below the ratios observed in low-cost segments of the market, where ratios of 10 to 12 percent were more reasonable. Under Capone's assumption that renters faced much higher rents he found that owners only needed to hold onto their homes for about 3 years for owning to be preferred. In contrast, Belsky, Retsinas and Duda rely on rent to price ratios is in the range of 5 to 7 percent, while the series used by Beracha and Johnson derived by Davis, Lehnert, and Martin (2008) appears to average about 5 percent. In both cases these assumptions are more favorable to renting than the assumptions used by either Mills or Capone. In recognition of the importance of this assumption, Rappaport structures his analysis to estimate the rent-to-price ratio that is the breakeven point between owning and renting. He then compares this estimate to what he feels is a plausible range for this ratio of 18 between 5 and 10 percent based on analysis of different market areas over time. At the higher end of this range owning would almost always be preferred, while the lower end leads to his conclusion that owning is clearly preferred to renting in only about half of the holding periods considered. In short, high or low values of this ratio can swamp other considerations, yet, as Rappaport demonstrates, pinning down actual values for this ratio is not an easy task. Several of the studies have examined the issue of whether tax benefits are important to whether owning makes more financial sense than renting. Mills assumes that owners can take full advantage of tax benefits at a 28 percent marginal rate. When he reduces the marginal rate to 15 percent he finds that owning is never preferred. Capone, though, demonstrates, that this knife edge does not hold if a higher rent to price ratio is assumed. In his base case analysis, owners are only assumed to benefit from tax benefits if they exceed the standard deduction and since he assumes a much more modest house in keeping with his focus on lower-income households, the tax benefits are essentially non-existent. As a result, reducing the tax benefits in his analysis does not change his conclusion that owning is a better financial choice even after only a few years. Belsky, Retsinas and Duda also examine the importance of tax benefits for lower-income owners. Like Capone, they adjust the value of tax deductions to account for the size of the home purchased and the amount of the standard deduction. They also find that tax benefits by themselves generally do not change the calculus of whether owning beats renting financially. So while tax benefits are an important factor among higher income households, as Mills found, it has little effect on the calculus for lower-income households. Despite getting limited benefits from tax breaks under a variety of circumstances Capone and Belsky, Retsinas and Duda find that lower-income households can fare better financially by owning. Belsky, Retsinas and Duda also make a unique contribution by examining how the returns to homeownership are affected by higher mortgage costs. They examine two scenarios: one where owners face interest rates that are 2 percentage points higher than prime rates and another where they are 5 percentage points higher. Under the first scenario, the likelihood that owning would be preferred to renting is decreased by moderate amounts (between 6 and 17 percentage points), while under the later scenario owning is rarely a better financial choice than renting. In short, they find that higher interest rates do reduce the financial appeal of homeownership, although the impact is most pronounced at extremely high levels. Lastly, and in some ways most critically, the finding that renting offers the potential for higher returns than owners depends in large part on renters taking steps to invest the annual savings in housing costs compared to renting. Building on Beracha and Johnson (2012), Beracha, Skiba, and 19 Johnson (2012) examine how variations in key assumptions regarding trends in prices, rents, interest rates, downpayment shares, and the returns available from alternative investments affect the buy versus rent financial calculus. They find that modifying most factors in isolation have only a moderate effect on whether renting is favored over owning. However, when they drop the assumption that renters actual invest any annual savings in housing costs on top of the initial downpayment they find that renting rarely results in higher wealth than owning. Thus, they find that the forced savings aspect of homeownership is of fundamental importance in determining whether owning will lead to greater wealth. This finding is echoed in the results of Boehm and Schlottmann (2004) who employ a somewhat unique approach to simulating the impact of homeownership on wealth accumulation. This study uses the Panel Study of Income Dynamics (PSID) to model the probability of moving in and out of homeownership on an annual basis over the period from 1984 through 1992. These same data are also used to estimate the house value that a household would opt for if a home were purchased in a given year. The estimated house value is then inflated based on house price trends in the census tract where the household resided to yield each household's expected gain in wealth from homeownership. This analysis finds that while minorities and low-income households do accrue wealth from homeownership, the amounts are much less than for higher income whites both because they own for fewer years and because they buy lower valued homes. But importantly, while the expected wealth accumulation among these households is less than that earned by higher income whites it is still positive. The authors also use the PSID to document that these same low-income and minority households essentially had no growth. in non-housing wealth over the same period. So in that regard the estimates of potential wealth created through homeownership were all the more important. Evidence from Panel Surveys about Wealth Accumulation through Homeownership As the findings from Beracha and Johnson (2012) and Boehm and Schlottmann (2004) suggest, the theoretical advantages of renting may not be realized if in practice renters do not take advantage of the opportunities afforded to them for saving and investing derived from the lower cost of renting. In contrast, studies making use of panel surveys that track households over time provide insights into the wealth accumulation associated with actual choices about renting and owning. These studies universally find that owning a home is associated with higher levels of wealth accumulation even after controlling for a range of household characteristics. While the gains are also consistently smaller in magnitude for lower-income and minority households, these studies also find that in contrast to owners similar renters 20 experience little or no gains in wealth. These findings hold even when steps are taken to account for selection bias in who becomes a homeowner. Although these methods may not fully account for the differences between owners and renters, there remains a strong case that homeowning does make a positive contribution to household balance sheets regardless of income or race/ethnicity. Haurin, Hendershott and Wachter (1996) was among the first studies to use panel survey data to track wealth trajectories associated with homeownership. The primary focus of this study was on the accumulation of wealth in anticipation of becoming an owner rather than how owning a home over time contributes to wealth accumulation, but their findings provide important insights into one way in which homeownership adds to wealth. They use the National Longitudinal Survey of Youth (NLSY) to track young renters age 20 to 28 in 1985 through 1990 and observe both their annual wealth levels and the timing of any transitions into homeownership. They find that household wealth goes up markedly during the transition to homeownership, increasing by 33 percent on average in the year prior to buying a home and then more than doubling in the year they first own. When they examine factors that contribute to this jump in wealth they find that marrying makes a significant contribution along with an increase in hours worked and a slightly higher incidence of inheritance and gifts. Their results suggest that an important mechanism by which homeownership adds to wealth is through the incentive to save in anticipation of buying a home. Even before realizing any returns on the investment in the home itself, the drive to become an owner results in substantially higher wealth than those who remain renters. Adding to this effect Haurin and his colleagues also find that wealth increases more rapidly in the years after becoming a homeowner-by 17 percent on average annually among their sample. Reid (2004) uses panel data from the PSID for the period 1976 through 1994 to examine the financial outcomes of homeownership among low-income households who bought their first home at some point during this period (with low-income defined as those with incomes consistently below 80 percent of area median income before first buying a home). She takes two approaches to examining the returns to homeownership for this group. First, she estimates the change in home values for both low- income and minority homeowners compared to higher-income and white owners. She finds that the rate of increase in home values for these groups was fairly modest, failing to beat the returns that would have been earned on an investment in Treasury bills over the same time. Reid then examines wealth holdings of households by tenure status at the end of her period of observation. She finds that while low-income and minority owners generally built much less wealth than higher-income and white households, the amount of their housing wealth was non-trivial and was many times larger than their other forms of wealth. Like Boehm and Schlottmann, she also finds that those who were renters at the 21 end of the period essentially held no wealth of any kind. Reid, however, does not undertake a multivariate analysis to control for other factors that may account for the differences between owners and renters. Nor does she factor in the impact of failed efforts at homeownership on wealth. But the fact that home equity accounts for such a large share of wealth among low-income and minority households points to the important role that owning a home played in fostering wealth accumulation. Di, Belsky and Liu (2007) was the first study to directly assess the relationship between homeownership and wealth accumulation over time while attempting to account for household characteristics and to include some measure of potential selection bias in who becomes an owner. The study uses the PSID to track households who were renters in 1989 through 2001 to observe transitions into and out of homeownership. The change in household wealth over time is then modeled as a function of starting wealth, a range of household characteristics thought to influence wealth, and, their principal measure of interest, the amount of time spent as an owner. In order to take into account a household's propensity to save, the study uses the PSID from 1984 through 1989 to estimate the share of income that was saved as an indication of savings behavior prior to the period when tenure transitions are observed as a means of controlling for this tendency in assessing differences in savings behavior after buying a home. Their principal finding is a positive and statistically significant association between additional years of homeownership and changes in wealth. The authors include a square term for the number of years owned to take into account anticipated impacts of the timing of moves into homeownership over the period as there was an initial decline in house values during the first years of their panel followed by more robust increases in later years. This square term is negative and significant indicating those who bought earlier in the period had lower cumulative gains in wealth. The largest estimated gains in wealth of $13,000 per year of ownership occurred among those who owned for 8 years. But for those who owned for the maximum possible period of 12 years the gains were only $3,333 per year. Prior savings tendency was positively associated with increases in wealth as expected, but was not statistically significant and so did not appear to capture any important difference in household behavior that was not already accounted for by other explanatory variables. Turner and Luea (2009) undertake a very similar analysis using the PSID sample for the period from 1987 to 2001. In contrast to Di, Belsky and Liu who only include initial renters, their study sample includes all households in the sample as of 2001 that were age 65 or younger regardless of whether they were renters at the start of the period. The study pools observations for the sample on household wealth from three points in time: 1994, 1999, and 2001. For each observation they include a count of the number of years the household has owned a home since 1988 as their explanatory variable of 22 interest. The approach used in this study attempts to control for selection bias into homeownership by estimating a random effects model that includes a household specific constant term. Turner and Luea also separate the sample into two income classes to see whether the association between homeownership and wealth growth differs by income. Low- and moderate-income (LMI) households were those who had incomes below 120 percent of area median income in all three periods when wealth was observed. The results indicate that each year of homeownership is associated with nearly $14,000 in additional wealth, perhaps not surprisingly quite similar to the amount found by Di, Belsky and Liu using the same survey over a nearly identical period (although with a somewhat different sample). When controls are included for LMI status, Turner and Luea find that these households have somewhat lower wealth accumulation of between $6,000 and $10,000 per year. But they note that since the average wealth holding of LMI households in 2001 was about $89,000 this annual rate of increase accounts for a fairly sizeable share of total wealth. In an unpublished dissertation, Mamgain (2011) extends the work of Turner and Luea by employing a two-stage model to add stronger controls for selection into homeownership. Like most of the other studies, Mamgain also uses the PSID, but his period of observation is from 1999 through 2007. Despite the different time period examined, when he replicates Turner and Luea his analysis yields similar results regarding the magnitude of the association between homeownership and wealth (although by ending the study period in 2007 it does not include the sharp loss of both housing and financial wealth that followed 2007). When Mamgain adds additional controls to his model to capture the intention to move, the respondent's health status, their ownership of other real estate and an estimate of current LTV he finds a somewhat lower impact of additional years of owning, but the estimate is still significant and positive. Importantly, when he employs his two-stage approach to include both a selection term and an instrumental measure of current tenure his estimate of the impact of each. additional year on owning does not change. He also estimates separate models by income level and finds that there is no difference in the impact of owning across income classes—all are positive and significant. In short, like other studies he does not find a significant impact of selection bias on his findings and he also finds that low-income owners are also likely to benefit from owning homes. 3 3 He does differ from previous studies in how he estimates the contribution of owning to wealth gains, by focusing on impacts at much lower household wealth levels. He finds that assuming wealth of about $2,500 for the lowest income group (at or below 150 percent of the poverty level) owning a home only adds a few hundred dollars a year to the household's bottom line. But with total wealth set a level well below the median among owners in this income class this result seems implausible. 23 None of the studies estimating statistical models to assess the contribution of homeownership to wealth accumulation analyzed whether there were differences in this experience by race and ethnicity. As discussed above, there are significant racial and ethnic differences in residential location, size of home, and characteristics of financing used, all of which could contribute to differences in wealth outcomes. Shapiro, Meschede, and Osoro (2013) use the PSID from 1984 through 2009 specifically to examine the factors associated with more rapid growth in wealth among whites over this period compared to blacks. Tracking the same set of households over this period they find that gains in median wealth among whites exceeded those among blacks by $152,000. Based on the results of a multivariate analysis they found that the single largest driver of this divergence in wealth was the additional time whites spend as homeowners, which they estimate accounted for 27 percent of the additional white gains. The next most significant factors were differences in income (20 percent), unemployment spells (9 percent), lower shares with a college education (5 percent), and differences in inheritance and financial support from family (5 percent). They also find that years of homeownership exerted a stronger influence on gains in wealth for blacks than it did for whites. While the authors do not attempt to control for any selection bias to control for who becomes a homeowner, none of the previous studies that have taken these steps have found these controls to change their findings. Conclusions Drawn from the Previous Literature Studies presenting simulations of the financial returns to renting and owning make a convincing case that in many markets over many periods of time and under a variety of assumptions renting ought to support greater wealth accumulation than owning. However, as virtually all of the panel studies document, in practice owning has consistently been found to be associated with greater increases in wealth even after controlling for differences in household income, education, marital status, starting wealth, inheritances, and other factors. Importantly, these same studies also consistently find that owning has a positive effect on wealth accumulation among both lower-income households and minorities, although the gains are smaller than for higher-income households and whites generally. Housing wealth among lower-income and minority households also often accounts a substantial share of total wealth for these groups. On the other hand, renters in these same demographic groups are consistently found to accrue little to no wealth over time. How can we reconcile the findings from simulation studies that renting should often be more financially advantageous than owning with the findings from the analysis of panel surveys that unambiguously find owning to be more favorable? One explanation may be that behavioral issues play 24 a key role. Efforts to save for a downpayment lead to a large jump in wealth that is then further supported by at least modest appreciation and some pay down of principal over time. Renters may have the opportunity to accrue savings and invest them in higher yielding opportunities but lack strong incentives and effective mechanisms for carrying through on this opportunity. There is also likely some degree of selection bias at work in who becomes a homeowner. While studies do control for income, education, marital status and other factors that would contribute in differences in the ability to save, there are likely differences in motivation and personal attributes that are related to both savings practices and whether someone becomes an owner. While controls included in studies to capture this effect have not diluted the association between homeownership and increases in wealth, this may simply reflect the challenge of capturing these difficult to measure factors. Studies using panel surveys may also make the benefits of homeownership appear more assured than they actually are by not fully capturing the impact of failed attempts at owning on changes in wealth. Studies to date have focused on measuring homeownership as the number of years spent as a homeowner, which does not distinguish between short sustained spells of owning from similar periods of owning that end in foreclosure or other financial distress. So while homeownership on average may increase wealth, it is undoubtedly the case that for some share of households owning a home had a negative impact on their balance sheet. Finally, the studies reviewed here may also not fully reflect changes that have occurred over time in both market conditions and household behavior. Most of the studies cited reflect experiences as owners during the 1980s and 1990s and so do not capture the market dynamics that began in the late 1990s but came to full bloom during the boom years of the 2000s, including the much greater availability of and appetite for high loan-to-value loans, higher cost loans, sharp swings in house prices, and much higher risks of default even before the national foreclosure crisis began. The next section turns to an analysis of data from the 2000s to examine whether findings about homeownership's positive association with wealth accumulation held over this period, particularly for low-income and minority households who were most likely to have used high cost mortgage products. Experience with Homeownership and Wealth Accumulation through the Boom and Bust Given the substantial changes in the availability, cost and terms of mortgage financing that began in the 1990s and accelerated through the mid-2000s and the accompanying boom and bust in home prices, there is good reason to believe that the experience of homeowners in accumulating wealth over the last decade has been substantially different from what is documented in much of the existing 25 literature for earlier periods. In this section of the paper we present information on wealth accumulation through homeownership during the housing market boom and bust of the 2000s. In the first section, we present findings from the tri-annual Survey of Consumer Finance (SCF) to present a high level picture of the contribution of homeownership to household balance sheets over time. The SCF also provides insights into how a greater tendency both to use high loan-to-value (LTV) loans to purchase homes and to take cash out through refinancing may have reduced wealth associated with homeownership. While the SCF does document the substantial decline in housing wealth following the bust, it also shows that, despite these losses, average homeownership wealth is generally higher than it was in the mid-1990s and continues to represent a substantial portion of household wealth for minorities and lower-income households. The SCF also shows that while the degree of leverage in the housing market showed a marked increase in the years following the Tax Reform Act of 1986, the distribution of LTVs did not change a great deal between the mid 1990s and the housing boom years. However, the crash in housing prices did push LTVs to historic highs. We then turn to an analysis of the PSID for the period from 1999 to 2009 to examine how homeownership spells contributed to trends in household wealth over this period. While house prices grew substantially for much of this period, it also captures most of the decline in prices as well. Whereas previous studies have focused solely on how each additional year of homeownership contributes to household wealth, we are also interested in assessing how failed attempts at homeownership affect wealth to assess the downside risks of owning as well. We find that on average homeownership's contribution to household wealth over this period was remarkably similar to that found in earlier periods. The results also confirm previous findings that while lower-income households and minorities realized lower wealth gains from owning, on average these gains were positive and significant. The results also show that a failure to sustain homeownership is associated with a substantial loss of wealth for established owners, although those who made a failed transition from owning to renting are no worse off financially than those who remained renters over the whole period. Thus, despite the many ways in which market conditions over this period might have been expected to undermine homeownership's wealth building potential, our analysis of the PSID finds that owning maintained a strong association with improvements in wealth over the decade from 1999 to 2009. Long-Run Trends in Housing Wealth and Mortgage Debt The sharp rise in home prices in many parts of the country is reflected in the substantial increase in average real housing equity among homeowners, roughly doubling (a gain of 96 percent) between 26 1995 and 2007 among all homeowners (Table 1). The gains were nearly as large among African- Americans (88 percent) and even larger among Hispanics (123 percent), although generally lower among households in the bottom two income quartiles where home equity increased by only 56 and 42 percent, respectively. The loss in housing equity between 2007 and 2010 was substantial, erasing 26 percent of home equity on average for all homeowners and taking back much of the gains made since 2001 for most groups. Mirroring their larger gains during the boom, Hispanics suffered the greatest loss of housing wealth, dropping by nearly half. Across income groups the declines were more moderate among those in the bottom half of the income distribution. But despite these substantial losses, average real home equity in 2010 was still higher on average than in 1995 for all of the groups shown, and in many cases considerably higher. Whites and those in the highest income quartile had the largest gains, with average home equity up by 51 percent and 78 percent respectively. African-Americans and the lowest income quartile also maintained substantial gains of 39 percent and 35 percent, respectively. Hispanics and those in the middle income quartiles made the least progress, with average home equity up by only 12 to 18 percent. Throughout this period the share of net wealth accounted for by home equity among all homeowners fluctuated between 22 and 29 percent, with much of the movement due to changes in non-housing net wealth. Between 1989 and 1998 home equity's share of average wealth fell from 29 to 22 percent as the stock market boomed while home values languished. Between 1998 and 2007 home equity's share of net wealth rose to 25 percent as the stock market absorbed the dot com bust while housing prices soared. Between 2007 and 2010 losses in housing wealth outpaced losses in other financial assets so housing's share of wealth fell back to 22 percent. Thus, despite the significant growth in housing equity in the first half of the 2000s it never came to account for an outsized portion of household net wealth among all homeowners.

Read the attached text, and then answer the question that follows using only details from the context provided. You will NOT refer to outside sources for your response. Based on the text above, what factors can contribute to wealth accumulation through homeownership? Introduction In many respects, the notion that owning a home is an effective means of accumulating wealth among low-income and minority households has been the keystone underlying efforts to support homeownership in recent decades. The renewed emphasis on boosting homeownership rates as a policy goal that arose in the early 1990s can be traced in no small part to the seminal work by Oliver and Shapiro (1990) and Sherraden (1991) highlighting the importance of assets as a fundamental determinant of the long-run well-being of families and individuals. The efforts of these scholars led to a heightened awareness of the importance of assets in determining life's opportunities, enabling investments in education and businesses, providing economic security in times of lost jobs or poor health, and passing on advantages to children. Assessments of differences in asset ownership placed particularly emphasis on the tremendous gaps in homeownership rates by race/ethnicity and income and the importance of these gaps in explaining differences in wealth. In announcing their own initiatives to close these homeownership gaps, both President Clinton and President Bush gave prominent attention to the foundational role that homeownership plays in providing financial security (Herbert and Belsky, 2006). But while faith in homeownership's financial benefits are widely subscribed to, there have long been challenges to the view that owning a home is necessarily an effective means of producing wealth for lower-income and minority households. In 2001 the Joint Center for Housing Studies hosted a symposium with the goal of "examining the unexamined goal" of boosting low-income homeownership (Retsinas and Belsky, 2002a). The general conclusion that emerged from this collection of papers was that lower-income households do benefit from owning homes, although this conclusion was subject to a variety of "caveats and codicils" (Retsinas and Belsky, 2002b, page 11). A few of these caveats related to whether financial benefits were likely to materialize, with papers finding that all too commonly homebuyers sold their homes for real losses while alternative investments offered higher returns (Belsky and Duda, 2002; Goetzmann and Speigel, 2002). In perhaps the most comprehensive critique of the policy emphasis of fostering low-income homeownership, Shlay (2006) reviewed existing scholarly evidence to cast doubt on the likelihood that either the financial or social benefits of owning would be realized. These criticisms have only grown louder in the aftermath of the housing bust, as trillions of dollars in wealth evaporated leaving more than 10 million homeowners owing more than their homes are worth and leading to more than 4 million owners losing their homes to foreclosure (Joint Center for Housing Studies, 2012; Kiviat, 2010; Li and Yang, 2010; Davis, 2012). Many of the criticisms raised about 1 the financial risks of homeownership are not new, but the experience of the last five years has certainly given new impetus to these arguments. But there are also concerns that changes in the mortgage market and in consumer behavior may have exacerbated these risks, increasing the odds that owners will, at best, be less likely to realize any financial gains from owning and, at worse, face a heightened risk of foreclosure. The goal of this paper is to reassess in the light of recent experience whether homeownership is likely to be an effective means of wealth creation for low-income and minority households. Has the experience of the last decade proven the arguments of earlier critics of homeownership? Have changes in the market affected whether these benefits are likely to be realized? The paper takes three approaches to address these questions. We begin by presenting a conceptualization of the risks and rewards of homeownership as a financial choice, with a particular eye toward whether the odds of a beneficial outcome are lower for lower-income and minority owners. This review also assesses whether recent experience has altered this calculus-as opposed to just raising our awareness of the proper weighting of the likelihood of realizing the benefits while sidestepping the risks. Next, we review the existing literature examining the financial benefits of owning a home, including both studies simulating the returns to owning and renting as well as studies using panel surveys to track actual wealth accumulation among owners and renters. Finally, we examine data from the Survey of Consumer Finance (SCF) and the Panel Study of Income Dynamics (PSID) covering the last decade to assess how owning a home has been associated with changes in household financial balance sheets over this period. To preview our conclusions, we find that while there is no doubt that homeownership entails real financial risks, there continues to be strong support for the association between owning a home and accumulating wealth. This relationship held even during the tumultuous period from 1999 to 2009, under less than ideal conditions. Importantly, while homeownership is associated with somewhat lower gains in wealth among minorities and lower-income households, these gains are on average still positive and substantial. In contrast, renters generally do not see any gains in wealth. Those who buy homes but do not sustain this ownership also do not experience any gains in wealth, but are generally left no worse off in wealth terms than they were prior to buying a home-although of course there may still be substantial costs from these failed attempts at owning in terms of physical and mental health as well as future costs of credit. We conclude that homeownership continues to represent an important opportunity for individuals and families of limited means to accumulate wealth. As such, policies to support homeownership can be justified as a means of alleviating wealth disparities by extending this 2 opportunity to those who are in a position to succeed as owners under the right conditions. The key, of course, is to identify the conditions where lower-income and minority households are most likely to succeed as owners and so realize this potential while avoiding the significant costs of failure. Assessing the Financial Risks and Rewards of Homeownership Before turning to evidence about the financial returns to homeownership, it is helpful to start by framing the arguments about why homeownership is thought to be an effective means of generating wealth as well as the counter arguments about why these benefits may not materialize, particularly for lower-income and minority homeowners. We then consider how changes in mortgage markets and consumer behavior may have altered the likelihood that owning will lead to financial gains. This framing helps provide a basis for interpreting the findings from the following two sections of the paper that examine evidence about the association between homeowning and wealth accumulation. The Potential Financial Benefits of Owning The belief that homeownership can be an important means of creating wealth has its roots in five factors. First, the widespread use of amortizing mortgages to finance the acquisition of the home results in forced savings as a portion of the financing cost each month goes toward principal reduction. While modest in the early years of repayment, the share of the payment going toward principal increases over time. For example, assuming a 30-year loan with a 5 percent interest rate, a homeowner will have paid off about 8 percent of the mortgage after 5 years, 19 percent after 10 years, and nearly a third after 15 years. Assuming a household purchases a home in their early 30s and keeps on a path to pay off the mortgage over a thirty-year period, these forced savings will represent a sizable nest egg when they reach retirement age. In addition, an often overlooked aspect of forced savings associated with homeownership is the accumulation of the downpayment itself, which often entails a committed effort to accumulate savings in a short period. Second, homes are generally assumed to experience some degree of real appreciation over time, reflecting increased overall demand for housing due to growth in both population and incomes against a backdrop of a fixed supply of land located near centers of economic activity. Shiller (2005) has been the most notable critic of this point of view, arguing that over the very long-run real house prices have only barely exceeded inflation. Lawler (2012), however, has argued that Shiller's house price estimates and measures of inflation result in an underestimate of real house price growth. Analysis of trends in real house prices across a range of market areas support the conclusion that these trends 3 reflect a complex interaction of supply and demand factors in local markets that defy simple categorization (Capozza et al. 2002, Gallin, 2006). At a national level the Federal Housing Finance Agency house price index indicates that between 1975 and 2012 the compound annual growth rate in house prices has exceed inflation by 0.8 percentage points. Even at a modest rate of increase, the compounding of these returns over a longer period of time can be produce substantial increase in real home values. Assuming just a 0.8 percent annual real increase in house values over 30 years an owner will experience a real gain of about 26 percent in the overall house value. The use of financing can further leverage these returns. A homebuyer with a modest downpayment gets the benefit of increases in the overall asset value despite their small equity stake. While the cost of financing can create a situation of negative leverage if the increase in house values is lower than the cost of financing (so that the financing costs exceed the increase in the asset value), this risk diminishes over time as the value of the house compounds while the debt payment is fixed. Through leverage, the rate of return on an investment in a home can be substantial even when the increase in house values is modest. Consider the case where a buyer puts down 5 percent and the house appreciates at 4 percent annually. After 5 years the home will have increased in value by nearly 22 percent or more than 4 times the initial 5 percent downpayment. Even allowing for selling costs of 6 percent, this would represent an annualized return of 31 percent on the owner's initial investment. Due to leverage, even nominal increases in home values that do not exceed inflation can result in real returns. In the above example, if inflation matched the 4 percent growth in home prices, the owner would still have earned a substantial real return on their initial investment. Federal income tax benefits from owning a home can also be substantial. The ability to deduct mortgage interest and property taxes is the most apparent of these benefits. Taxpayers who are able to make full use of these deductions receive a discount on these portions of ongoing housing costs at the taxpayer's marginal tax rate, ranging from 15 percent for moderate income households up to 39 percent for the highest tax bracket. In addition, capital gains on the sale of a principal residence up to $250,000 for single persons and $500,000 for married couples are also excluded from capital gains taxation, which is currently 15 percent for most households and 20 percent for the highest income bracket.1 1 An additional tax benefit that is often overlooked is the fact that while owner occupants benefit from the use of their home as a residence they do not have to pay any tax on these benefits, referred to as the implicit rental income from the property (that is, the rent one would have to pay to occupy the home) (Ozanne, 2012). The loss of revenue to the U.S. Treasury from this exclusion is substantial, outweighing the costs of the mortgage interest deduction. 4 Finally, owning a home provides a hedge against inflation in rents over time. Sinai and Souleles (2005) find that homeownership rates and housing values are both higher in markets where rents are more volatile, indicating the value placed on being able to protect against rent fluctuations. Under most circumstances, mortgage payments also decline in real terms over time, reducing housing costs as a share of income. For long-term owners, this can result in fairly substantial savings in the out of pocket costs for required for housing. Assuming a fixed rate mortgage, inflation of 3 percent, 1 percent growth in both real house prices and the costs of property taxes, insurance and maintenance, real monthly housing costs would decline by about 10 percent after 5 years, 15 percent after 10 years, and 30 percent by the last year of the mortgage. Once the mortgage is paid off, the out of pocket costs of owning in real terms are less than half the payments made at the time of purchase. Housing costs for renters, in contrast, would be expected to keep pace with inflation in housing prices. The Potential Financial Risks of Owning Combined, the financial benefits outlined above can fuel significant wealth accumulation. But as the last few years have made painfully clear, the financial benefits associated with owning a home are not without risk. To begin with, house prices can be volatile. That was certainly the case in the wake of the housing bust, as nominal prices fell nationally by some 25 percent or more (depending upon the specific price index used), with the hardest hit markets experiencing declines of more than 40 percent. Almost no area of the country was spared from some degree of decline. According to the FHFA index, nominal prices fell in every state with the exception of North Dakota. But while recent experience is notable for the breadth and depth of price declines, there are other examples of fairly significant price declines over the last few decades, including declines of between 10 and 20 percent in some Oil Patch states in the 1980s and in New England, California and Hawaii in the early 1990s. There are also a number of markets where house prices trends have historically been more stable, but in these areas long-run real price increases have either not kept pace with inflation or have been modest. House price growth has been particularly weak in a number of markets in the Midwest and South where population and income growth have been low. Based on long-run state level indexes from FHFA, between 1975 and 2012 there were 10 states in these regions where the compound annual growth in house prices did not exceed general price inflation. Even before the bust, homeowners in these markets did not have the benefit of real growth in house prices over the long term. In nine other states house price growth did beat inflation, but by less than 0.25 percent on an annual basis. Thus, in about two-fifths of states real house price growth was either non-existent or trivial. At the other 5 extreme there were 17 states, mostly along the Pacific coast and in the Northeast that experienced real house price growth of more than 1 percent, including 5 states that exceeded 2 percent. There are also peculiar aspects of owning a home that further exacerbate the financial risks of these investments. Homeowners make a significant investment in a specific location and cannot diversify the risk of home price declines by spreading this investment across assets or across markets. Homes values are also high relative to incomes and so account for a large share of household wealth. Wolff (2012) reports that in 2010 the value of the principal residence accounted for two-thirds of total wealth among households in the middle three quintiles of the wealth distribution. With so much wealth tied up in one asset, homeowners are particularly vulnerable to changes in home values. The use of debt financing for a large share of the purchase further magnifies these risks, with even small drops in prices wiping out substantial shares of homeowner equity. Indeed, at the height of the housing bust the number of households underwater on their mortgages was estimated by CoreLogic to have exceeded 11 million while Zillow placed the number closer to 15 million. When assessed purely on the basis of real growth in values over time, housing also compares poorly to the returns offered by investments in diversified portfolios of stock or bonds. Geotzmann and Speigel (2002) compare the change in home prices in 12 market areas between 1980 and 1999 to a range of alternative investments and find that housing was consistently dominated as an investment asset by all of the financial alternatives considered, leading them to conclude that it is "surprising that housing continues to represent a significant portion of American household portfolios" (page 260). However, Flavin and Yamashita (2002) take a more expansive view of the returns on housing investments by including the value derived from occupying the unit, the use of financial leverage, and the ability to claim income tax deductions. This fuller treatment of housing's returns finds that the average rate of return was slightly below returns for investments in stocks, but the variance of these returns were also lower and so somewhat less risky. Still, even if the returns to housing are deemed to be competitive with alternative investments the concern remains that it accounts for an excessive share of low-wealth household's portfolios. Housing investments are also handicapped by high transaction costs associated with buying and selling these assets. Home buyers face fees for mortgage origination, title search and insurance, state and local taxes, home inspections, and legal fees, all of which can add up to several percentage points of the home value. Real estate broker commissions typically also command 6 percent of the sales price. These high transaction costs can absorb a significant share of home price appreciation from the first few years of occupancy. Given these high costs, home owners who are forced by circumstances to move 6 within a few years of buying will face the risk of loss of at least some share of their initial investment even if home values have risen modestly. The need to maintain the home also imposes financial risks on owners. While routine maintenance can keep both the physical structure and the home's major systems in good working order, major investments are periodically needed, such as painting the exterior or replacing the roof or heating system. These projects incur high costs that may be difficult for owners to afford. While owners may have the opportunity to plan for these investments over time, in some cases a system will fail with little warning and produce an unexpected cost that the owner cannot afford, creating a financial strain that in the most extreme cases can jeopardize the ability to maintain ownership. Finally, the financial costs of failing to sustain homeownership are high-in addition to the traumatic impacts that foreclosures can have on the health and psychic well-being of the owner (Carr and Anacker, 2012). Owners who default on their mortgage will not only lose whatever equity stake they had in the home, they are also likely to deplete their savings in a bid to maintain ownership and suffer significant damage to their credit history making it difficult and costly to obtain credit for several years to come. Factors Contributing to Wealth Accumulation Through Homeownership Whether and to what extent a homebuyer will realize the potential benefits of owning while avoiding succumbing to the risks depends on a complex set of factors. Herbert and Belsky (2006) present a detailed conceptual model of the factors that contribute to whether homeownership produces wealth over the life course, which is briefly summarized here. The most obvious factor is the timing of purchase relative to housing price cycles. The recent boom and bust in house prices presents a prime example. Homebuyers who bought in the early 2000s were poised to benefit from the massive run-up in prices that occurred in many markets, while those that bought in the mid 2000s entered just in time for the historic freefall in prices that followed. While other price cycles in recent decades may not have been as dramatic, the consequences of buying near troughs or peaks on wealth accumulation would have been similar. Belsky and Duda (2002) examined data on repeat sales in four market areas between 1982 and 1999 and found that roughly half of owners who bought and sold their homes within this time period failed to realize gains that beat inflation after assuming a 6 percent sales cost (although most did earn a return in nominal terms). Whether owners realized a positive return depended strongly on where in the housing price cycle they bought and sold their homes. 7 Belsky and Duda (2002) conclude that "although the golden rule of real estate is often cited as location, location, location, an equally golden rule is timing, timing, timing" (Page 223). Their conclusion points to another critical factor in how likely a home is to appreciate in value - in what market and in which specific neighborhood the home is located. As noted above, there have been sizeable differences across market areas in long-term house price trends, with areas along the coasts experiencing real gains of one percent or more over the last several decades while areas in the Midwest and South have had little or no gains. But there are also substantial variations in price trends across neighborhoods within a single market (for reviews of this literature see Herbert and Belsky, 2006; Dietz and Haurin, 2003; and McCarthy, Van Zandt and Rohe, 2001). Whether a household bought a home in Boston or Cleveland is an important factor in the returns realized, but so is whether the home was in a desirable area or a declining neighborhood. The terms of financing used to buy the home also matter. Higher interest rates lower the share of payments that are devoted to principal reduction in the early years of repayment, slowing wealth accumulation. The higher monthly costs of the mortgage also erode the ability of the household to meet other expenses and to save on an ongoing basis as additional interest payments over the life of the mortgage can be substantial. For example, over a thirty-year term a loan for $150,000 at 7 percent interest will require $69,000 more in interest payments than a 5 percent loan. Higher origination fees also sap savings, reducing the quality and size of home that is affordable and lowering the rate of return on housing investments. Choices about refinancing over time can also exert a strong influence on wealth accumulation. Taking advantage of declines in mortgage interest rates to reduce financing costs can save owners hundreds of dollars each month, and tens of thousands over the life of a mortgage-although continually resetting the term of the mortgage will reduce opportunities for forced savings. On the other hand, refinancing to take cash out of the property can erode wealth accumulation, particularly if the extracted funds are used to finance consumption rather than investments in the home, education, business or financial opportunities. Wealth accumulation will be further undermined if the new loan comes with high fees and higher interest rates. Of course, the ability to tap housing wealth as a buffer against income shocks is one of the virtues of developing this cushion, but using home equity to finance an unaffordable lifestyle is an unsustainable path. A host of other factors come into play in determining how much housing wealth is realized over the span of a lifetime. For example, buying higher valued homes-if successful-can produce more wealth both through forced savings and by earning returns on a higher valued asset. By the same 8 means, those who trade up to more expensive homes over time may also accrue greater housing wealth. The age at which a first home is purchased can also be significant, giving the household a longer period to accumulate wealth. Of course, the quality of the home purchased and the owner's ability to maintain it will also affect both ongoing maintenance costs and how much the home appreciates over time. But arguably the most fundamental factor-the true golden rule of how to accumulate wealth. through homeownership-is whether ownership is sustained over the long term. Housing booms aside, many of the financial benefits are slow to accumulate, including the slow build up of forced savings, the compounding of values at low appreciation rates, and the decline in monthly housing costs in real terms over time. The expression "time heals all wounds" may also be applicable to many of homeownerships most critical risks. The losses associated with buying near the peak of a price cycle will diminish over time as owners benefit from the next upswing in prices. And even in areas whether real growth in house prices does not occur or is limited, over the long term owners will still amass some degree of wealth through paying off the mortgage and as a result of savings from lower housing costs. On the flip side, a failure to sustain homeownership-particularly when the end result is a foreclosure-will wipe out any accrued wealth and bring additional costs in the form a damaged credit history that will incur further costs over time and limit opportunities to buy another home in the near term. To some degree whether ownership is sustained will depend on choices that owners make over time - including whether the home they buy is affordable, whether they make prudent choices about refinancing, and whether they maintain the home to avoid larger home repair bills. But whether owning is sustained also will depend on whether the household can weather any number of significant events that can fundamentally alter their financial circumstances, such as loss of a job, a serious health problem, or change in the family composition due to the birth of a child, death, divorce, or the need to care for a parent or relative. Over the course of a lifetime, these events are likely to befall most everyone. Whether homeownership can be sustained in the wake of these events will depend on the ability of the household to adjust to their changed circumstances and whether they have enough available savings to cushion the blow. Impediments to Wealth Creation among Lower-Income and Minority Homeowners Up to this point the discussion presented has considered homeownership's financial risks and rewards in a general sense. But the concern of this paper is specifically with the potential for homeownership to serve as an effective means of wealth accumulation for lower-income and minority 9 households. How are the odds of generating wealth as a homeowner likely to differ for these households?? In keeping with the fundamental importance of sustained homeownership to accumulate wealth, the chief concern is that these groups of homebuyers face a more difficult time in maintaining ownership. Studies analyzing panel data to document homeownership spells among first-time buyers consistently find that low-income and minority owners have a lower probability of maintaining homeownership for at least five years. In an analysis of the National Longitudinal Survey of Youth (NLSY) from 1979 through 2000 Haurin and Rosenthal (2004) find that ownership is less likely to be sustained among both these groups. Specifically, only 57 percent of low-income buyers were found to still own their first home five years later, compared to 70 percent of high-income owners (with income categories defined by income quartiles at age 25). First homeownership spells were also found to be much shorter for minorities, averaging 6.5 years among whites, compared to 4.4 years for blacks and 5.4 years for Hispanics. In an analysis of the PSID covering the period from 1976 through 1993 Reid (2004) had similar results, with only 47 percent of low-income owners still owning their first homes 5 years later compared to 77 percent of high income owners (with incomes here defined based on average income in the years prior to homeownership compared to area median incomes). Reid further found that minorities had a harder time staying in their first home, with 42 percent of low-income non-whites still owning after five years compared to 54 percent of low-income whites. While these results raise clear concerns about the high risk of failed homeownership among these groups, the focus on a single homeownership spell may overstate the extent to which homeowning is not sustained in the long run. Haurin and Rosenthal (2004) also examine subsequent tenure experience in their panel and find that the share of households that return to owning a second time is very high for both whites and minorities. Over the 21 year period in their panel, 86 percent of whites who ever bought a home either never returned to renting or regained owning after a subsequent spell as a renter, with only slightly lower rates for blacks (81 percent) and Hispanics (84 percent). However, they do find that minorities spend more years in their intervening spells as renters, which reduces the overall amount of time they can accumulate benefits from owning. Another critical difference in the financial returns to owning for low-income households is that the ability to deduct mortgage interest and property taxes from federal taxable income may be of little or no value. In order to benefit from these tax provisions, the amount of available deductions must 2 Galster and Santiago (2008) provide a useful framing of this issues and a comprehensive review of the relevant literature. 10 exceed the standard deduction, which stood at $5,950 for individuals and $11,900 for married couples in 2012. For taxpayers with lower valued homes, particularly married couples, the costs of mortgage interest and property taxes even when added to other deductions for state taxes and charitable contributions, may not greatly exceed the standard deduction. In addition, the value of these deductions depends on the taxpayer's marginal tax rate, which will lower for low- and moderate-income households. In fact the share of the total value of the mortgage interest deduction going to moderate income households is fairly small. According to estimates from the Joint Committee on Taxation (2013), only 3 percent of the total deductions went to filers with incomes under $50,000, 9 percent to those with incomes between $50,000 and $75,000, and 11 percent to those with income between $75,000 and $100,000, leaving 77 percent of the benefit going to those earning above $100,000. To the extent that these tax benefits swing the financial scales in favor homeownership, this tilting of the calculus is not very evident for low- and moderate-income tax filers. There are also systematic differences in mortgage terms and characteristics by income and race/ethnicity that can also affect the financial returns to owning. The development of the nonprime lending industry that began in the 1990s and came to full blossom during the housing boom produced much greater variation in mortgage terms and pricing than had previously been evident. A fairly extensive literature has documented the greater prevalence of subprime lending among minorities and, to a lesser extent, low-income borrowers and communities (see, for example, Bradford, 2002; Calem, Gillen and Wachter, 2004; Apgar and Calder, 2005; Avery, Brevort, and Canner, 2007; Belsky and Richardson, 2010). As described above, higher costs of financing can significantly reduce the financial benefits of owning. While the expansion of financing options beyond a "one size fits all who qualify" approach to lending has the potential to extend homeownership opportunities to a greater range of households, there is significant evidence that the cost of credit was often higher than risk alone would warrant. Bocian, Ernst and Li (2008) present perhaps the most compelling evidence through an analysis of a large data set on nonprime loans that documents a wide range of risk measures, including credit scores as well as income and race/ethnicity. They find that even after controlling for observable differences in credit quality both blacks and Hispanics were significantly more likely to obtain high- priced mortgages for home purchase, while blacks were also more likely to obtain higher-priced refinance loans. These higher costs of borrowing not only limit the wealth producing capacity of homeownership, they also increase the risk of failing to sustain homeownership. In fact, Haurin and Rosenthal (2004) find that a 1 percentage point increase in the mortgage interest rate increases the rate of homeownership termination by 30 percent. 11 Low-income and minority borrowers are also less likely to refinance when interest rates decline. In an analysis of loans guaranteed by Freddie Mac during the 1990s Van Order and Zorn (2002) find that low-income and minority borrowers were less likely to refinance as interest rates fell. Their analysis also found that once borrower risk measures and loan characteristics were taken into account there were no remaining differences in refinance rates by income-although this just indicates that refinancing may be constrained by credit factors. Minorities, on the other hand, still had lower rates of refinancing even after controlling for these factors, suggesting that there were impediments to refinancing by these borrowers that were in addition to measurable credit factors. Nothaft and Chang (2005) analyze data from the American Housing Survey (AHS) from the late 1980s through 2001 and also find that minority and low-income owners were less likely to refinance when interest rates declined. These authors use their results to estimate the foregone savings from missed refinance opportunities, which are more than $20 billion each for black and low-income homeowners. To the extent that low-income and minority homebuyers may be more likely to purchase homes in poor condition they are also exposed to greater risks of high costs of maintenance and repair. Herbert and Belsky (2006) find that compared to whites, black and Hispanic first-time homebuyers were more likely to buy homes that were moderately or severely inadequate as characterized by the AHS- 6.5 percent for blacks and 8.8 percent for Hispanics compared to 4.3 percent among whites. A similar gap was also evident between low- and high-income households. While there has been little study of the incidence of unexpected home repair needs, a study by Rohe and his colleagues (2003) of participants in homeownership counseling programs found a fairly significant incidence of the need for unexpected repairs. Roughly half of 343 recent homebuyers reported that they had experienced a major unexpected cost in the first few years after buying their home, with the most common problem being a repair to one of the home's major systems. Finally, there are also concerns that lower-income households and minorities may be more likely to purchase homes in neighborhoods with less potential for house price appreciation. This is a particularly salient issue for minorities given the high degree of residential segregation by race and ethnicity that continues to be evident in the US. However, Herbert and Belsky (2006) present a detailed review of this literature and conclude that "taken as a whole the literature indicates that there is no reason to believe that low-value segments of the housing market will necessarily experience less appreciation than higher-valued homes. In fact, at different points in time and in different market areas, low-valued homes and neighborhoods have experienced greater appreciation rates. Although the opposite is also true." (Page 76) The evidence about differences in appreciation rates by neighborhood 12 racial composition is less definitive. Here Herbert and Belsky (2006) conclude that "it does appear that homes in mostly black areas may be less likely to experience appreciation, but this conclusion is tempered by the small number of studies and the fact that they mostly analyzed trends from the 1970s. and 1980s, which may no longer be relevant" (page 77). Findings by Boehm and Schlottmann (2004) regarding differences in wealth gains from homeownership by race and income are instructive in this regard. They find that over the period from 1984 to 1992 there was little difference in appreciation rates in the specific neighborhoods where minorities and low-income households lived. Instead, they found that differences in housing equity accumulation were tied to the lower valued homes and the shorter duration of ownership for lower- income and minority households. Thus, differences in appreciation rates may be less of a concern in whether housing leads to wealth accumulation than these other considerations. Re-assessing the Calculus of Wealth Accumulation through Homeownership As the above review has shown, there were significant concerns about the risks of homeownership as an investment well before the housing bubble burst. For critics of homeownership as a wealth building tool the experience of the housing bust was in many respects a confirmation of their fears. Still, there were several markets developments during the boom years that magnified these preexisting risks. Most notably there was a marked increase in the prevalence of riskier mortgages, including those calling for little or no documentation of income, adjustable rate loans that exposed borrowers to payment shocks from the expiration of initial teaser rates or reduced payment options, allowances for higher debt to income ratios, and greater availability of loans for borrowers with very low credit scores. Downpayment requirements also eased as loan-to-value ratios (LTVs) of 95 percent or more became more common and borrowers also used "piggyback" second mortgages to finance much of the difference between the homes' value and a conforming first mortgage at an 80-percent LTV. Not unrelated to the greater availability of mortgage credit, house prices also exhibited much greater volatility than in the past, with a dramatic increase in prices that greatly outpaced trends in both incomes and rents and belied an unsustainable bubble. The greater availability of credit also increased the opportunity for lower-income households to miss-time the market. Belsky and Duda (2002) found that during the 1980s and 1990s lower-valued homes were less likely to be transacted around market peaks, so buyers of these homes were less likely to buy high and sell low. They speculated that this was due to the natural affordability constraints that took hold as markets peaked. But during the boom of 13 the 2000s lower-valued homes experienced greater volatility in prices, arguably reflecting much greater credit availability at the peak than was true in past cycles (Joint Center for Housing Studies, 2011). However, there are good reasons to believe-or certainly to hope-that the conditions that gave rise to this excessive risk taking and associated housing bubble will not be repeated any time soon. The Dodd-Frank Act includes a number of provisions to reduce the degree of risk for both borrowers and investors in the mortgage market. The Qualified Mortgage (QM) is aimed at ensuring that borrowers have the ability to repay mortgages by requiring full documentation of income and assets, setting tighter debt to income standards, and excluding a variety of mortgage terms that expose borrowers to payment shocks. The Qualified Residential Mortgage (QRM) is aimed at ensuring greater protections for investors in mortgage backed securities by requiring the creators of these securities to retain an interest in these investments if the loans included in the loan pool do not conform to certain risk standards that essentially mirror those of the Qualified Mortgage. Dodd-Frank also established the Consumer Financial Protection Bureau to fill a gap in the regulatory structure by creating an agency charged with looking out for consumers' interests in financial transactions. Beyond these regulatory changes, there is also a heightened awareness of the risks of mortgage investments on the part of private sector actors who have suffered significant financial losses with the bursting of the housing bubble. Regulatory changes aside, these private actors are unlikely to embrace riskier lending any time soon. The Federal Reserve and other federal regulators are certainly more attuned to the possibility of a bubble in housing prices and so are more likely to act in the event that signs of a bubble re-emerge. But even in the absence of the excessive risks of the last decade, homeownership will remain a risky proposition. Thus, at best, we may return to the market conditions that existed prior to the boom and the real risks that these conditions posed for investments in owner-occupied housing. In that regard, an assessment of experience in wealth creation through homeownership prior to the boom is relevant for what we might expect in the future. On the other hand it does seem likely-and arguably even desirable given how tight credit has become-that some greater degree of risk taking will emerge to make credit available to the many lower-income and lower-wealth households that would like to own a home. In fact, the QM standard of a total debt-to-income ratio of up to 43 percent does curtail the higher levels that became evident during the boom, but this cutoff still represents a liberalization from standards for conventional mortgages that prevailed in the 1990s. There may also have been a shift in consumer attitudes toward mortgage debt, with fewer households seeking to pay off mortgages over time and thus exposing themselves for longer periods to the risks associated with these leveraged investments. Over time, as 14 conditions return to normal and the market adjusts to new regulatory structures, we are likely to see mortgages originated outside of the QM and QRM boxes. In that regard, an assessment of the experience of homeowners through the boom and bust is instructive as a stress test of how likely homeownership is to build wealth under more extreme market conditions. The next two sections of the paper look to assess homeownership's potential for wealth building from these two perspectives. First by presenting a review of the literature assessing homeownerships' association with wealth building prior to the 2000s and then by analyzing data from the last decade to examine how homeownership was associated with changes in wealth through the turbulent conditions of the 2000s. Review of Previous Studies Assessing the Financial Returns to Homeownership As the discussion up to this point has intended to illustrate, whether owning a home will lead to the accumulation of wealth is the result of complex set of factors related to the choices that households make in buying their home and how these choices interact with market conditions both at the time of purchase and over time. This complexity makes it quite difficult to assess whether in practice owning is likely to be an effective means of increasing a household's wealth. A further complicating factor is that there is a substantial selection bias in who becomes a homeowner, as there is reason to believe that those who are most secure in their financial condition and most inclined to save are more likely to become owners. For this reason, comparisons of the wealth profiles of owners and renters may not be able to attribute any observed differences solely to the influence of homeownership on the ability to accrue wealth. There are two broad classes of studies that have attempted to assess the financial benefits of homeownership in light of these challenges. One group relies on simulations that compare the theoretical costs and benefits of owning and renting under a variety of assumptions about market conditions and household choices. A key appeal of these studies is that they essentially remove concerns about selection bias by assuming otherwise identical households operate under a consistent set of decision rules. They can also isolate the influence of specific factors to shed light on the paths that are most likely to make owning or renting financially beneficial. But while these studies highlight the potential financial returns to owning and renting, they do not capture how households are likely to actually behave in these situations and so leave open the question of whether the potential returns of these tenure choices are likely to be realized in practice. 15 Another group of studies rely on panel studies that track households over time to examine how choices about owning and renting are correlated with changes in wealth. The findings from this type of analysis provide evidence of whether in practice owners are more likely to accrue wealth than renters and how this experience differs by income and race/ethnicity. Where the theoretical comparisons of owning and renting also generally focus on a single spell of homeownership - that is, the financial outcome associated with the period between buying and selling a single home - panel studies can track households through multiple transitions in and out of owning to assess outcomes from a series of tenure choices over time. The main drawback of these studies is the lingering concern that owners may be inherently different from renters in ways that observable household characteristics cannot capture. Some of these studies employ statistical methods to try to control for this selection bias, although it is doubtful that these controls can fully account for these differences. Both classes of studies provide important insights into the opportunities and drawbacks of homeownership as a means of increasing household wealth. When viewed as a whole the findings from both streams of research help paint a clearer picture of whether and how homeownership may help foster wealth creation. The sections that follow highlight key findings from each of these literature strands. Simulations of the Financial Returns to Owning and Renting Beginning with Mills (1990) there have been a number of studies that have simulated the financial returns to owning and renting under a variety of assumptions to identify whether and under what circumstances owning or renting is likely to be more financially beneficial (Capone, 1995; Belsky, Retsinas, and Duda, 2007; Rappaport, 2010; Beracha and Johnson, 2012). While the studies differ in important respects, the general approach is to compare the "all-in" costs of owning - including mortgage interest, property taxes, insurance, maintenance, and transaction costs along with offsetting gains in property value - to the costs of renting a comparable housing unit. Either implicit or explicit in these comparisons is that renters save and invest both the initial investment that owners make in buying their homes as well as any annual savings in housing costs. There are a host of assumptions that underlie these calculations, but among the most influential factors are the estimate of rents as a share of house value, the length of time the home is owned, the basis for simulating trends in house prices and rents over time, and the treatment of income tax benefits. The studies differ in fundamental ways related to the range of assumptions tested and the method for comparing returns to owning and renting and, as a result, individually reach somewhat 16 different conclusions about which tenure choice is likely to be preferred. But collectively the studies lead to some general conclusions about the relative financial merits of owning and renting. Perhaps the most fundamental conclusion from these studies that runs counter to the prevailing sense that homeownership is a powerful source of wealth is that under a variety of conditions renting is often more likely to be a better financial choice than owning. Belsky, Retsinas and Duda (2007) compare owning and renting in four different market areas chosen to represent different degrees of price appreciation and volatility over the period studied from 1983 through 2001. They focus on holding periods of 3, 5 and 7 years during their window of study and report the share of different holding periods where owning results in higher financial returns than renting. Overall they find that in only 53 percent of the 3-year holding periods would owning be preferred to renting. Increasing the holding period to 7 years-which allows for more time to work off the high transaction costs of buying and selling a home-only increases this proportion to 63 percent. Rappaport (2010) reaches a similar conclusion based on an analysis of national trends in market conditions between 1970 and 1999 and an assumed 10-year period of owning a home. He finds that owning a home unambiguously built more wealth in about half of the possible 10-year periods, renting was clearly better in another quarter and likely, but not unambiguously, preferred in the remaining periods. Finally, Beracha and Johnson (2012) come to a similar conclusion in an analysis of all possible 8-year holding periods given actual market conditions at both the national and regional level between 1978 and 2009. They find that between 65 and 75 percent of cases renting offered greater opportunities for accruing wealth than owning, depending on whether renters employing a more conservative or aggressive investment approach. In parsing the findings of these studies, there are several factors that are the critical drivers of the results. Perhaps the most obvious is the importance of the timing of home purchase relative to market cycles in prices and interest rates. Depending on the future course of prices, rents and interest rates one or the other tenure would be strongly preferred at different points in time. The importance of timing may be most clearly demonstrated in Belsky, Retsinas and Duda (2007) when they consider different holding periods among owners. In general, it would be expected that longer holding periods should favor owning as more time is allowed to overcome high transaction costs, pay down additional principal, and ride out price cycles. Instead, they find that in most markets the likelihood of owning being preferred to renting was little changed by the holding period as short holding periods offered the possibility of catching only the upswing in prices while longer holds made it more likely that owners would share in some portion of a downturn. Only in Chicago, which did not experience such dramatic swings in prices, were longer holding periods found to be much more likely to benefit owning. 17 Still, the issue of holding period is an important consideration. The analysis by both Mills and Capone solved for the holding period that was needed for owning to yield a higher return than renting on the assumption that longer holding periods would always favor homeownership. In his base case scenario Mills found a holding period of slightly longer than 7 years was needed for owning to be preferred. The more recent studies that have showed the importance of market timing either assumed a single fixed holding period of 8 to 10 years (as in Beracha and Johnson and Rappaport) or a range of relative short holding periods (as in Belsky, Retsinas and Duda). If owning does become more favorable over a longer period of time - for example, slightly longer than 8 to 10 years - these assessments would not capture this. In fact, many households move in and out of homeownership over time so a more complete assessment of the financial implications of tenure choice would take into account multiple homeownership spells. While one spell of owning may yield low returns, if homeowning is sustained or resumed then the household may yet benefit from the next upswing. Another important factor driving the findings are assumptions made about rents as a share of house value. This ratio is difficult to estimate both because of systematic differences in the nature of the owner and renter occupied stock and because market values and rents are hard to observe simultaneously. How much renters have to pay to rent a comparable home is obviously a key driver of financial outcomes as it determines how much they can save annually by renting, thereby adding to their wealth. Mills (1990) found that among the variables used in his simulation, his results were most sensitive to the ratio of rents to house values as a single percentage point change up or down leading to fluctuations in the required holding period from 3 to 23 years. Capone (1995) built on Mills study to examine the rent-versus-buy decision specifically for lower income households. He makes note of the importance of the rent-to-price ratio assumption and argues that Mills assumption of 7 percent was well below the ratios observed in low-cost segments of the market, where ratios of 10 to 12 percent were more reasonable. Under Capone's assumption that renters faced much higher rents he found that owners only needed to hold onto their homes for about 3 years for owning to be preferred. In contrast, Belsky, Retsinas and Duda rely on rent to price ratios is in the range of 5 to 7 percent, while the series used by Beracha and Johnson derived by Davis, Lehnert, and Martin (2008) appears to average about 5 percent. In both cases these assumptions are more favorable to renting than the assumptions used by either Mills or Capone. In recognition of the importance of this assumption, Rappaport structures his analysis to estimate the rent-to-price ratio that is the breakeven point between owning and renting. He then compares this estimate to what he feels is a plausible range for this ratio of 18 between 5 and 10 percent based on analysis of different market areas over time. At the higher end of this range owning would almost always be preferred, while the lower end leads to his conclusion that owning is clearly preferred to renting in only about half of the holding periods considered. In short, high or low values of this ratio can swamp other considerations, yet, as Rappaport demonstrates, pinning down actual values for this ratio is not an easy task. Several of the studies have examined the issue of whether tax benefits are important to whether owning makes more financial sense than renting. Mills assumes that owners can take full advantage of tax benefits at a 28 percent marginal rate. When he reduces the marginal rate to 15 percent he finds that owning is never preferred. Capone, though, demonstrates, that this knife edge does not hold if a higher rent to price ratio is assumed. In his base case analysis, owners are only assumed to benefit from tax benefits if they exceed the standard deduction and since he assumes a much more modest house in keeping with his focus on lower-income households, the tax benefits are essentially non-existent. As a result, reducing the tax benefits in his analysis does not change his conclusion that owning is a better financial choice even after only a few years. Belsky, Retsinas and Duda also examine the importance of tax benefits for lower-income owners. Like Capone, they adjust the value of tax deductions to account for the size of the home purchased and the amount of the standard deduction. They also find that tax benefits by themselves generally do not change the calculus of whether owning beats renting financially. So while tax benefits are an important factor among higher income households, as Mills found, it has little effect on the calculus for lower-income households. Despite getting limited benefits from tax breaks under a variety of circumstances Capone and Belsky, Retsinas and Duda find that lower-income households can fare better financially by owning. Belsky, Retsinas and Duda also make a unique contribution by examining how the returns to homeownership are affected by higher mortgage costs. They examine two scenarios: one where owners face interest rates that are 2 percentage points higher than prime rates and another where they are 5 percentage points higher. Under the first scenario, the likelihood that owning would be preferred to renting is decreased by moderate amounts (between 6 and 17 percentage points), while under the later scenario owning is rarely a better financial choice than renting. In short, they find that higher interest rates do reduce the financial appeal of homeownership, although the impact is most pronounced at extremely high levels. Lastly, and in some ways most critically, the finding that renting offers the potential for higher returns than owners depends in large part on renters taking steps to invest the annual savings in housing costs compared to renting. Building on Beracha and Johnson (2012), Beracha, Skiba, and 19 Johnson (2012) examine how variations in key assumptions regarding trends in prices, rents, interest rates, downpayment shares, and the returns available from alternative investments affect the buy versus rent financial calculus. They find that modifying most factors in isolation have only a moderate effect on whether renting is favored over owning. However, when they drop the assumption that renters actual invest any annual savings in housing costs on top of the initial downpayment they find that renting rarely results in higher wealth than owning. Thus, they find that the forced savings aspect of homeownership is of fundamental importance in determining whether owning will lead to greater wealth. This finding is echoed in the results of Boehm and Schlottmann (2004) who employ a somewhat unique approach to simulating the impact of homeownership on wealth accumulation. This study uses the Panel Study of Income Dynamics (PSID) to model the probability of moving in and out of homeownership on an annual basis over the period from 1984 through 1992. These same data are also used to estimate the house value that a household would opt for if a home were purchased in a given year. The estimated house value is then inflated based on house price trends in the census tract where the household resided to yield each household's expected gain in wealth from homeownership. This analysis finds that while minorities and low-income households do accrue wealth from homeownership, the amounts are much less than for higher income whites both because they own for fewer years and because they buy lower valued homes. But importantly, while the expected wealth accumulation among these households is less than that earned by higher income whites it is still positive. The authors also use the PSID to document that these same low-income and minority households essentially had no growth. in non-housing wealth over the same period. So in that regard the estimates of potential wealth created through homeownership were all the more important. Evidence from Panel Surveys about Wealth Accumulation through Homeownership As the findings from Beracha and Johnson (2012) and Boehm and Schlottmann (2004) suggest, the theoretical advantages of renting may not be realized if in practice renters do not take advantage of the opportunities afforded to them for saving and investing derived from the lower cost of renting. In contrast, studies making use of panel surveys that track households over time provide insights into the wealth accumulation associated with actual choices about renting and owning. These studies universally find that owning a home is associated with higher levels of wealth accumulation even after controlling for a range of household characteristics. While the gains are also consistently smaller in magnitude for lower-income and minority households, these studies also find that in contrast to owners similar renters 20 experience little or no gains in wealth. These findings hold even when steps are taken to account for selection bias in who becomes a homeowner. Although these methods may not fully account for the differences between owners and renters, there remains a strong case that homeowning does make a positive contribution to household balance sheets regardless of income or race/ethnicity. Haurin, Hendershott and Wachter (1996) was among the first studies to use panel survey data to track wealth trajectories associated with homeownership. The primary focus of this study was on the accumulation of wealth in anticipation of becoming an owner rather than how owning a home over time contributes to wealth accumulation, but their findings provide important insights into one way in which homeownership adds to wealth. They use the National Longitudinal Survey of Youth (NLSY) to track young renters age 20 to 28 in 1985 through 1990 and observe both their annual wealth levels and the timing of any transitions into homeownership. They find that household wealth goes up markedly during the transition to homeownership, increasing by 33 percent on average in the year prior to buying a home and then more than doubling in the year they first own. When they examine factors that contribute to this jump in wealth they find that marrying makes a significant contribution along with an increase in hours worked and a slightly higher incidence of inheritance and gifts. Their results suggest that an important mechanism by which homeownership adds to wealth is through the incentive to save in anticipation of buying a home. Even before realizing any returns on the investment in the home itself, the drive to become an owner results in substantially higher wealth than those who remain renters. Adding to this effect Haurin and his colleagues also find that wealth increases more rapidly in the years after becoming a homeowner-by 17 percent on average annually among their sample. Reid (2004) uses panel data from the PSID for the period 1976 through 1994 to examine the financial outcomes of homeownership among low-income households who bought their first home at some point during this period (with low-income defined as those with incomes consistently below 80 percent of area median income before first buying a home). She takes two approaches to examining the returns to homeownership for this group. First, she estimates the change in home values for both low- income and minority homeowners compared to higher-income and white owners. She finds that the rate of increase in home values for these groups was fairly modest, failing to beat the returns that would have been earned on an investment in Treasury bills over the same time. Reid then examines wealth holdings of households by tenure status at the end of her period of observation. She finds that while low-income and minority owners generally built much less wealth than higher-income and white households, the amount of their housing wealth was non-trivial and was many times larger than their other forms of wealth. Like Boehm and Schlottmann, she also finds that those who were renters at the 21 end of the period essentially held no wealth of any kind. Reid, however, does not undertake a multivariate analysis to control for other factors that may account for the differences between owners and renters. Nor does she factor in the impact of failed efforts at homeownership on wealth. But the fact that home equity accounts for such a large share of wealth among low-income and minority households points to the important role that owning a home played in fostering wealth accumulation. Di, Belsky and Liu (2007) was the first study to directly assess the relationship between homeownership and wealth accumulation over time while attempting to account for household characteristics and to include some measure of potential selection bias in who becomes an owner. The study uses the PSID to track households who were renters in 1989 through 2001 to observe transitions into and out of homeownership. The change in household wealth over time is then modeled as a function of starting wealth, a range of household characteristics thought to influence wealth, and, their principal measure of interest, the amount of time spent as an owner. In order to take into account a household's propensity to save, the study uses the PSID from 1984 through 1989 to estimate the share of income that was saved as an indication of savings behavior prior to the period when tenure transitions are observed as a means of controlling for this tendency in assessing differences in savings behavior after buying a home. Their principal finding is a positive and statistically significant association between additional years of homeownership and changes in wealth. The authors include a square term for the number of years owned to take into account anticipated impacts of the timing of moves into homeownership over the period as there was an initial decline in house values during the first years of their panel followed by more robust increases in later years. This square term is negative and significant indicating those who bought earlier in the period had lower cumulative gains in wealth. The largest estimated gains in wealth of $13,000 per year of ownership occurred among those who owned for 8 years. But for those who owned for the maximum possible period of 12 years the gains were only $3,333 per year. Prior savings tendency was positively associated with increases in wealth as expected, but was not statistically significant and so did not appear to capture any important difference in household behavior that was not already accounted for by other explanatory variables. Turner and Luea (2009) undertake a very similar analysis using the PSID sample for the period from 1987 to 2001. In contrast to Di, Belsky and Liu who only include initial renters, their study sample includes all households in the sample as of 2001 that were age 65 or younger regardless of whether they were renters at the start of the period. The study pools observations for the sample on household wealth from three points in time: 1994, 1999, and 2001. For each observation they include a count of the number of years the household has owned a home since 1988 as their explanatory variable of 22 interest. The approach used in this study attempts to control for selection bias into homeownership by estimating a random effects model that includes a household specific constant term. Turner and Luea also separate the sample into two income classes to see whether the association between homeownership and wealth growth differs by income. Low- and moderate-income (LMI) households were those who had incomes below 120 percent of area median income in all three periods when wealth was observed. The results indicate that each year of homeownership is associated with nearly $14,000 in additional wealth, perhaps not surprisingly quite similar to the amount found by Di, Belsky and Liu using the same survey over a nearly identical period (although with a somewhat different sample). When controls are included for LMI status, Turner and Luea find that these households have somewhat lower wealth accumulation of between $6,000 and $10,000 per year. But they note that since the average wealth holding of LMI households in 2001 was about $89,000 this annual rate of increase accounts for a fairly sizeable share of total wealth. In an unpublished dissertation, Mamgain (2011) extends the work of Turner and Luea by employing a two-stage model to add stronger controls for selection into homeownership. Like most of the other studies, Mamgain also uses the PSID, but his period of observation is from 1999 through 2007. Despite the different time period examined, when he replicates Turner and Luea his analysis yields similar results regarding the magnitude of the association between homeownership and wealth (although by ending the study period in 2007 it does not include the sharp loss of both housing and financial wealth that followed 2007). When Mamgain adds additional controls to his model to capture the intention to move, the respondent's health status, their ownership of other real estate and an estimate of current LTV he finds a somewhat lower impact of additional years of owning, but the estimate is still significant and positive. Importantly, when he employs his two-stage approach to include both a selection term and an instrumental measure of current tenure his estimate of the impact of each. additional year on owning does not change. He also estimates separate models by income level and finds that there is no difference in the impact of owning across income classes—all are positive and significant. In short, like other studies he does not find a significant impact of selection bias on his findings and he also finds that low-income owners are also likely to benefit from owning homes. 3 3 He does differ from previous studies in how he estimates the contribution of owning to wealth gains, by focusing on impacts at much lower household wealth levels. He finds that assuming wealth of about $2,500 for the lowest income group (at or below 150 percent of the poverty level) owning a home only adds a few hundred dollars a year to the household's bottom line. But with total wealth set a level well below the median among owners in this income class this result seems implausible. 23 None of the studies estimating statistical models to assess the contribution of homeownership to wealth accumulation analyzed whether there were differences in this experience by race and ethnicity. As discussed above, there are significant racial and ethnic differences in residential location, size of home, and characteristics of financing used, all of which could contribute to differences in wealth outcomes. Shapiro, Meschede, and Osoro (2013) use the PSID from 1984 through 2009 specifically to examine the factors associated with more rapid growth in wealth among whites over this period compared to blacks. Tracking the same set of households over this period they find that gains in median wealth among whites exceeded those among blacks by $152,000. Based on the results of a multivariate analysis they found that the single largest driver of this divergence in wealth was the additional time whites spend as homeowners, which they estimate accounted for 27 percent of the additional white gains. The next most significant factors were differences in income (20 percent), unemployment spells (9 percent), lower shares with a college education (5 percent), and differences in inheritance and financial support from family (5 percent). They also find that years of homeownership exerted a stronger influence on gains in wealth for blacks than it did for whites. While the authors do not attempt to control for any selection bias to control for who becomes a homeowner, none of the previous studies that have taken these steps have found these controls to change their findings. Conclusions Drawn from the Previous Literature Studies presenting simulations of the financial returns to renting and owning make a convincing case that in many markets over many periods of time and under a variety of assumptions renting ought to support greater wealth accumulation than owning. However, as virtually all of the panel studies document, in practice owning has consistently been found to be associated with greater increases in wealth even after controlling for differences in household income, education, marital status, starting wealth, inheritances, and other factors. Importantly, these same studies also consistently find that owning has a positive effect on wealth accumulation among both lower-income households and minorities, although the gains are smaller than for higher-income households and whites generally. Housing wealth among lower-income and minority households also often accounts a substantial share of total wealth for these groups. On the other hand, renters in these same demographic groups are consistently found to accrue little to no wealth over time. How can we reconcile the findings from simulation studies that renting should often be more financially advantageous than owning with the findings from the analysis of panel surveys that unambiguously find owning to be more favorable? One explanation may be that behavioral issues play 24 a key role. Efforts to save for a downpayment lead to a large jump in wealth that is then further supported by at least modest appreciation and some pay down of principal over time. Renters may have the opportunity to accrue savings and invest them in higher yielding opportunities but lack strong incentives and effective mechanisms for carrying through on this opportunity. There is also likely some degree of selection bias at work in who becomes a homeowner. While studies do control for income, education, marital status and other factors that would contribute in differences in the ability to save, there are likely differences in motivation and personal attributes that are related to both savings practices and whether someone becomes an owner. While controls included in studies to capture this effect have not diluted the association between homeownership and increases in wealth, this may simply reflect the challenge of capturing these difficult to measure factors. Studies using panel surveys may also make the benefits of homeownership appear more assured than they actually are by not fully capturing the impact of failed attempts at owning on changes in wealth. Studies to date have focused on measuring homeownership as the number of years spent as a homeowner, which does not distinguish between short sustained spells of owning from similar periods of owning that end in foreclosure or other financial distress. So while homeownership on average may increase wealth, it is undoubtedly the case that for some share of households owning a home had a negative impact on their balance sheet. Finally, the studies reviewed here may also not fully reflect changes that have occurred over time in both market conditions and household behavior. Most of the studies cited reflect experiences as owners during the 1980s and 1990s and so do not capture the market dynamics that began in the late 1990s but came to full bloom during the boom years of the 2000s, including the much greater availability of and appetite for high loan-to-value loans, higher cost loans, sharp swings in house prices, and much higher risks of default even before the national foreclosure crisis began. The next section turns to an analysis of data from the 2000s to examine whether findings about homeownership's positive association with wealth accumulation held over this period, particularly for low-income and minority households who were most likely to have used high cost mortgage products. Experience with Homeownership and Wealth Accumulation through the Boom and Bust Given the substantial changes in the availability, cost and terms of mortgage financing that began in the 1990s and accelerated through the mid-2000s and the accompanying boom and bust in home prices, there is good reason to believe that the experience of homeowners in accumulating wealth over the last decade has been substantially different from what is documented in much of the existing 25 literature for earlier periods. In this section of the paper we present information on wealth accumulation through homeownership during the housing market boom and bust of the 2000s. In the first section, we present findings from the tri-annual Survey of Consumer Finance (SCF) to present a high level picture of the contribution of homeownership to household balance sheets over time. The SCF also provides insights into how a greater tendency both to use high loan-to-value (LTV) loans to purchase homes and to take cash out through refinancing may have reduced wealth associated with homeownership. While the SCF does document the substantial decline in housing wealth following the bust, it also shows that, despite these losses, average homeownership wealth is generally higher than it was in the mid-1990s and continues to represent a substantial portion of household wealth for minorities and lower-income households. The SCF also shows that while the degree of leverage in the housing market showed a marked increase in the years following the Tax Reform Act of 1986, the distribution of LTVs did not change a great deal between the mid 1990s and the housing boom years. However, the crash in housing prices did push LTVs to historic highs. We then turn to an analysis of the PSID for the period from 1999 to 2009 to examine how homeownership spells contributed to trends in household wealth over this period. While house prices grew substantially for much of this period, it also captures most of the decline in prices as well. Whereas previous studies have focused solely on how each additional year of homeownership contributes to household wealth, we are also interested in assessing how failed attempts at homeownership affect wealth to assess the downside risks of owning as well. We find that on average homeownership's contribution to household wealth over this period was remarkably similar to that found in earlier periods. The results also confirm previous findings that while lower-income households and minorities realized lower wealth gains from owning, on average these gains were positive and significant. The results also show that a failure to sustain homeownership is associated with a substantial loss of wealth for established owners, although those who made a failed transition from owning to renting are no worse off financially than those who remained renters over the whole period. Thus, despite the many ways in which market conditions over this period might have been expected to undermine homeownership's wealth building potential, our analysis of the PSID finds that owning maintained a strong association with improvements in wealth over the decade from 1999 to 2009. Long-Run Trends in Housing Wealth and Mortgage Debt The sharp rise in home prices in many parts of the country is reflected in the substantial increase in average real housing equity among homeowners, roughly doubling (a gain of 96 percent) between 26 1995 and 2007 among all homeowners (Table 1). The gains were nearly as large among African- Americans (88 percent) and even larger among Hispanics (123 percent), although generally lower among households in the bottom two income quartiles where home equity increased by only 56 and 42 percent, respectively. The loss in housing equity between 2007 and 2010 was substantial, erasing 26 percent of home equity on average for all homeowners and taking back much of the gains made since 2001 for most groups. Mirroring their larger gains during the boom, Hispanics suffered the greatest loss of housing wealth, dropping by nearly half. Across income groups the declines were more moderate among those in the bottom half of the income distribution. But despite these substantial losses, average real home equity in 2010 was still higher on average than in 1995 for all of the groups shown, and in many cases considerably higher. Whites and those in the highest income quartile had the largest gains, with average home equity up by 51 percent and 78 percent respectively. African-Americans and the lowest income quartile also maintained substantial gains of 39 percent and 35 percent, respectively. Hispanics and those in the middle income quartiles made the least progress, with average home equity up by only 12 to 18 percent. Throughout this period the share of net wealth accounted for by home equity among all homeowners fluctuated between 22 and 29 percent, with much of the movement due to changes in non-housing net wealth. Between 1989 and 1998 home equity's share of average wealth fell from 29 to 22 percent as the stock market boomed while home values languished. Between 1998 and 2007 home equity's share of net wealth rose to 25 percent as the stock market absorbed the dot com bust while housing prices soared. Between 2007 and 2010 losses in housing wealth outpaced losses in other financial assets so housing's share of wealth fell back to 22 percent. Thus, despite the significant growth in housing equity in the first half of the 2000s it never came to account for an outsized portion of household net wealth among all homeowners.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

What did researchers find to be the cause of the anti-PD-1 therapy side effects? How did testing mice help in finding the cause? Will these findings help prevent the side effects for cancer patients?

Treatments that enhance the defenses the body already has in place have greatly advanced the fight against cancer. Such a boost is the mechanism underlying an established therapy used for solid cancers, such as melanomas and small-cell lung cancers, and trials are underway for other cancer types. The treatment blocks a protein on immune cells that can lead to cell death, which keeps the immune system in a hyperalert state that makes it better at destroying cancer cells. However, oncologists such as Robert Zeiser at the University of Freiburg in Germany began to see that some patients on this type of cancer immunotherapy experienced neurological side effects such as memory loss, which in a few cases were serious enough to lead to encephalitis or coma. In a recent study in Science Translational Medicine, Zeiser and his postdoctoral researcher Janaki Manoja Vinnakota, along with their colleagues, untangled the reasons why these side effects occur. The protein targeted by this cancer immunotherapy is called PD-1, short for programmed cell death protein-1. The therapy uses an antibody to block this protein’s receptor on T cells. Cancer cells produce markers that turn off immune cells and fool them into seeing the cancer as normal cells. The therapy keeps immune cells active so they don’t recognize these repressive markers and will kill the cancer cells. But keeping the immune system in this hyperactivated state can have negative consequences, because another type of immune cell that resides in the nervous system, called microglia, also have the same receptor. These cells have close interactions with neurons, and help control many brain activities. “Once microglia are active, they also meddle with the normal cognitive processes, which might cause neurotoxicity,” Vinnakota explains. J. M. Vinnakota, et al., 2024, Science Translational Medicine 16:eadj9672 (all 4 images) To see if microglia could be behind the neurological side effects, the team first treated a cell culture of microglia with two different clinically approved anti-PD-1 antibodies. They found an increased level of a marker associated with microglia activity. They next treated healthy mice with the anti-PD-1 therapy. Tissue samples from these mice likewise showed that microglia were activated after the therapy. “Microglia, under normal conditions, are highly branched; they tend to look around for any potential threat,” Vinnakota explains. “If there is one, they retract their processes and attain an amoeboid phenotype.” When the team then tested mice that had a knocked-out immune system, they didn’t see as much activity. One curiosity the researchers had about their findings was that the blood–brain barrier should keep the anti-PD-1 therapy out of the nervous system. But Vinnakota and her colleagues found that the therapy actually causes inflammatory damage to the barrier that allows it to pass through. The team next treated mice with tumors and found that they showed cognitive deficits similar to those seen in human patients. The mice did not favor new objects over ones that they had already been extensively exposed to, indicating that they did not have memory of objects that should have been familiar. The markers produced when the microglia are activated seem to cause the cognitive damage. These markers include a type of enzyme called a tyrosine kinase that acts as a sort of protein switch—in this case, one called Syk. Kinases are important for the function of the immune system, but they also promote inflammation. “Increased levels of Syk activation are somehow damaging the neurons in the vicinity, which is why we see cognitive deficits in the treated mice,” Vinnakota said. The good news, however, is that there are already commercially available inhibitors that work on Syk. When the team treated the cognitively impaired mice with these inhibitors, they were able to reverse the decline. Although the studies so far have been limited to mice, Vinnakota thinks that, following further research, there could one day be the option of blocking Syk in patients receiving anti-PD-1 therapy who start to show indications of cognitive decline. “The people who get cognitive decline are suffering a lot, so they have to stop this anti-PD-1 therapy, and that increases the relapse of the tumor, and then they have to look for some other treatment options,” she says. “It’s really bad for the ones who are suffering.” Optimally, Vinnakota hopes, researchers will develop early-diagnostic tools that can spot patients who are likely to have side effects from anti-PD-1 therapy, so they can be preemptively treated with blockers for Syk. “That would be really helpful to treat them better,” she says, “so that we can still have the anti-PD-1 therapy ongoing, because it is an effective therapy for many of the patients.”

[question] What did researchers find to be the cause of the anti-PD-1 therapy side effects? How did testing mice help in finding the cause? Will these findings help prevent the side effects for cancer patients? ===================== [text] Treatments that enhance the defenses the body already has in place have greatly advanced the fight against cancer. Such a boost is the mechanism underlying an established therapy used for solid cancers, such as melanomas and small-cell lung cancers, and trials are underway for other cancer types. The treatment blocks a protein on immune cells that can lead to cell death, which keeps the immune system in a hyperalert state that makes it better at destroying cancer cells. However, oncologists such as Robert Zeiser at the University of Freiburg in Germany began to see that some patients on this type of cancer immunotherapy experienced neurological side effects such as memory loss, which in a few cases were serious enough to lead to encephalitis or coma. In a recent study in Science Translational Medicine, Zeiser and his postdoctoral researcher Janaki Manoja Vinnakota, along with their colleagues, untangled the reasons why these side effects occur. The protein targeted by this cancer immunotherapy is called PD-1, short for programmed cell death protein-1. The therapy uses an antibody to block this protein’s receptor on T cells. Cancer cells produce markers that turn off immune cells and fool them into seeing the cancer as normal cells. The therapy keeps immune cells active so they don’t recognize these repressive markers and will kill the cancer cells. But keeping the immune system in this hyperactivated state can have negative consequences, because another type of immune cell that resides in the nervous system, called microglia, also have the same receptor. These cells have close interactions with neurons, and help control many brain activities. “Once microglia are active, they also meddle with the normal cognitive processes, which might cause neurotoxicity,” Vinnakota explains. J. M. Vinnakota, et al., 2024, Science Translational Medicine 16:eadj9672 (all 4 images) To see if microglia could be behind the neurological side effects, the team first treated a cell culture of microglia with two different clinically approved anti-PD-1 antibodies. They found an increased level of a marker associated with microglia activity. They next treated healthy mice with the anti-PD-1 therapy. Tissue samples from these mice likewise showed that microglia were activated after the therapy. “Microglia, under normal conditions, are highly branched; they tend to look around for any potential threat,” Vinnakota explains. “If there is one, they retract their processes and attain an amoeboid phenotype.” When the team then tested mice that had a knocked-out immune system, they didn’t see as much activity. One curiosity the researchers had about their findings was that the blood–brain barrier should keep the anti-PD-1 therapy out of the nervous system. But Vinnakota and her colleagues found that the therapy actually causes inflammatory damage to the barrier that allows it to pass through. The team next treated mice with tumors and found that they showed cognitive deficits similar to those seen in human patients. The mice did not favor new objects over ones that they had already been extensively exposed to, indicating that they did not have memory of objects that should have been familiar. The markers produced when the microglia are activated seem to cause the cognitive damage. These markers include a type of enzyme called a tyrosine kinase that acts as a sort of protein switch—in this case, one called Syk. Kinases are important for the function of the immune system, but they also promote inflammation. “Increased levels of Syk activation are somehow damaging the neurons in the vicinity, which is why we see cognitive deficits in the treated mice,” Vinnakota said. The good news, however, is that there are already commercially available inhibitors that work on Syk. When the team treated the cognitively impaired mice with these inhibitors, they were able to reverse the decline. Although the studies so far have been limited to mice, Vinnakota thinks that, following further research, there could one day be the option of blocking Syk in patients receiving anti-PD-1 therapy who start to show indications of cognitive decline. “The people who get cognitive decline are suffering a lot, so they have to stop this anti-PD-1 therapy, and that increases the relapse of the tumor, and then they have to look for some other treatment options,” she says. “It’s really bad for the ones who are suffering.” Optimally, Vinnakota hopes, researchers will develop early-diagnostic tools that can spot patients who are likely to have side effects from anti-PD-1 therapy, so they can be preemptively treated with blockers for Syk. “That would be really helpful to treat them better,” she says, “so that we can still have the anti-PD-1 therapy ongoing, because it is an effective therapy for many of the patients.” https://www.americanscientist.org/article/treating-the-side-effects ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

For this question, make sure you only use the information I give to you. Focus on terms the average person would understand.

Identify the difference between dividends and earnings.

1. Amortization: Refers to the process of gradually paying off a debt or loan over a specific period of time through regular, scheduled payments. These payments typically consist of both principal and interest. 2. Backlog: A buildup of work that has not been completed or processed within a specific period. When a company receives an order or new contract for a product, undelivered products to fulfill that contract become part of the company’s backlog. 3. Balance Sheet: Financial statement that provides a snapshot of a company's financial position at a specific point in time. It is one of the financial statements used by businesses, investors, creditors, and analysts to assess the company's financial health and performance. The balance sheet follows the accounting equation that assets must equal liabilities plus equity. 4. Bid & Proposal Costs: Refers to the costs incurred in preparing, submitting, and supporting bids and proposals (whether or not solicited) on potential contracts (Government or not). These typically indirect costs are allowable to the extent they are allocable, reasonable, and not otherwise unallowable. 5. Booking (e.g., Orders): Refers to the value of new contracts, modifications, task orders, or options signed in an accounting period. 6. Cash Flow: Refers to the inflows (coming in) and outflows (going out) of cash of a company. 7. Cash Flow Statement: Financial statement that provides an overview of the cash generated and used by a business during a specific period of time. It is one of the key financial statements used by businesses, investors, and analysts to assess the financial health and liquidity of a company. The cash flow statement is divided into three main sections: 1) Operating Activities: Reports the cash generated or used in the core operating activities of the business. 2) Investing Activities: Details cash transactions related to the purchase and sale of long-term assets and investments. 3) Financing Activities: Reflects cash transactions related to the company's financing activities. It includes activities such as issuing or repurchasing stock, borrowing, or repaying debt, and paying dividends. 8. Common Size Financial Analysis: Method of evaluating and comparing financial statements by expressing each line item as a percentage of a base item (e.g., revenue for income statement or assets for balance sheet). The purpose of common size analysis is to provide insights into the relative proportions of different components within a financial statement, allowing for better comparison of companies of different sizes or of the same company over different periods. 9. Cost of Sales or Cost of Goods Sold: Represents the costs associated with producing or purchasing the goods that a company sells during a specific period. It is a crucial metric for businesses, as it is subtracted from the total revenue to calculate the gross profit 10. Current Assets: Any balance sheet accounts owned by a company that can be converted to cash through liquidation, sales, or use within one year. Examples may include cash (or equivalent), accounts receivable, prepaid expenses, raw materials, inventory (work-in-process or finished goods), short-term investments, etc. 11. Current Liabilities: Any balance sheet accounts that are obligations by a company that are due to be paid within one year. Examples may include accounts payable, payroll, taxes, utilities, rental fees, shortterm notes payable, etc. 12. Debt Ratio: A financial leverage metric based on a company’s total debt to total assets from the Balance Sheet. Debt Ratio = Total Liabilities / Total Assets (less Depreciation). 13. Depreciation: Refers to the decrease in the value of an asset over time due to various factors such as wear and tear, obsolescence, or other forms of reduction in its usefulness. It is a common accounting concept used to allocate the cost of a tangible asset (like machinery, vehicles, buildings, etc.) over its useful life. Often an expense item on the Income Statement. 14. Discount rate: Refers to the interest rate used to determine the present value of future cash flows. The concept is fundamental in the field of discounted cash flow (DCF) analysis, which is a method used to value an investment or project by discounting its expected future cash flows back to their present value. 15. Dividends: Payments made by a company to its shareholders, typically in the form of cash or additional shares of stock. They represent a portion of the company's profits that is distributed to its owners. 16. Earnings: Typically refers to the profits or net income of a business during a specific period. Earnings represent the financial performance of a company and are a key indicator of its profitability, 17. Earnings per Share (EPS, ratio): Financial profitability metric that represents the portion of a company's profit allocated to each outstanding share of common stock. It is a widely used indicator of a company's profitability and is often considered a key measure of financial performance. Calculated as net income minus preferred dividends divided by average number of common shares. 18. Earnings Before Interest and Taxes (EBIT): A measure of a company's operating performance and profitability before deducting interest expenses and taxes. EBIT is often used to analyze a company's core operating profitability without the influence of financial structure or tax considerations. EBIT provides a metric that allows for comparisons of the operating performance of different companies, as it excludes the impact of financing and taxation. (See operating income) 19. Free Cash Flow (FCF): Metric that represents the cash generated by a company's operations that is available for distribution to creditors and investors (both equity and debt holders) after all operating expenses, capital expenditures, and taxes have been deducted. It means the company has the ability to distribute cash to investors, pay down debt, or reinvest in the business. FCF=Operating Cash Flow - Capital Expenditures 20. Gross Profit: Metric represents the difference between revenue and the cost of sales during a specific period. While gross profit provides useful insights, it doesn't consider other operating expenses or nonoperating income, so it's often used in conjunction with other financial metrics to get a more comprehensive view of a company's overall financial health. Gross Profit = Sales – Cost of Sales. 21. Gross Profit Margin: Financial metric that measures the percentage of revenue that exceeds the cost of sales. It is a key indicator of a company's profitability and efficiency in managing its production and supply chain costs. 22. Income (or Profit): This is a metric that reflects the Income Statement’s bottom line or the amount of money a business has left over after all expenses. Gross income is the amount earned before expenses. (also known as gross profit). See Net Income. 23. Income Statement: Financial statement used to summarize company revenue, costs, and expenses over a specific period, usually a fiscal quarter or year. The main purpose of an income statement is to provide a snapshot of a company's financial performance during a given time frame. 24. Internal Rate of Return (IRR): Metric in financial analysis to estimate and compare the profitability of potential investments. Represents the expected compound annual rate of return that will be earned on a project. Typically, investments with higher IRRs are preferred as companies decide which projects to invest in.

For this question, make sure you only use the information I give to you. Focus on terms the average person would understand. 1. Amortization: Refers to the process of gradually paying off a debt or loan over a specific period of time through regular, scheduled payments. These payments typically consist of both principal and interest. 2. Backlog: A buildup of work that has not been completed or processed within a specific period. When a company receives an order or new contract for a product, undelivered products to fulfill that contract become part of the company’s backlog. 3. Balance Sheet: Financial statement that provides a snapshot of a company's financial position at a specific point in time. It is one of the financial statements used by businesses, investors, creditors, and analysts to assess the company's financial health and performance. The balance sheet follows the accounting equation that assets must equal liabilities plus equity. 4. Bid & Proposal Costs: Refers to the costs incurred in preparing, submitting, and supporting bids and proposals (whether or not solicited) on potential contracts (Government or not). These typically indirect costs are allowable to the extent they are allocable, reasonable, and not otherwise unallowable. 5. Booking (e.g., Orders): Refers to the value of new contracts, modifications, task orders, or options signed in an accounting period. 6. Cash Flow: Refers to the inflows (coming in) and outflows (going out) of cash of a company. 7. Cash Flow Statement: Financial statement that provides an overview of the cash generated and used by a business during a specific period of time. It is one of the key financial statements used by businesses, investors, and analysts to assess the financial health and liquidity of a company. The cash flow statement is divided into three main sections: 1) Operating Activities: Reports the cash generated or used in the core operating activities of the business. 2) Investing Activities: Details cash transactions related to the purchase and sale of long-term assets and investments. 3) Financing Activities: Reflects cash transactions related to the company's financing activities. It includes activities such as issuing or repurchasing stock, borrowing, or repaying debt, and paying dividends. 8. Common Size Financial Analysis: Method of evaluating and comparing financial statements by expressing each line item as a percentage of a base item (e.g., revenue for income statement or assets for balance sheet). The purpose of common size analysis is to provide insights into the relative proportions of different components within a financial statement, allowing for better comparison of companies of different sizes or of the same company over different periods. 9. Cost of Sales or Cost of Goods Sold: Represents the costs associated with producing or purchasing the goods that a company sells during a specific period. It is a crucial metric for businesses, as it is subtracted from the total revenue to calculate the gross profit 10. Current Assets: Any balance sheet accounts owned by a company that can be converted to cash through liquidation, sales, or use within one year. Examples may include cash (or equivalent), accounts receivable, prepaid expenses, raw materials, inventory (work-in-process or finished goods), short-term investments, etc. 11. Current Liabilities: Any balance sheet accounts that are obligations by a company that are due to be paid within one year. Examples may include accounts payable, payroll, taxes, utilities, rental fees, shortterm notes payable, etc. 12. Debt Ratio: A financial leverage metric based on a company’s total debt to total assets from the Balance Sheet. Debt Ratio = Total Liabilities / Total Assets (less Depreciation). 13. Depreciation: Refers to the decrease in the value of an asset over time due to various factors such as wear and tear, obsolescence, or other forms of reduction in its usefulness. It is a common accounting concept used to allocate the cost of a tangible asset (like machinery, vehicles, buildings, etc.) over its useful life. Often an expense item on the Income Statement. 14. Discount rate: Refers to the interest rate used to determine the present value of future cash flows. The concept is fundamental in the field of discounted cash flow (DCF) analysis, which is a method used to value an investment or project by discounting its expected future cash flows back to their present value. 15. Dividends: Payments made by a company to its shareholders, typically in the form of cash or additional shares of stock. They represent a portion of the company's profits that is distributed to its owners. 16. Earnings: Typically refers to the profits or net income of a business during a specific period. Earnings represent the financial performance of a company and are a key indicator of its profitability, 17. Earnings per Share (EPS, ratio): Financial profitability metric that represents the portion of a company's profit allocated to each outstanding share of common stock. It is a widely used indicator of a company's profitability and is often considered a key measure of financial performance. Calculated as net income minus preferred dividends divided by average number of common shares. 18. Earnings Before Interest and Taxes (EBIT): A measure of a company's operating performance and profitability before deducting interest expenses and taxes. EBIT is often used to analyze a company's core operating profitability without the influence of financial structure or tax considerations. EBIT provides a metric that allows for comparisons of the operating performance of different companies, as it excludes the impact of financing and taxation. (See operating income) 19. Free Cash Flow (FCF): Metric that represents the cash generated by a company's operations that is available for distribution to creditors and investors (both equity and debt holders) after all operating expenses, capital expenditures, and taxes have been deducted. It means the company has the ability to distribute cash to investors, pay down debt, or reinvest in the business. FCF=Operating Cash Flow - Capital Expenditures 20. Gross Profit: Metric represents the difference between revenue and the cost of sales during a specific period. While gross profit provides useful insights, it doesn't consider other operating expenses or nonoperating income, so it's often used in conjunction with other financial metrics to get a more comprehensive view of a company's overall financial health. Gross Profit = Sales – Cost of Sales. 21. Gross Profit Margin: Financial metric that measures the percentage of revenue that exceeds the cost of sales. It is a key indicator of a company's profitability and efficiency in managing its production and supply chain costs. 22. Income (or Profit): This is a metric that reflects the Income Statement’s bottom line or the amount of money a business has left over after all expenses. Gross income is the amount earned before expenses. (also known as gross profit). See Net Income. 23. Income Statement: Financial statement used to summarize company revenue, costs, and expenses over a specific period, usually a fiscal quarter or year. The main purpose of an income statement is to provide a snapshot of a company's financial performance during a given time frame. 24. Internal Rate of Return (IRR): Metric in financial analysis to estimate and compare the profitability of potential investments. Represents the expected compound annual rate of return that will be earned on a project. Typically, investments with higher IRRs are preferred as companies decide which projects to invest in. Identify the difference between dividends and earnings.

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Should internet providers be protected from all liability for information posted on their websites by third parties? Describe the pros and cons of keeping such protection in place, in a bullet list, and give a final judgment of which side is more persuasive.

DEPARTMENT OF JUSTICE’S REVIEW OF SECTION 230 OF THE COMMUNICATIONS DECENCY ACT OF 1996 Office of the Attorney General As part of the President's Executive Order on Preventing Online Censorship, and as a result of the Department's long standing review of Section 230, the Department has put together the following legislative package to reform Section 230. The proposal focuses on the two big areas of concern that were highlighted by victims, businesses, and other stakeholders in the conversations and meetings the Department held to discuss the issue. First, it addresses unclear and inconsistent moderation practices that limit speech and go beyond the text of the existing statute. Second, it addresses the proliferation of illicit and harmful content online that leaves victims without any civil recourse. Taken together, the Department's legislative package provides a clear path forward on modernizing Section 230 to encourage a safer and more open internet. Cover Letter: A letter to Congress explaining the need for Section 230 reform and how the Department proposes to reform it. Redline: A copy of the existing law with the Department's proposed changes in redline. Section by Section: An accompanying document to the redline that provides a detailed description and purpose for each edit to the existing statute. Read More As part of its broader review of market-leading online platforms, the U.S. Department of Justice analyzed Section 230 of the Communications Decency Act of 1996, which provides immunity to online platforms from civil liability based on third-party content and for the removal of content in certain circumstances. Congress originally enacted the statute to nurture a nascent industry while also incentivizing online platforms to remove content harmful to children. The combination of significant technological changes since 1996 and the expansive interpretation that courts have given Section 230, however, has left online platforms both immune for a wide array of illicit activity on their services and free to moderate content with little transparency or accountability. The Department of Justice has concluded that the time is ripe to realign the scope of Section 230 with the realities of the modern internet. Reform is important now more than ever. Every year, more citizens—including young children—are relying on the internet for everyday activities, while online criminal activity continues to grow. We must ensure that the internet is both an open and safe space for our society. Based on engagement with experts, industry, thought-leaders, lawmakers, and the public, the Department has identified a set of concrete reform proposals to provide stronger incentives for online platforms to address illicit material on their services, while continuing to foster innovation and free speech. Read the Department’s Key Takeaways. The Department's review of Section 230 arose in the context of our broader review of market-leading online platforms and their practices, announced in July 2019. While competition has been a core part of the Department’s review, we also recognize that not all concerns raised about online platforms (including internet-based businesses and social media platforms) fall squarely within the U.S. antitrust laws. Our review has therefore looked broadly at other legal and policy frameworks applicable to online platforms. One key part of that legal landscape is Section 230, which provides immunity to online platforms from civil liability based on third-party content as well as immunity for removal of content in certain circumstances. Drafted in the early years of internet commerce, Section 230 was enacted in response to a problem that incipient online platforms were facing. In the years leading up to Section 230, courts had held that an online platform that passively hosted third-party content was not liable as a publisher if any of that content was defamatory, but that a platform would be liable as a publisher for all its third-party content if it exercised discretion to remove any third-party material. Platforms therefore faced a dilemma: They could try to moderate third-party content but risk being held liable for any and all content posted by third parties, or choose not to moderate content to avoid liability but risk having their services overrun with obscene or unlawful content. Congress enacted Section 230 in part to resolve this quandary by providing immunity to online platforms both for third-party content on their services or for removal of certain categories of content. The statute was meant to nurture emerging internet businesses while also incentivizing them to regulate harmful online content. The internet has changed dramatically in the 25 years since Section 230’s enactment in ways that no one, including the drafters of Section 230, could have predicted. Several online platforms have transformed into some of the nation’s largest and most valuable companies, and today’s online services bear little resemblance to the rudimentary offerings in 1996. Platforms no longer function as simple forums for posting third-party content, but instead use sophisticated algorithms to promote content and connect users. Platforms also now offer an ever-expanding array of services, playing an increasingly essential role in how Americans communicate, access media, engage in commerce, and generally carry on their everyday lives. These developments have brought enormous benefits to society. But they have also had downsides. Criminals and other wrongdoers are increasingly turning to online platforms to engage in a host of unlawful activities, including child sexual exploitation, selling illicit drugs, cyberstalking, human trafficking, and terrorism. At the same time, courts have interpreted the scope of Section 230 immunity very broadly, diverging from its original purpose. This expansive statutory interpretation, combined with technological developments, has reduced the incentives of online platforms to address illicit activity on their services and, at the same time, left them free to moderate lawful content without transparency or accountability. The time has therefore come to realign the scope of Section 230 with the realities of the modern internet so that it continues to foster innovation and free speech but also provides stronger incentives for online platforms to address illicit material on their services. Much of the modern debate over Section 230 has been at opposite ends of the spectrum. Many have called for an outright repeal of the statute in light of the changed technological landscape and growing online harms. Others, meanwhile, have insisted that Section 230 be left alone and claimed that any reform will crumble the tech industry. Based on our analysis and external engagement, the Department believes there is productive middle ground and has identified a set of measured, yet concrete proposals that address many of the concerns raised about Section 230. A reassessment of America’s laws governing the internet could not be timelier. Citizens are relying on the internet more than ever for commerce, entertainment, education, employment, and public discourse. School closings in light of the COVID-19 pandemic mean that children are spending more time online, at times unsupervised, while more and more criminal activity is moving online. All of these factors make it imperative that we maintain the internet as an open and safe space.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== Should internet providers be protected from all liability for information posted on their websites by third parties? Describe the pros and cons of keeping such protection in place, in a bullet list, and give a final judgment of which side is more persuasive. {passage 0} ========== DEPARTMENT OF JUSTICE’S REVIEW OF SECTION 230 OF THE COMMUNICATIONS DECENCY ACT OF 1996 Office of the Attorney General As part of the President's Executive Order on Preventing Online Censorship, and as a result of the Department's long standing review of Section 230, the Department has put together the following legislative package to reform Section 230. The proposal focuses on the two big areas of concern that were highlighted by victims, businesses, and other stakeholders in the conversations and meetings the Department held to discuss the issue. First, it addresses unclear and inconsistent moderation practices that limit speech and go beyond the text of the existing statute. Second, it addresses the proliferation of illicit and harmful content online that leaves victims without any civil recourse. Taken together, the Department's legislative package provides a clear path forward on modernizing Section 230 to encourage a safer and more open internet. Cover Letter: A letter to Congress explaining the need for Section 230 reform and how the Department proposes to reform it. Redline: A copy of the existing law with the Department's proposed changes in redline. Section by Section: An accompanying document to the redline that provides a detailed description and purpose for each edit to the existing statute. Read More As part of its broader review of market-leading online platforms, the U.S. Department of Justice analyzed Section 230 of the Communications Decency Act of 1996, which provides immunity to online platforms from civil liability based on third-party content and for the removal of content in certain circumstances. Congress originally enacted the statute to nurture a nascent industry while also incentivizing online platforms to remove content harmful to children. The combination of significant technological changes since 1996 and the expansive interpretation that courts have given Section 230, however, has left online platforms both immune for a wide array of illicit activity on their services and free to moderate content with little transparency or accountability. The Department of Justice has concluded that the time is ripe to realign the scope of Section 230 with the realities of the modern internet. Reform is important now more than ever. Every year, more citizens—including young children—are relying on the internet for everyday activities, while online criminal activity continues to grow. We must ensure that the internet is both an open and safe space for our society. Based on engagement with experts, industry, thought-leaders, lawmakers, and the public, the Department has identified a set of concrete reform proposals to provide stronger incentives for online platforms to address illicit material on their services, while continuing to foster innovation and free speech. Read the Department’s Key Takeaways. The Department's review of Section 230 arose in the context of our broader review of market-leading online platforms and their practices, announced in July 2019. While competition has been a core part of the Department’s review, we also recognize that not all concerns raised about online platforms (including internet-based businesses and social media platforms) fall squarely within the U.S. antitrust laws. Our review has therefore looked broadly at other legal and policy frameworks applicable to online platforms. One key part of that legal landscape is Section 230, which provides immunity to online platforms from civil liability based on third-party content as well as immunity for removal of content in certain circumstances. Drafted in the early years of internet commerce, Section 230 was enacted in response to a problem that incipient online platforms were facing. In the years leading up to Section 230, courts had held that an online platform that passively hosted third-party content was not liable as a publisher if any of that content was defamatory, but that a platform would be liable as a publisher for all its third-party content if it exercised discretion to remove any third-party material. Platforms therefore faced a dilemma: They could try to moderate third-party content but risk being held liable for any and all content posted by third parties, or choose not to moderate content to avoid liability but risk having their services overrun with obscene or unlawful content. Congress enacted Section 230 in part to resolve this quandary by providing immunity to online platforms both for third-party content on their services or for removal of certain categories of content. The statute was meant to nurture emerging internet businesses while also incentivizing them to regulate harmful online content. The internet has changed dramatically in the 25 years since Section 230’s enactment in ways that no one, including the drafters of Section 230, could have predicted. Several online platforms have transformed into some of the nation’s largest and most valuable companies, and today’s online services bear little resemblance to the rudimentary offerings in 1996. Platforms no longer function as simple forums for posting third-party content, but instead use sophisticated algorithms to promote content and connect users. Platforms also now offer an ever-expanding array of services, playing an increasingly essential role in how Americans communicate, access media, engage in commerce, and generally carry on their everyday lives. These developments have brought enormous benefits to society. But they have also had downsides. Criminals and other wrongdoers are increasingly turning to online platforms to engage in a host of unlawful activities, including child sexual exploitation, selling illicit drugs, cyberstalking, human trafficking, and terrorism. At the same time, courts have interpreted the scope of Section 230 immunity very broadly, diverging from its original purpose. This expansive statutory interpretation, combined with technological developments, has reduced the incentives of online platforms to address illicit activity on their services and, at the same time, left them free to moderate lawful content without transparency or accountability. The time has therefore come to realign the scope of Section 230 with the realities of the modern internet so that it continues to foster innovation and free speech but also provides stronger incentives for online platforms to address illicit material on their services. Much of the modern debate over Section 230 has been at opposite ends of the spectrum. Many have called for an outright repeal of the statute in light of the changed technological landscape and growing online harms. Others, meanwhile, have insisted that Section 230 be left alone and claimed that any reform will crumble the tech industry. Based on our analysis and external engagement, the Department believes there is productive middle ground and has identified a set of measured, yet concrete proposals that address many of the concerns raised about Section 230. A reassessment of America’s laws governing the internet could not be timelier. Citizens are relying on the internet more than ever for commerce, entertainment, education, employment, and public discourse. School closings in light of the COVID-19 pandemic mean that children are spending more time online, at times unsupervised, while more and more criminal activity is moving online. All of these factors make it imperative that we maintain the internet as an open and safe space. https://www.justice.gov/archives/ag/department-justice-s-review-section-230-communications-decency-act-1996

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

I find the nasal swabs when I get a COVID-19 test really uncomfortable. I don't know what alternatives I have. Are there other ways to collect a sample?

Laboratory results One included studies collected the main specimens from nasopharyngeal and throat of 42 confirmed patients. However, they assessed the possibility of detection of SARS-CoV-2 from saliva specimen in just one confirmed case [17]. The results of this study showed that the viral load in saliva specimen of patient was 5.9 × 106 copies per ml and 3.3 × 106 in pooled nasopharyngeal and throat swab. In another study, 12 patient with laboratory-confirmed SARS-CoV-2 infection (nasopharyngeal or sputum specimens) were included [9]. The researchers reported that the SARS-CoV-2 was detected in saliva specimens of 11 patients (91.7%) in this trial. The median viral load of these 11 patients was 3.3 × 106 copies per ml. It is interesting that among these SARS-CoV-2 positive cases, viral cultures were positive for three patients. Later in another article, this research team published the complementary results of their cohort study. In this paper they reported the results of investigation among 23 COVID-19 patients. The results were in accordance with the previous study and showed that the SARS-CoV-2 was detected in saliva specimens of 87% of included subjects [20]. Based on the results of included studies, three of them were performed among the Chinese participants. One of these studies included 65 cases and the other one recruited 31 confirmed COVID-19 patients [18, 19]. The results of the first project showed that the detection rate of SARS-CoV-2 based on sputum (95.65%) and saliva (88.09%) specimens were significantly higher than throat or nasal swabs (P < 0.001, 20). The authors also reported no significant difference between sputum and saliva samples regarding viral load (P < 0.05). The study from Chen et al. showed that among the 13 patients whose oropharyngeal swab tests were positive, 4 cases were also positive for their saliva specimens [19]. The latest study among the Chinese patients, reported the results based on a total of 1846 respiratory samples (1178 saliva and 668 sputum specimens) from 96 confirmed cases [22]. The authors reported that the SARS-CoV-2 was detected in all 96 patients by testing respiratory samples [22]. The other two studies conducted in Australia and Italy among confirmed COVID-19 patients. These studies reported a detection rate of 84.6 and 100% respectively, based on saliva specimens [21, 24]. One of the included studies in this review is a case-report regarding a confirmed SARS-CoV-2 neonate [23]. In this case, the SARS-CoV-2 was detected in all of the neonate’s clinical specimens, including blood, urine, stool, and saliva along with the upper respiratory tract specimens. Discussion One of the main concerns regarding epidemic prevention and control of any infectious disease is rapid and accurate screening of suspected patients. Apart from the level of sensitivity and specificity of laboratory techniques, selecting the appropriate sites to collect samples is very important. Selection of proper sampling method should be based on the tissue affinity of targeted virus, cost-effectiveness of method and also safety of patients and clinicians [18, 25]. In this study we classified the current evidence regarding the reliability of saliva as a diagnostic specimen in COVID-19 patients. Most of the studies included in this review, reported that there is no statistically significant difference between nasopharyngeal or sputum specimens and saliva samples regarding viral load. These studies suggested saliva as a non-invasive specimen type for the diagnosis and viral load monitoring of SARS-CoV-2 [9, 17, 18, 20,21,22, 24]. Previous studies also reported a high overall agreement between saliva and nasopharyngeal aspirate specimens when tested by an automated multiplex molecular assay approved for point-of-care testing [12, 26, 27]. Based on these studies, the method of collection of saliva and collection device types are critical issues in the way of using saliva as diagnostic specimen. In this regard there are three main types of human saliva (whole saliva, parotid gland and minor gland) and the method of collection of each type varies accordingly [26]. When the aim of sampling is detecting the respiratory viruses with molecular assays, collecting the whole saliva from the suspected patients is useful [26]. In this regard the patients should be instructed to expectorate saliva into a sterile container. The volume of saliva should be ranged between 0.5 and 1 ml. Then 2 ml of viral transport medium (VTM) should be added to the container [11]. The next procedures will be conducted based on instructions of related RT-PCR technique in the microbiology laboratory. The low concordance rate of saliva with nasopharyngeal specimens reported in the research of Chen et al. might be explained by the differences in the method of obtaining the samples [19]. This study reported the detection rate of SARS-CoV-2 in pure saliva fluid secreted from the opening of salivary gland canals. However in other studies patients were asked to cough out saliva from their throat into sterile containers, and hence the saliva samples were mainly sputum from the lower respiratory tract [9, 17, 18]. Thus for increasing the sensitivity of salivary tests in the way of diagnosing the suspected COVID-19 patients, the instructions should clearly explain the correct procedure to the individuals. The use of saliva samples for diagnosis of SARS-CoV-2 has many advantages in clinical practice. First, collecting saliva is a non-invasive procedure and rather than nasal or throat swabs avoids patient discomfort. The second advantage of using saliva as specimen is related to possibility of collecting samples outside the hospitals. This sampling method doesn’t require the intervention of healthcare personnel and the suspected patients can provide it by themselves. Therefore this method can decrease the risk of nosocomial SARS-CoV-2 transmission. Furthermore, because there is not necessary for presence of trained healthcare workers for collecting saliva specimen, the waiting time for suspected patients will be reduced. This is crucial in busy clinical settings where a large number of individuals require screening. The results of viral culture in one of the included studies showed that saliva collected from COVID-19 patients, may contain live viruses which may allow transmission of virus from person to person [9]. These finding reinforce the use of barrier-protection equipment as a control measure, for all healthcare workers in the clinic/hospital settings during the epidemic period of COVID-19. It should be mentioned that this study has several limitations. Firstly, the outbreak and detection of SARS-CoV-2 has begun very recently; therefore the available data in this regard is very scarce. Secondly the included studies of this review didn’t evaluate other factors such as severity of disease or disease progression that may impact on detection rate of the virus. Finally as all of the selected studies only included hospitalized confirmed COVID-19 patients, further studies should be performed in outpatient settings. Conclusions In conclusion, although further research is warranted as the weight of the evidence increases, saliva can be considered as a non-invasive specimen for screening SARS-CoV-2 suspected patients. This method of sampling has proper accuracy and reliability regarding viral load monitoring of SARS-CoV-2 based on RT-PCR technique. Since oropharyngeal samples may cause discomfort to patients, saliva sampling after deep cough, could be recommended as an appropriate alternative.

"================ <TEXT PASSAGE> ======= Laboratory results One included studies collected the main specimens from nasopharyngeal and throat of 42 confirmed patients. However, they assessed the possibility of detection of SARS-CoV-2 from saliva specimen in just one confirmed case [17]. The results of this study showed that the viral load in saliva specimen of patient was 5.9 × 106 copies per ml and 3.3 × 106 in pooled nasopharyngeal and throat swab. In another study, 12 patient with laboratory-confirmed SARS-CoV-2 infection (nasopharyngeal or sputum specimens) were included [9]. The researchers reported that the SARS-CoV-2 was detected in saliva specimens of 11 patients (91.7%) in this trial. The median viral load of these 11 patients was 3.3 × 106 copies per ml. It is interesting that among these SARS-CoV-2 positive cases, viral cultures were positive for three patients. Later in another article, this research team published the complementary results of their cohort study. In this paper they reported the results of investigation among 23 COVID-19 patients. The results were in accordance with the previous study and showed that the SARS-CoV-2 was detected in saliva specimens of 87% of included subjects [20]. Based on the results of included studies, three of them were performed among the Chinese participants. One of these studies included 65 cases and the other one recruited 31 confirmed COVID-19 patients [18, 19]. The results of the first project showed that the detection rate of SARS-CoV-2 based on sputum (95.65%) and saliva (88.09%) specimens were significantly higher than throat or nasal swabs (P < 0.001, 20). The authors also reported no significant difference between sputum and saliva samples regarding viral load (P < 0.05). The study from Chen et al. showed that among the 13 patients whose oropharyngeal swab tests were positive, 4 cases were also positive for their saliva specimens [19]. The latest study among the Chinese patients, reported the results based on a total of 1846 respiratory samples (1178 saliva and 668 sputum specimens) from 96 confirmed cases [22]. The authors reported that the SARS-CoV-2 was detected in all 96 patients by testing respiratory samples [22]. The other two studies conducted in Australia and Italy among confirmed COVID-19 patients. These studies reported a detection rate of 84.6 and 100% respectively, based on saliva specimens [21, 24]. One of the included studies in this review is a case-report regarding a confirmed SARS-CoV-2 neonate [23]. In this case, the SARS-CoV-2 was detected in all of the neonate’s clinical specimens, including blood, urine, stool, and saliva along with the upper respiratory tract specimens. Discussion One of the main concerns regarding epidemic prevention and control of any infectious disease is rapid and accurate screening of suspected patients. Apart from the level of sensitivity and specificity of laboratory techniques, selecting the appropriate sites to collect samples is very important. Selection of proper sampling method should be based on the tissue affinity of targeted virus, cost-effectiveness of method and also safety of patients and clinicians [18, 25]. In this study we classified the current evidence regarding the reliability of saliva as a diagnostic specimen in COVID-19 patients. Most of the studies included in this review, reported that there is no statistically significant difference between nasopharyngeal or sputum specimens and saliva samples regarding viral load. These studies suggested saliva as a non-invasive specimen type for the diagnosis and viral load monitoring of SARS-CoV-2 [9, 17, 18, 20,21,22, 24]. Previous studies also reported a high overall agreement between saliva and nasopharyngeal aspirate specimens when tested by an automated multiplex molecular assay approved for point-of-care testing [12, 26, 27]. Based on these studies, the method of collection of saliva and collection device types are critical issues in the way of using saliva as diagnostic specimen. In this regard there are three main types of human saliva (whole saliva, parotid gland and minor gland) and the method of collection of each type varies accordingly [26]. When the aim of sampling is detecting the respiratory viruses with molecular assays, collecting the whole saliva from the suspected patients is useful [26]. In this regard the patients should be instructed to expectorate saliva into a sterile container. The volume of saliva should be ranged between 0.5 and 1 ml. Then 2 ml of viral transport medium (VTM) should be added to the container [11]. The next procedures will be conducted based on instructions of related RT-PCR technique in the microbiology laboratory. The low concordance rate of saliva with nasopharyngeal specimens reported in the research of Chen et al. might be explained by the differences in the method of obtaining the samples [19]. This study reported the detection rate of SARS-CoV-2 in pure saliva fluid secreted from the opening of salivary gland canals. However in other studies patients were asked to cough out saliva from their throat into sterile containers, and hence the saliva samples were mainly sputum from the lower respiratory tract [9, 17, 18]. Thus for increasing the sensitivity of salivary tests in the way of diagnosing the suspected COVID-19 patients, the instructions should clearly explain the correct procedure to the individuals. The use of saliva samples for diagnosis of SARS-CoV-2 has many advantages in clinical practice. First, collecting saliva is a non-invasive procedure and rather than nasal or throat swabs avoids patient discomfort. The second advantage of using saliva as specimen is related to possibility of collecting samples outside the hospitals. This sampling method doesn’t require the intervention of healthcare personnel and the suspected patients can provide it by themselves. Therefore this method can decrease the risk of nosocomial SARS-CoV-2 transmission. Furthermore, because there is not necessary for presence of trained healthcare workers for collecting saliva specimen, the waiting time for suspected patients will be reduced. This is crucial in busy clinical settings where a large number of individuals require screening. The results of viral culture in one of the included studies showed that saliva collected from COVID-19 patients, may contain live viruses which may allow transmission of virus from person to person [9]. These finding reinforce the use of barrier-protection equipment as a control measure, for all healthcare workers in the clinic/hospital settings during the epidemic period of COVID-19. It should be mentioned that this study has several limitations. Firstly, the outbreak and detection of SARS-CoV-2 has begun very recently; therefore the available data in this regard is very scarce. Secondly the included studies of this review didn’t evaluate other factors such as severity of disease or disease progression that may impact on detection rate of the virus. Finally as all of the selected studies only included hospitalized confirmed COVID-19 patients, further studies should be performed in outpatient settings. Conclusions In conclusion, although further research is warranted as the weight of the evidence increases, saliva can be considered as a non-invasive specimen for screening SARS-CoV-2 suspected patients. This method of sampling has proper accuracy and reliability regarding viral load monitoring of SARS-CoV-2 based on RT-PCR technique. Since oropharyngeal samples may cause discomfort to patients, saliva sampling after deep cough, could be recommended as an appropriate alternative. https://idpjournal.biomedcentral.com/articles/10.1186/s40249-020-00728-w ================ <QUESTION> ======= I find the nasal swabs when I get a COVID-19 test really uncomfortable. I don't know what alternatives I have. Are there other ways to collect a sample? ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Only respond with the most direct answer possible. Do not discuss anything else. Use only information from the provided document.

What are the key points from this release?

DonorPro and CardConnect Team Up to Offer Integrated Payment Processing for Nonprofits Partnership brings payment acceptance and security to medical providers through HRP’s healthcare self-pay platform PHILADELPHIA (January 7, 2014) – CardConnect, a rapidly growing payments technology company, today announced its partnership with Health Recovery Partners (HRP), a premier provider of HIPAA compliant self-pay software solutions. HRP has added CardConnect’s Payment Gateway and CardSecure tokenization technology to its end-to-end healthcare self-pay platform, Decision Partner™. By partnering with CardConnect, HRP can now provide its customers with lower costs for credit card processing and enhanced security for protecting patients’ sensitive payment data. “With abundant changes to the healthcare industry that have increased the cost of managing self-pay accounts, medical providers are increasingly seeking an easy-to-manage and low-cost self-pay software platform,” said Jeff Shanahan, President at CardConnect. “We were very impressed by HRP’s self-pay platform and are excited to include our technology in their end-to-end solution.” For HRP, finding the right payments solution provider was crucial. “Quite frankly, payment processing has always been a pain point for healthcare providers,” said Michael Sarajian, President of Health Recovery Partners. “After learning about CardConnect’s Payment Gateway, which analyzes interchange costs to ensure our customers receive the lowest rates possible, and CardSecure, the tokenization technology trusted by Fortune 500 companies, we knew we could alleviate this pain. CardConnect has made secure payment acceptance an integral part of our end-to-end solution.” Decision Partner™ is HRP’s most patient-centric self-pay solution, centralizing an array of tools and activities to guarantee the highest collection rates – and, now with CardConnect, the lowest processing costs. Decision Partner™ allows the patient to create, or medical provider to automate, personalized payment plans based on each patient’s ability to pay, as well as segment and manage probate, litigation, bankruptcy, and no-fault auto self-pay accounts. Decision Partner™ is available to healthcare providers of all sizes. For more information, visit www.healthrecoverypartners.com. 

Only respond with the most direct answer possible. Do not discuss anything else. Use only information from the provided document. What are the key points from this release? DonorPro and CardConnect Team Up to Offer Integrated Payment Processing for Nonprofits Partnership brings payment acceptance and security to medical providers through HRP’s healthcare self-pay platform PHILADELPHIA (January 7, 2014) – CardConnect, a rapidly growing payments technology company, today announced its partnership with Health Recovery Partners (HRP), a premier provider of HIPAA compliant self-pay software solutions. HRP has added CardConnect’s Payment Gateway and CardSecure tokenization technology to its end-to-end healthcare self-pay platform, Decision Partner™. By partnering with CardConnect, HRP can now provide its customers with lower costs for credit card processing and enhanced security for protecting patients’ sensitive payment data. “With abundant changes to the healthcare industry that have increased the cost of managing self-pay accounts, medical providers are increasingly seeking an easy-to-manage and low-cost self-pay software platform,” said Jeff Shanahan, President at CardConnect. “We were very impressed by HRP’s self-pay platform and are excited to include our technology in their end-to-end solution.” For HRP, finding the right payments solution provider was crucial. “Quite frankly, payment processing has always been a pain point for healthcare providers,” said Michael Sarajian, President of Health Recovery Partners. “After learning about CardConnect’s Payment Gateway, which analyzes interchange costs to ensure our customers receive the lowest rates possible, and CardSecure, the tokenization technology trusted by Fortune 500 companies, we knew we could alleviate this pain. CardConnect has made secure payment acceptance an integral part of our end-to-end solution.” Decision Partner™ is HRP’s most patient-centric self-pay solution, centralizing an array of tools and activities to guarantee the highest collection rates – and, now with CardConnect, the lowest processing costs. Decision Partner™ allows the patient to create, or medical provider to automate, personalized payment plans based on each patient’s ability to pay, as well as segment and manage probate, litigation, bankruptcy, and no-fault auto self-pay accounts. Decision Partner™ is available to healthcare providers of all sizes. For more information, visit www.healthrecoverypartners.com. 

No information from beyond the provided context block can be used in formulating your answer. Formulate your response using full paragraphs.

Provide a summary of all of the facets that are checked for compliance.

2 General Principles and Legality Checking 3.2.1 Objective of Article 3 An important objective of the Regulations in Article 3 is to enable cars to race closely, by ensuring that the aerodynamic performance loss of a car following another car is kept to a minimum. In order to verify whether this objective has been achieved, Competitors may be required on request to supply the FIA with any relevant information. 2024 Formula 1 Technical Regulations 13 25 April 2023 © 2023 Fédération Internationale de l’Automobile Issue 1 In any case the Intellectual Property of this information, will remain the property of the Competitor, will be protected and not divulged to any third party. 3.2.2 Aerodynamic Influence With the exception of the driver adjustable bodywork described in Article 3.10.10 (in addition to minimal parts solely associated with its actuation) and the flexible seals specifically permitted by Articles 3.13 and 3.14.4, all aerodynamic components or bodywork influencing the car’s aerodynamic performance must be rigidly secured and immobile with respect to their frame of reference defined in Article 3.3. Furthermore, these components must produce a uniform, solid, hard, continuous, impervious surface under all circumstances. Any device or construction that is designed to bridge the gap between the sprung part of the car and the ground is prohibited under all circumstances. With the exception of the parts necessary for the adjustment described in Article 3.10.10, or any incidental movement due to the steering system, any car system, device or procedure which uses driver movement as a means of altering the aerodynamic characteristics of the car is prohibited. The Aerodynamic influence of any component of the car not considered to be bodywork must be incidental to its main function. Any design which aims to maximise such an aerodynamic influence is prohibited. 3.2.3 Symmetry All bodywork must be nominally symmetrical with respect to Y=0. Consequently, and unless otherwise specified, any regulation in Article 3 concerning one side of the car will be assumed to be valid for the other side of the car and references to maximum permissible numbers of components in Article 3 will also refer to the one side of the car. Minimal exceptions to the requirement of symmetry of this Article will be accepted for the installation of non-symmetrical mechanical components of the car, for asymmetrical cooling requirements or for asymmetrical angle adjustment of the front flap defined in Article 3.9.7. Bodywork on the unsprung mass must respect this Article when the suspension position of each wheel is virtually re-orientated so that its wheel coordinate system axes (described in Article 2.11.3) are parallel to their respective axis of the car coordinate system (described in Article 2.11.1). 3.2.4 Digital legality checking The assessment of the car’s compliance with the Aerodynamic Regulations will be carried out digitally using CAD models provided by the teams. In these models: a. Components may only be designed to the edge of a Reference Volume or with a precise geometrical feature, or to the limit of a geometrical criterion (save for the normal round-off discrepancies of the CAD system), when the regulations specifically require an aspect of the bodywork to be designed to this limit, or it can be demonstrated that the design does not rely on lying exactly on this limit to conform to the regulations, such that it is possible for the physical bodywork to comply. b. Components which must follow a precise shape, surface or plane must be designed without any tolerance, save for the normal round-off discrepancies of the CAD system. 3.2.5 Physical legality checking The cars may be measured during a Competition in order to check their conformance to the CAD models discussed in Article 3.2.4 and to ensure they remain inside the Reference Volumes. a. Unless otherwise specified, a tolerance of ±3mm will be accepted for manufacturing purposes only with respect to the CAD surfaces. Where measured surfaces lie outside of this tolerance but remain within the Reference Volumes, a Competitor may be required to provide additional information (e.g. revised CAD geometry) to demonstrate compliance with the regulations. Any discrepancies contrived to create a special aerodynamic effect or surface finish will not be permitted. 2024 Formula 1 Technical Regulations 14 25 April 2023 © 2023 Fédération Internationale de l’Automobile Issue 1 b. Irrespective of a), geometrical discrepancies at the limits of the Reference Volumes must be such that the measured component remains inside the Reference Volume. c. A positional tolerance of +/- 2mm will be accepted for the Front Wing Bodywork, Rear Wing Bodywork, Exhaust Tailpipe, Floor Bodywork behind XR=0, and Tail. This will be assessed by realigning each of the groups of Reference Volumes and Reference Surfaces that define the assemblies, by up to 2mm from their original position, to best fit the measured geometry. d. Irrespective of b), a tolerance of Z=+/-2mm will be accepted for parts of the car lying on the Z=0 plane, with -375 ≤ Y ≤ 375 and ahead of XR=0. e. Minimal discrepancies from the CAD surfaces will also be accepted in the following cases: i. Minimal repairs carried out on aerodynamic components and approved by the FIA ii. Tape, provided it does not achieve an aerodynamic effect otherwise not permitted by Article 3 iii. Junctions between bodywork panels iv. Local bodywork fixing details 3.2.6 Datum Points All cars must be equipped with mountings for optical targets that enable the car’s datum to be determined for scrutineering in the following locations: i. One on the forward part of the top of the survival cell. ii. Two positioned symmetrically about Y=0 on the top of the survival cell close to XB=0. iii. Two positioned symmetrically about Y=0 on the side of the survival cell close to XB=0. iv. Two positioned symmetrically about Y=0 on the side of the survival cell close to the rear mounts of the secondary roll structure. v. Two positioned symmetrically about Y=0 within an axis-aligned cuboid with an interior diagonal defined by points [XC=0, 175, 970] and [XC=150, -175, 870]. vi. One probed point on the RIS or gearbox case. In all cases, a file with required datum points must be supplied for each survival cell. For deflection testing, all cars must be provided with a means of mounting a reference artefact to the RIS. This mounting may be temporary, but must be rigid with respect to the underlying car structure. Full details of the requirements are given in the Appendix the Technical and Sporting Regulations. 3.2.7 Section titles and Article titles within this article have no regulatory value. 3.2.8 Static pressure tappings are permitted in surfaces, provided that they; i. Have an internal diameter of no more than 2mm. ii. They are flush with the underlying geometry. iii. Are only connected to pressure sensors, or are blanked, without leakage. 3.3.1 Bodywork which is part of the sprung mass of the car The only sprung mass bodywork permitted is that defined under Articles 3.5 to 3.12 and under Articles 3.1.1.a.ii to iv. The frame of reference for every part of the car classified as Sprung Mass Bodywork is the coordinate system defined in Article 2.11.1. Any bodywork that is trimmed or filleted in Article 3.11 must first be declared as belonging to one of the groups defined in Articles 3.5 to 3.10. Unless otherwise stated, the compliance of an individual bodywork group to Article 3 will be assessed independently and prior to any trimming, filleting and assembly operation referred to in Article 3.11, and the FIA may request to see any discarded geometry after final assembly. Once the final assembly is completed, any bodywork surfaces no longer exposed to an external airstream or internal duct may be modified, providing they remain unexposed. 3.3.2 Wheel Bodywork The only wheel bodywork permitted is that defined under Article 3.13. With the exception of wheel covers, as defined in Article 3.13.7, the frame of reference for every part of the car classified as Wheel Bodywork is the corresponding upright structure and the corresponding coordinate system defined in Article 2.11.3. The frame of reference for any wheel cover, as defined in Article 3.13.7 is the corresponding wheel rim. 3.3.3 Suspension Fairings The only suspension fairings permitted are those defined under Article 3.14. In order to assess compliance with Article 3.2.2, the frame of reference of any suspension fairing is the structural suspension member that it is attached to.

System Instructions: No information from beyond the provided context block can be used in formulating your answer. Formulate your response using full paragraphs. Question: Provide a summary of all of the facets that are checked for compliance. Context Block: 2 General Principles and Legality Checking 3.2.1 Objective of Article 3 An important objective of the Regulations in Article 3 is to enable cars to race closely, by ensuring that the aerodynamic performance loss of a car following another car is kept to a minimum. In order to verify whether this objective has been achieved, Competitors may be required on request to supply the FIA with any relevant information. 2024 Formula 1 Technical Regulations 13 25 April 2023 © 2023 Fédération Internationale de l’Automobile Issue 1 In any case the Intellectual Property of this information, will remain the property of the Competitor, will be protected and not divulged to any third party. 3.2.2 Aerodynamic Influence With the exception of the driver adjustable bodywork described in Article 3.10.10 (in addition to minimal parts solely associated with its actuation) and the flexible seals specifically permitted by Articles 3.13 and 3.14.4, all aerodynamic components or bodywork influencing the car’s aerodynamic performance must be rigidly secured and immobile with respect to their frame of reference defined in Article 3.3. Furthermore, these components must produce a uniform, solid, hard, continuous, impervious surface under all circumstances. Any device or construction that is designed to bridge the gap between the sprung part of the car and the ground is prohibited under all circumstances. With the exception of the parts necessary for the adjustment described in Article 3.10.10, or any incidental movement due to the steering system, any car system, device or procedure which uses driver movement as a means of altering the aerodynamic characteristics of the car is prohibited. The Aerodynamic influence of any component of the car not considered to be bodywork must be incidental to its main function. Any design which aims to maximise such an aerodynamic influence is prohibited. 3.2.3 Symmetry All bodywork must be nominally symmetrical with respect to Y=0. Consequently, and unless otherwise specified, any regulation in Article 3 concerning one side of the car will be assumed to be valid for the other side of the car and references to maximum permissible numbers of components in Article 3 will also refer to the one side of the car. Minimal exceptions to the requirement of symmetry of this Article will be accepted for the installation of non-symmetrical mechanical components of the car, for asymmetrical cooling requirements or for asymmetrical angle adjustment of the front flap defined in Article 3.9.7. Bodywork on the unsprung mass must respect this Article when the suspension position of each wheel is virtually re-orientated so that its wheel coordinate system axes (described in Article 2.11.3) are parallel to their respective axis of the car coordinate system (described in Article 2.11.1). 3.2.4 Digital legality checking The assessment of the car’s compliance with the Aerodynamic Regulations will be carried out digitally using CAD models provided by the teams. In these models: a. Components may only be designed to the edge of a Reference Volume or with a precise geometrical feature, or to the limit of a geometrical criterion (save for the normal round-off discrepancies of the CAD system), when the regulations specifically require an aspect of the bodywork to be designed to this limit, or it can be demonstrated that the design does not rely on lying exactly on this limit to conform to the regulations, such that it is possible for the physical bodywork to comply. b. Components which must follow a precise shape, surface or plane must be designed without any tolerance, save for the normal round-off discrepancies of the CAD system. 3.2.5 Physical legality checking The cars may be measured during a Competition in order to check their conformance to the CAD models discussed in Article 3.2.4 and to ensure they remain inside the Reference Volumes. a. Unless otherwise specified, a tolerance of ±3mm will be accepted for manufacturing purposes only with respect to the CAD surfaces. Where measured surfaces lie outside of this tolerance but remain within the Reference Volumes, a Competitor may be required to provide additional information (e.g. revised CAD geometry) to demonstrate compliance with the regulations. Any discrepancies contrived to create a special aerodynamic effect or surface finish will not be permitted. 2024 Formula 1 Technical Regulations 14 25 April 2023 © 2023 Fédération Internationale de l’Automobile Issue 1 b. Irrespective of a), geometrical discrepancies at the limits of the Reference Volumes must be such that the measured component remains inside the Reference Volume. c. A positional tolerance of +/- 2mm will be accepted for the Front Wing Bodywork, Rear Wing Bodywork, Exhaust Tailpipe, Floor Bodywork behind XR=0, and Tail. This will be assessed by realigning each of the groups of Reference Volumes and Reference Surfaces that define the assemblies, by up to 2mm from their original position, to best fit the measured geometry. d. Irrespective of b), a tolerance of Z=+/-2mm will be accepted for parts of the car lying on the Z=0 plane, with -375 ≤ Y ≤ 375 and ahead of XR=0. e. Minimal discrepancies from the CAD surfaces will also be accepted in the following cases: i. Minimal repairs carried out on aerodynamic components and approved by the FIA ii. Tape, provided it does not achieve an aerodynamic effect otherwise not permitted by Article 3 iii. Junctions between bodywork panels iv. Local bodywork fixing details 3.2.6 Datum Points All cars must be equipped with mountings for optical targets that enable the car’s datum to be determined for scrutineering in the following locations: i. One on the forward part of the top of the survival cell. ii. Two positioned symmetrically about Y=0 on the top of the survival cell close to XB=0. iii. Two positioned symmetrically about Y=0 on the side of the survival cell close to XB=0. iv. Two positioned symmetrically about Y=0 on the side of the survival cell close to the rear mounts of the secondary roll structure. v. Two positioned symmetrically about Y=0 within an axis-aligned cuboid with an interior diagonal defined by points [XC=0, 175, 970] and [XC=150, -175, 870]. vi. One probed point on the RIS or gearbox case. In all cases, a file with required datum points must be supplied for each survival cell. For deflection testing, all cars must be provided with a means of mounting a reference artefact to the RIS. This mounting may be temporary, but must be rigid with respect to the underlying car structure. Full details of the requirements are given in the Appendix the Technical and Sporting Regulations. 3.2.7 Section titles and Article titles within this article have no regulatory value. 3.2.8 Static pressure tappings are permitted in surfaces, provided that they; i. Have an internal diameter of no more than 2mm. ii. They are flush with the underlying geometry. iii. Are only connected to pressure sensors, or are blanked, without leakage. 3.3.1 Bodywork which is part of the sprung mass of the car The only sprung mass bodywork permitted is that defined under Articles 3.5 to 3.12 and under Articles 3.1.1.a.ii to iv. The frame of reference for every part of the car classified as Sprung Mass Bodywork is the coordinate system defined in Article 2.11.1. Any bodywork that is trimmed or filleted in Article 3.11 must first be declared as belonging to one of the groups defined in Articles 3.5 to 3.10. Unless otherwise stated, the compliance of an individual bodywork group to Article 3 will be assessed independently and prior to any trimming, filleting and assembly operation referred to in Article 3.11, and the FIA may request to see any discarded geometry after final assembly. Once the final assembly is completed, any bodywork surfaces no longer exposed to an external airstream or internal duct may be modified, providing they remain unexposed. 3.3.2 Wheel Bodywork The only wheel bodywork permitted is that defined under Article 3.13. With the exception of wheel covers, as defined in Article 3.13.7, the frame of reference for every part of the car classified as Wheel Bodywork is the corresponding upright structure and the corresponding coordinate system defined in Article 2.11.3. The frame of reference for any wheel cover, as defined in Article 3.13.7 is the corresponding wheel rim. 3.3.3 Suspension Fairings The only suspension fairings permitted are those defined under Article 3.14. In order to assess compliance with Article 3.2.2, the frame of reference of any suspension fairing is the structural suspension member that it is attached to.

Create your answer using only information found in the given context.

What are some factors that stop people from eating meat?

Recent research has identified the major motivations and constraints around vegetarian and vegan diets [30 ]. The main motivations to move towards a vegetarian or vegan diet are animal welfare, the environment and personal health, whilst the major barriers are sensory enjoyment of animal Sustainability 2019, 11, 6844 3 of 17 products, convenience and financial cost [ 30 ]. Mullee et al. [31 ] found that, when asked about possible reasons for eating a more vegetarian diet, the most popular option chosen by omnivores and semivegetarians was their health. The environment and animal welfare were chosen by fewer participants, and for omnivores, these reasons ranked below ‘to discover new tastes’, ‘to reduce weight’, and ‘no reason’. This finding has been replicated elsewhere [32 ,33 ] and implies that, for those not currently reducing their meat consumption, potential personal benefits are more important than environmental or ethical benefits. More specifically, consumers often recognise health benefits such as decreased saturated fat intake, increased fruit and vegetable intake and disease prevention [ 32, 34]. On the other hand, some worry about not getting enough protein or iron from a vegetarian diet [35]. Interestingly, this prioritisation of health motives appears to be reversed for vegetarians and vegans. According to a survey published by Humane League Labs [36], whilst health and nutrition reasons for reducing animal product consumption are the most commonly cited by omnivores and semivegetarians, animal welfare is the most common reason given by vegetarians and vegans. This is logical, because improving one’s health or reducing one’s environmental impact can be achieved by consuming incrementally fewer animal products; viewing animal products as the product of animal suffering and exploitation, however, is more conducive to eschewing them altogether. In a systematic review of consumer perceptions of sustainable protein consumption, Hartmann and Siegrist [37 ] found that it is common for consumers to underestimate the ecological impact of meat consumption. This has been observed in many different studies [33 ,38 – 40 ] and may imply a lack of knowledge about the environmental impact of meat consumption. Alternatively, this could reflect that consumers are generally unwilling to reduce their meat consumption [40 ] and are subsequently motivated to minimise their perceptions of the negative consequences of their choices [41]. Indeed, such motivated reasoning appears to be evident with respect to animal welfare issues. Most people eat meat but disapprove of harming animals, a conflict that has been dubbed ‘the meat paradox’ [42 ]. Rothgerber [ 43] identified a number of ways in which dissonance around harming animals arises in meat-eaters, and a number of strategies which are used to reduce this dissonance. Dissonance-reducing strategies include denial of animal mind, denial of animals’ ability to feel pain and dissociating meat from its animal origin [ 43 ]. This motivated reasoning results in a number of odd conclusions, such as lower mental capacity being ascribed to food animals compared to nonfood animals and increased denial of animal mind when one anticipates immediate meat consumption [ 44]. One can understand the motivation to continue eating animal products; the literature has identified several considerable constraints to adopting a vegetarian or vegan diet. Studies have consistently found that the strongest of these is simply enjoyment of eating meat [34 , 45, 46]. This was by far the number one reason for not being vegetarian in a recent UK survey [ 47 ] and was the biggest constraint for online survey respondents who indicated that they do not want to go vegetarian or vegan [ 36]. Despite the many potential benefits, the taste of meat and animal products is enough of a barrier to prevent dietary change for most people. The second most important barrier is convenience, with many consumers saying vegetarian dishes are difficult to prepare and that there is a lack of options when eating out [ 33 ,38 ,48 ]. Humane League Labs [36 ] found that a lack of options when eating out was the most common factor that people said made it difficult to eat meat-free meals, whilst Schenk, Rössel and Scholz [30 ] have argued that the additional time, knowledge and effort required to buy and prepare vegetarian or vegan food is especially a barrier to those newly transitioning diets. Finally, for some, there is a financial barrier [49], although there is considerably less consensus on this in the literature [30]. A UK survey found that the high cost of meat substitutes was a barrier for 58% of consumers, though this survey conducted by VoucherCodesPro [ 47 ] may have been inclined to focus on financial considerations. Another study found that a vegetarian diet is actually cheaper than one containing meat, but that a vegan diet is most expensive of all [ 22 ]. This may be due to the relatively high cost of plant-based milks and other specialist products. Sustainability 2019, 11, 6844 4 of 17 The present study investigates UK meat-eaters’ views of various aspects of vegetarianism and veganism. Whilst the common motivators and constraints to vegetarian and vegan diets are well documented, there is a paucity of open data assessing how meat-eaters evaluate the relevant aspects of each of these diets. This study seeks to address this gap by providing quantitative evaluations of the relevant aspects of vegetarian and vegan diets. Additionally, there is currently no quantitative comparison of these factors with respect to vegetarianism versus veganism. Therefore, this study compares ratings of common motivators and barriers between vegetarian and vegan diets. Finally, little is known about how these evaluations of vegetarian and vegan diets vary amongst different demographic groups. Therefore, this study examines the overall mean ratings of each of these factors and investigates how these views vary between different demographics. 2. Methods 2.1. Participants Meat-eaters living in the UK aged 18 and over were recruited (n = 1000). Participants were recruited through the online research platform, Prolific, and each participant was paid £0.45 for a 5 min survey. Recruiting participants through this type of online platform has its limitations, including the possibility of recruiting an unrepresentative sample, and asking questions in a contrived setting which may not be ecologically valid [ 50]. Nonetheless, this sampling technique does offer low cost and fast recruitment of specifiable samples, and the use of Prolific as a recruitment tool in academic research is therefore increasingly common and generally considered acceptable [51 –53 ]. Although recruitment was for meat-eaters only, there was a small number of vegetarians in the original dataset (n = 25); these participants were removed, and their responses were replaced with more meat-eaters. The final sample was 49.8% male and 49.8% female (0.3% did not disclose gender, 0.1% ‘other’), and the mean age was 34.02 (SD = 11.67). 2.2. Procedure This study received ethical approval from the University of Bath’s Department of Psychology Ethics Committee (PREC 18-219). The full anonymised dataset is available via OSF (see Supplementary Materials). First, participants read some brief information about the study and gave their consent to take part. They were then given definitions of vegetarianism and veganism and asked to give their opinions about 11 different aspects of vegetarian and vegan diets using 7-point bipolar scales. The order of these scales and the order in which participants were asked about vegetarianism and veganism were randomised to control for order effects. Next, participants answered questions about their intended consumption of meat and their intended consumption of animal products ‘one month from today’. On 6-point scales, participants could indicate that they would eliminate, greatly reduce, slightly reduce, maintain about the same, slightly increase or greatly increase their consumption of both meat, and animal products generally. Similar scales have been used in previous research [54,55]. It is worth noting that this measure is conservative. Compared to asking about intentions to reduce consumption in general, defining a specific action and a specific, short time period is likely to make participants reflect critically about their own likely behaviour. Additionally, as participants answered this question, they saw the phrase ‘Thank you for being honest!’ which was intended to mitigate the social desirability effect (i.e., over-reporting of intentions to reduce animal product consumption). Finally, participants gave demographic information, including their age, gender, political orientation, education and income. They also indicated whether they ate ‘at least occasionally’ beef, lamb, pork, chicken, fish, eggs and dairy. Participants were then debriefed and compensated.

What are some factors that stop people from eating meat? Create your answer using only information found in the given context. Recent research has identified the major motivations and constraints around vegetarian and vegan diets [30 ]. The main motivations to move towards a vegetarian or vegan diet are animal welfare, the environment and personal health, whilst the major barriers are sensory enjoyment of animal products, convenience and financial cost [ 30 ]. Mullee et al. [31 ] found that, when asked about possible reasons for eating a more vegetarian diet, the most popular option chosen by omnivores and semivegetarians was their health. The environment and animal welfare were chosen by fewer participants, and for omnivores, these reasons ranked below ‘to discover new tastes’, ‘to reduce weight’, and ‘no reason’. This finding has been replicated elsewhere [32 ,33 ] and implies that, for those not currently reducing their meat consumption, potential personal benefits are more important than environmental or ethical benefits. More specifically, consumers often recognise health benefits such as decreased saturated fat intake, increased fruit and vegetable intake and disease prevention [ 32, 34]. On the other hand, some worry about not getting enough protein or iron from a vegetarian diet [35]. Interestingly, this prioritisation of health motives appears to be reversed for vegetarians and vegans. According to a survey published by Humane League Labs [36], whilst health and nutrition reasons for reducing animal product consumption are the most commonly cited by omnivores and semivegetarians, animal welfare is the most common reason given by vegetarians and vegans. This is logical, because improving one’s health or reducing one’s environmental impact can be achieved by consuming incrementally fewer animal products; viewing animal products as the product of animal suffering and exploitation, however, is more conducive to eschewing them altogether. In a systematic review of consumer perceptions of sustainable protein consumption, Hartmann and Siegrist [37 ] found that it is common for consumers to underestimate the ecological impact of meat consumption. This has been observed in many different studies [33 ,38 – 40 ] and may imply a lack of knowledge about the environmental impact of meat consumption. Alternatively, this could reflect that consumers are generally unwilling to reduce their meat consumption [40 ] and are subsequently motivated to minimise their perceptions of the negative consequences of their choices [41]. Indeed, such motivated reasoning appears to be evident with respect to animal welfare issues. Most people eat meat but disapprove of harming animals, a conflict that has been dubbed ‘the meat paradox’ [42 ]. Rothgerber [ 43] identified a number of ways in which dissonance around harming animals arises in meat-eaters, and a number of strategies which are used to reduce this dissonance. Dissonance-reducing strategies include denial of animal mind, denial of animals’ ability to feel pain and dissociating meat from its animal origin [ 43 ]. This motivated reasoning results in a number of odd conclusions, such as lower mental capacity being ascribed to food animals compared to nonfood animals and increased denial of animal mind when one anticipates immediate meat consumption [ 44]. One can understand the motivation to continue eating animal products; the literature has identified several considerable constraints to adopting a vegetarian or vegan diet. Studies have consistently found that the strongest of these is simply enjoyment of eating meat [34 , 45, 46]. This was by far the number one reason for not being vegetarian in a recent UK survey [ 47 ] and was the biggest constraint for online survey respondents who indicated that they do not want to go vegetarian or vegan [ 36]. Despite the many potential benefits, the taste of meat and animal products is enough of a barrier to prevent dietary change for most people. The second most important barrier is convenience, with many consumers saying vegetarian dishes are difficult to prepare and that there is a lack of options when eating out [ 33 ,38 ,48 ]. Humane League Labs [36 ] found that a lack of options when eating out was the most common factor that people said made it difficult to eat meat-free meals, whilst Schenk, Rössel and Scholz [30 ] have argued that the additional time, knowledge and effort required to buy and prepare vegetarian or vegan food is especially a barrier to those newly transitioning diets. Finally, for some, there is a financial barrier [49], although there is considerably less consensus on this in the literature [30]. A UK survey found that the high cost of meat substitutes was a barrier for 58% of consumers, though this survey conducted by VoucherCodesPro [ 47 ] may have been inclined to focus on financial considerations. Another study found that a vegetarian diet is actually cheaper than one containing meat, but that a vegan diet is most expensive of all [ 22 ]. This may be due to the relatively high cost of plant-based milks and other specialist products. The present study investigates UK meat-eaters’ views of various aspects of vegetarianism and veganism. Whilst the common motivators and constraints to vegetarian and vegan diets are well documented, there is a paucity of open data assessing how meat-eaters evaluate the relevant aspects of each of these diets. This study seeks to address this gap by providing quantitative evaluations of the relevant aspects of vegetarian and vegan diets. Additionally, there is currently no quantitative comparison of these factors with respect to vegetarianism versus veganism. Therefore, this study compares ratings of common motivators and barriers between vegetarian and vegan diets. Finally, little is known about how these evaluations of vegetarian and vegan diets vary amongst different demographic groups. Therefore, this study examines the overall mean ratings of each of these factors and investigates how these views vary between different demographics. 2. Methods 2.1. Participants Meat-eaters living in the UK aged 18 and over were recruited (n = 1000). Participants were recruited through the online research platform, Prolific, and each participant was paid £0.45 for a 5 min survey. Recruiting participants through this type of online platform has its limitations, including the possibility of recruiting an unrepresentative sample, and asking questions in a contrived setting which may not be ecologically valid [ 50]. Nonetheless, this sampling technique does offer low cost and fast recruitment of specifiable samples, and the use of Prolific as a recruitment tool in academic research is therefore increasingly common and generally considered acceptable [51 –53 ]. Although recruitment was for meat-eaters only, there was a small number of vegetarians in the original dataset (n = 25); these participants were removed, and their responses were replaced with more meat-eaters. The final sample was 49.8% male and 49.8% female (0.3% did not disclose gender, 0.1% ‘other’), and the mean age was 34.02 (SD = 11.67). 2.2. Procedure This study received ethical approval from the University of Bath’s Department of Psychology Ethics Committee (PREC 18-219). The full anonymised dataset is available via OSF (see Supplementary Materials). First, participants read some brief information about the study and gave their consent to take part. They were then given definitions of vegetarianism and veganism and asked to give their opinions about 11 different aspects of vegetarian and vegan diets using 7-point bipolar scales. The order of these scales and the order in which participants were asked about vegetarianism and veganism were randomised to control for order effects. Next, participants answered questions about their intended consumption of meat and their intended consumption of animal products ‘one month from today’. On 6-point scales, participants could indicate that they would eliminate, greatly reduce, slightly reduce, maintain about the same, slightly increase or greatly increase their consumption of both meat, and animal products generally. Similar scales have been used in previous research [54,55]. It is worth noting that this measure is conservative. Compared to asking about intentions to reduce consumption in general, defining a specific action and a specific, short time period is likely to make participants reflect critically about their own likely behaviour. Additionally, as participants answered this question, they saw the phrase ‘Thank you for being honest!’ which was intended to mitigate the social desirability effect (i.e., over-reporting of intentions to reduce animal product consumption). Finally, participants gave demographic information, including their age, gender, political orientation, education and income. They also indicated whether they ate ‘at least occasionally’ beef, lamb, pork, chicken, fish, eggs and dairy. Participants were then debriefed and compensated.

Please base your answer on the information provided in this document only. Do not embellish your response or add any details that are unnecessary to answer the question. Use simple words and avoid any jargon that may be foreign to the layman.

What figures are given to indicate the rising use of cannabis consumption in the United States?

**Study of smoking cannabis in adults EXCERPT** Abstract Background We examined the association between cannabis use and cardiovascular outcomes among the general population, among never‐tobacco smokers, and among younger individuals. Conclusions Cannabis use is associated with adverse cardiovascular outcomes, with heavier use (more days per month) associated with higher odds of adverse outcomes. Clinical Perspective What Is New? Cannabis use is associated with increased risk of myocardial infarction and stroke, with higher odds of events associated with more days of use per month, controlling for demographic factors and tobacco smoking. Similar increases in risk associated with cannabis use are found in never‐tobacco smokers. What Are the Clinical Implications? Patients should be screened for cannabis use and advised to avoid smoking cannabis to reduce their risk of premature cardiovascular disease and cardiac events. Nonstandard Abbreviations and Acronyms BRFSS Behavioral Risk Factor Surveillance System Cannabis use is increasing in the US population.1 From 2002 to 2019, past‐year prevalence of US adult cannabis use increased from 10.4% to 18.0%, whereas daily/almost daily use (300+ days per year) increased from 1.3% to 3.9%. Rising diagnoses of cannabis use disorder suggest that this increase in use is not confined to reporting of use.2, 3 At the same time, perceptions of the harmfulness of cannabis are decreasing. National surveys reported that adult belief in great risk of weekly cannabis use fell from 50% in 2002 to 28.6% in 2019.4 Despite common use, little is known about the risks of cannabis use and, in particular, the cardiovascular disease risks. Cardiovascular‐related death is the leading cause of mortality, and cannabis use could be an important, unappreciated risk factor leading to many preventable deaths.5 There are reasons to believe that cannabis use is associated with atherosclerotic heart disease. Endocannabinoid receptors are ubiquitous throughout the cardiovascular system.6 Tetrahydrocannabinol, the active component of cannabis, has hemodynamic effects and may result in syncope, stroke, and myocardial infarction.7, 8, 9 Smoking, the predominant method of cannabis use,10 may pose additional cardiovascular risks as a result of inhalation of particulate matter.11 Furthermore, studies in rats have demonstrated that secondhand cannabis smoke exposure is associated with endothelial dysfunction, a precursor to cardiovascular disease.11 Past studies on the association between cannabis use and cardiovascular outcomes have been limited by the dearth of adults with frequent cannabis use.7, 12, 13 Moreover, most studies have been in younger populations at low risk for cardiovascular disease, and therefore without sufficient power to detect an association between cannabis use and atherosclerotic heart disease outcomes.7, 12, 14 In addition, tobacco use among adults who use cannabis is common, and small sample sizes prevented analyses on the association of cannabis use with cardiovascular outcomes among nontobacco users. Any independent effects of cannabis and tobacco in the general adult population and effects of cannabis use among those who have never smoked tobacco cigarettes is of interest, because some have questioned whether cannabis has any effect beyond that of being associated with concurrent tobacco use.15, 16, 17 The National Academy of Sciences report on the health effects of cannabis use suggested that “testing the interaction between cannabis and tobacco use and performing stratified analyses to test the association of cannabis use with clinical endpoints in nonusers of tobacco” is necessary to elucidate the effect of cannabis use on cardiovascular health independent of tobacco use.12 We performed these tests and controlled for potential confounders. The Behavioral Risk Factor Surveillance System (BRFSS) is a national cross‐sectional survey performed annually by the Centers for Disease Control and Prevention. Beginning in 2016, an optional cannabis module was included supporting an analysis examining the association of cannabis use with cardiovascular outcomes.18 Although there have been 3 other studies examining the association of cannabis use with cardiovascular events using the BRFSS cannabis module,19, 20, 21 our much larger sample size enabled us to investigate whether cannabis use was associated with atherosclerotic heart disease outcomes among the general adult population, among nontobacco cigarette users, and among younger adults. Methods Study Sample We combined 2016 to 2020 BRFSS data from 27 American states and 2 territories participating in the cannabis module during at least 1 of these years (Table S1). BRFSS is a telephone survey that collects data from a representative sample of US adults on risk factors, chronic conditions, and health care access.18 The BRFSS questions used are summarized in Table S2. Because this study was based on publicly available data and exempt from institutional review board review, informed consent was not obtained. The data and corresponding materials that support the findings of this study are available from the corresponding author upon request. Our sample included those 18 to 74 years old from the BRFSS (N=434 104) who answered the question, “During the past 30 days, on how many days did you use marijuana or hashish?”, excluding (<1%) those who answered “Don't know” or refused to answer. We excluded adults >74 years old because cannabis use is uncommon in this population. Measures We quantified cannabis use as a continuous variable, days of cannabis use in the past 30 days divided by 30. Thus, daily cannabis use is scored 1, and less than daily use scores were proportionately lower. Specifically, daily use was scored as 1=30/30, 15 days per month was scored 0.5=15/30, and nonuse was scored 0=(0/30). Nonusers’ score was 0. Therefore, a 1‐unit change in our cannabis use frequency metric is equivalent to a comparison of 0 days of cannabis use within past 30 days to daily cannabis use. Demographic variables included age, sex, and self‐identified race and ethnicity. Socioeconomic status was represented by educational attainment, categorized as less than high school, high school, some college, or college graduate. Cardiovascular risk factors included tobacco cigarette use (never, former, current), current alcohol consumption (nonuse, nondaily use, daily use), body mass index, diabetes, and physical activity. Nicotine e‐cigarette use was similarly classified as never, former, or current. Outcomes were assessed when respondents were asked, “Has a doctor, nurse, or other health professional ever told you that you had any of the following….?”. Coronary heart disease (CHD) was assessed by: “(Ever told) you had angina or coronary heart disease?” The lifetime occurrence of myocardial infarction (MI): “(Ever told) you had a heart attack, also called a myocardial infarction?” Stroke: “(Ever told) you had a stroke?” Finally, we created composite indicator for cardiovascular disease, which included any CHD, MI, or stroke. Statistical Analysis Complete case‐weighted estimates of demographic and socioeconomic factors, health behaviors, and chronic conditions were calculated using survey strata, primary sampling units clusters, and sampling weights for the 5 years of combined data to obtain nationally representative results for the states using the cannabis module.22P values for bivariate analyses were calculated by the Rao‐Scott corrected χ2 test. We conducted 3 multivariable logistic analyses of the association of lifetime occurrence of CHD, MI, stroke, and the composite of the 3 with cannabis use ([days per month]/30) as a function of demographic and socioeconomic factors, health‐related behaviors, and other chronic conditions, accounting for the complex survey design. The first analysis included the entire sample 18 to 74 years old controlling for tobacco cigarette use and other covariates. The second was conducted among the respondents who had never used tobacco cigarettes. The third was conducted among respondents who had never used tobacco cigarettes or e‐cigarettes. In the first analysis, we tested for an interaction between current cannabis use (any cannabis use frequency between 1 and 30 days) and current tobacco cigarette use to see if there were synergistic effects of cannabis and conventional tobacco use by measuring the coefficient. An interaction was coded as present if frequency of cannabis use was at least 1 day per month, and conventional tobacco use was coded as current. In addition, we examined the variance inflation factors for the cannabis and tobacco use variables to ensure that they were quantifying statistically independent effects. An upper bound of 5 for the variance inflation factor was used for determination of independent effects.23 We performed supplemental analyses restricting the 3 main analyses to younger adults at risk for premature cardiovascular disease, which we defined as men <55 years old and women <65 years old. The difference in age cutoff by sex is due to the protective effect of estrogen.24 We also conducted sensitivity analyses limiting the comparison to daily versus nonusers using the same multivariate model as in the main analysis and using propensity‐score matching (details in Data S1). We used R statistical software version 4.0 (R Core Team, 2020, Vienna, Austria) and survey package to produce complex survey‐adjusted statistics.25, 26 We used the package car to estimate the survey‐adjusted variance inflation factors.27 Results Baseline Characteristics Among the 434 104 respondents 18 to 74 years old who answered the cannabis module, the weighted prevalence of daily cannabis use was 4.0%, nondaily use was 7.1% (median: 5 days per month; interquartile range, 2–14), and nonuse was 88.9%. The most common form of cannabis consumption was smoking (73.8% of current users). The mean age of the respondents was 45.4 years. About half (51.1%) were women, and the majority of the respondents were White (60.2%), whereas 11.6% were Black, 19.3% Hispanic, and 8.9% other race and ethnicity (eg, non‐Hispanic Asian, Native American, Native Hawaiian and Pacific Islander, and those self‐reporting as multiracial) (Table 1). Daily alcohol use and physical activity had a prevalence of 4.3% and 75.0%, respectively. Most of the sample had never used tobacco cigarettes (61.1%). The prevalence of CHD, MI, stroke, and the composite outcome of all 3 were 3.5% (N=20 009), 3.6% (N=20 563), 2.8% (N=14 922), and 7.4% (N=40 759), respectively. The percentage of missing values for each variable was <1% of the total sample size except for race (1.64%) and alcohol use (1.06%).

question: What figures are given to indicate the rising use of cannabis consumption in the United States? task: Please base your answer on the information provided in this document only. Do not embellish your response or add any details that are unnecessary to answer the question. Use simple words and avoid any jargon that may be foreign to the layman. document: **Study of smoking cannabis in adults EXCERPT** Abstract Background We examined the association between cannabis use and cardiovascular outcomes among the general population, among never‐tobacco smokers, and among younger individuals. Conclusions Cannabis use is associated with adverse cardiovascular outcomes, with heavier use (more days per month) associated with higher odds of adverse outcomes. Clinical Perspective What Is New? Cannabis use is associated with increased risk of myocardial infarction and stroke, with higher odds of events associated with more days of use per month, controlling for demographic factors and tobacco smoking. Similar increases in risk associated with cannabis use are found in never‐tobacco smokers. What Are the Clinical Implications? Patients should be screened for cannabis use and advised to avoid smoking cannabis to reduce their risk of premature cardiovascular disease and cardiac events. Nonstandard Abbreviations and Acronyms BRFSS Behavioral Risk Factor Surveillance System Cannabis use is increasing in the US population.1 From 2002 to 2019, past‐year prevalence of US adult cannabis use increased from 10.4% to 18.0%, whereas daily/almost daily use (300+ days per year) increased from 1.3% to 3.9%. Rising diagnoses of cannabis use disorder suggest that this increase in use is not confined to reporting of use.2, 3 At the same time, perceptions of the harmfulness of cannabis are decreasing. National surveys reported that adult belief in great risk of weekly cannabis use fell from 50% in 2002 to 28.6% in 2019.4 Despite common use, little is known about the risks of cannabis use and, in particular, the cardiovascular disease risks. Cardiovascular‐related death is the leading cause of mortality, and cannabis use could be an important, unappreciated risk factor leading to many preventable deaths.5 There are reasons to believe that cannabis use is associated with atherosclerotic heart disease. Endocannabinoid receptors are ubiquitous throughout the cardiovascular system.6 Tetrahydrocannabinol, the active component of cannabis, has hemodynamic effects and may result in syncope, stroke, and myocardial infarction.7, 8, 9 Smoking, the predominant method of cannabis use,10 may pose additional cardiovascular risks as a result of inhalation of particulate matter.11 Furthermore, studies in rats have demonstrated that secondhand cannabis smoke exposure is associated with endothelial dysfunction, a precursor to cardiovascular disease.11 Past studies on the association between cannabis use and cardiovascular outcomes have been limited by the dearth of adults with frequent cannabis use.7, 12, 13 Moreover, most studies have been in younger populations at low risk for cardiovascular disease, and therefore without sufficient power to detect an association between cannabis use and atherosclerotic heart disease outcomes.7, 12, 14 In addition, tobacco use among adults who use cannabis is common, and small sample sizes prevented analyses on the association of cannabis use with cardiovascular outcomes among nontobacco users. Any independent effects of cannabis and tobacco in the general adult population and effects of cannabis use among those who have never smoked tobacco cigarettes is of interest, because some have questioned whether cannabis has any effect beyond that of being associated with concurrent tobacco use.15, 16, 17 The National Academy of Sciences report on the health effects of cannabis use suggested that “testing the interaction between cannabis and tobacco use and performing stratified analyses to test the association of cannabis use with clinical endpoints in nonusers of tobacco” is necessary to elucidate the effect of cannabis use on cardiovascular health independent of tobacco use.12 We performed these tests and controlled for potential confounders. The Behavioral Risk Factor Surveillance System (BRFSS) is a national cross‐sectional survey performed annually by the Centers for Disease Control and Prevention. Beginning in 2016, an optional cannabis module was included supporting an analysis examining the association of cannabis use with cardiovascular outcomes.18 Although there have been 3 other studies examining the association of cannabis use with cardiovascular events using the BRFSS cannabis module,19, 20, 21 our much larger sample size enabled us to investigate whether cannabis use was associated with atherosclerotic heart disease outcomes among the general adult population, among nontobacco cigarette users, and among younger adults. Methods Study Sample We combined 2016 to 2020 BRFSS data from 27 American states and 2 territories participating in the cannabis module during at least 1 of these years (Table S1). BRFSS is a telephone survey that collects data from a representative sample of US adults on risk factors, chronic conditions, and health care access.18 The BRFSS questions used are summarized in Table S2. Because this study was based on publicly available data and exempt from institutional review board review, informed consent was not obtained. The data and corresponding materials that support the findings of this study are available from the corresponding author upon request. Our sample included those 18 to 74 years old from the BRFSS (N=434 104) who answered the question, “During the past 30 days, on how many days did you use marijuana or hashish?”, excluding (<1%) those who answered “Don't know” or refused to answer. We excluded adults >74 years old because cannabis use is uncommon in this population. Measures We quantified cannabis use as a continuous variable, days of cannabis use in the past 30 days divided by 30. Thus, daily cannabis use is scored 1, and less than daily use scores were proportionately lower. Specifically, daily use was scored as 1=30/30, 15 days per month was scored 0.5=15/30, and nonuse was scored 0=(0/30). Nonusers’ score was 0. Therefore, a 1‐unit change in our cannabis use frequency metric is equivalent to a comparison of 0 days of cannabis use within past 30 days to daily cannabis use. Demographic variables included age, sex, and self‐identified race and ethnicity. Socioeconomic status was represented by educational attainment, categorized as less than high school, high school, some college, or college graduate. Cardiovascular risk factors included tobacco cigarette use (never, former, current), current alcohol consumption (nonuse, nondaily use, daily use), body mass index, diabetes, and physical activity. Nicotine e‐cigarette use was similarly classified as never, former, or current. Outcomes were assessed when respondents were asked, “Has a doctor, nurse, or other health professional ever told you that you had any of the following….?”. Coronary heart disease (CHD) was assessed by: “(Ever told) you had angina or coronary heart disease?” The lifetime occurrence of myocardial infarction (MI): “(Ever told) you had a heart attack, also called a myocardial infarction?” Stroke: “(Ever told) you had a stroke?” Finally, we created composite indicator for cardiovascular disease, which included any CHD, MI, or stroke. Statistical Analysis Complete case‐weighted estimates of demographic and socioeconomic factors, health behaviors, and chronic conditions were calculated using survey strata, primary sampling units clusters, and sampling weights for the 5 years of combined data to obtain nationally representative results for the states using the cannabis module.22P values for bivariate analyses were calculated by the Rao‐Scott corrected χ2 test. We conducted 3 multivariable logistic analyses of the association of lifetime occurrence of CHD, MI, stroke, and the composite of the 3 with cannabis use ([days per month]/30) as a function of demographic and socioeconomic factors, health‐related behaviors, and other chronic conditions, accounting for the complex survey design. The first analysis included the entire sample 18 to 74 years old controlling for tobacco cigarette use and other covariates. The second was conducted among the respondents who had never used tobacco cigarettes. The third was conducted among respondents who had never used tobacco cigarettes or e‐cigarettes. In the first analysis, we tested for an interaction between current cannabis use (any cannabis use frequency between 1 and 30 days) and current tobacco cigarette use to see if there were synergistic effects of cannabis and conventional tobacco use by measuring the coefficient. An interaction was coded as present if frequency of cannabis use was at least 1 day per month, and conventional tobacco use was coded as current. In addition, we examined the variance inflation factors for the cannabis and tobacco use variables to ensure that they were quantifying statistically independent effects. An upper bound of 5 for the variance inflation factor was used for determination of independent effects.23 We performed supplemental analyses restricting the 3 main analyses to younger adults at risk for premature cardiovascular disease, which we defined as men <55 years old and women <65 years old. The difference in age cutoff by sex is due to the protective effect of estrogen.24 We also conducted sensitivity analyses limiting the comparison to daily versus nonusers using the same multivariate model as in the main analysis and using propensity‐score matching (details in Data S1). We used R statistical software version 4.0 (R Core Team, 2020, Vienna, Austria) and survey package to produce complex survey‐adjusted statistics.25, 26 We used the package car to estimate the survey‐adjusted variance inflation factors.27 Results Baseline Characteristics Among the 434 104 respondents 18 to 74 years old who answered the cannabis module, the weighted prevalence of daily cannabis use was 4.0%, nondaily use was 7.1% (median: 5 days per month; interquartile range, 2–14), and nonuse was 88.9%. The most common form of cannabis consumption was smoking (73.8% of current users). The mean age of the respondents was 45.4 years. About half (51.1%) were women, and the majority of the respondents were White (60.2%), whereas 11.6% were Black, 19.3% Hispanic, and 8.9% other race and ethnicity (eg, non‐Hispanic Asian, Native American, Native Hawaiian and Pacific Islander, and those self‐reporting as multiracial) (Table 1). Daily alcohol use and physical activity had a prevalence of 4.3% and 75.0%, respectively. Most of the sample had never used tobacco cigarettes (61.1%). The prevalence of CHD, MI, stroke, and the composite outcome of all 3 were 3.5% (N=20 009), 3.6% (N=20 563), 2.8% (N=14 922), and 7.4% (N=40 759), respectively. The percentage of missing values for each variable was <1% of the total sample size except for race (1.64%) and alcohol use (1.06%).

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Explain simply in 250 words or less the goal of this study, how it was conducted, the results, and whether or not niPGT-A might be a viable method for genetic testing of human embryos.

Fertil Steril. 2024 Jul;122(1):42-51. doi: 10.1016/j.fertnstert.2024.02.030. Epub 2024 Feb 19. A pilot study to investigate the clinically predictive values of copy number variations detected by next-generation sequencing of cell-free deoxyribonucleic acid in spent culture media Gary Nakhuda 1, Sally Rodriguez 2, Sophia Tormasi 2, Catherine Welch 2 Affiliations Expand PMID: 38382698 DOI: 10.1016/j.fertnstert.2024.02.030 Free article Abstract Objective: To investigate the positive predictive value and false positive risk of copy number variations (CNV's) detected in cell free deoxyribonucleic acid (DNA) from spent culture media for nonviable or aneuploid embryos. Design: Diagnostic/prognostic accuracy study. Patient(s): Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF center. Intervention: Embryo selection was performed according to the conventional grading, blinded to noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) results. After clinical outcomes were established, spent culture media samples were analyzed. Main outcome measures: Prognostic accuracy of CNVs according to niPGT-A results to predict nonviability or clinical aneuploidy. Results: One hundred twenty patients completed the study. Interpretations of next-generation sequencing (NGS) profiles were as follows: 7.5% (n = 9) failed quality control; 62.5% (n = 75) no CNVs detected; and 30% (n = 36) abnormal copy number detected. Stratification of abnormal NGS profiles was as follows: 15% (n = 18) whole chromosome and 15% (n = 18) uncertain reproductive potential. An intermediate CNV was evident in 27.8% (n = 5) of the whole chromosome abnormalities. The negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk (RR) for nonviability compared with no detected abnormalities (RR 2.21, 95% CI: 1.66-2.94). No other CNVs were associated with significant differences in the sustained implantation or RRs for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant median absolute pairwise differences between certain subcategories of CNV abnormalities were apparent. Conclusion: Whole chromosome abnormalities were associated with a high positive predictive value and significant RR for nonviability. Embryos associated with other CNVs had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of niPGT-A. Clinical trial registration number: clinicaltrials.gov (NCT04732013). Keywords: Noninvasive PGT-A; PGT-A; cfDNA; niPGT-A; nonselection. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. PubMed Disclaimer Conflict of interest statement Declaration of Interests G.N. is a shareholder in The Fertility Partners (TFP), the parent company of Olive Fertility Centre. S.R. has minority ownership interests in Sequence46. S.T. has minority ownership interests in Sequence46; C.W. has minority ownership interests in Sequence46. Thermo Fisher Scientific is a vendor to Sequence46 but does not have any other affiliations with the authors. Thermo Fisher provided consumables for the NGS methods required for the study but no direct financial support.

[question] Explain simply in 250 words or less the goal of this study, how it was conducted, the results, and whether or not niPGT-A might be a viable method for genetic testing of human embryos. ===================== [text] Fertil Steril. 2024 Jul;122(1):42-51. doi: 10.1016/j.fertnstert.2024.02.030. Epub 2024 Feb 19. A pilot study to investigate the clinically predictive values of copy number variations detected by next-generation sequencing of cell-free deoxyribonucleic acid in spent culture media Gary Nakhuda 1, Sally Rodriguez 2, Sophia Tormasi 2, Catherine Welch 2 Affiliations Expand PMID: 38382698 DOI: 10.1016/j.fertnstert.2024.02.030 Free article Abstract Objective: To investigate the positive predictive value and false positive risk of copy number variations (CNV's) detected in cell free deoxyribonucleic acid (DNA) from spent culture media for nonviable or aneuploid embryos. Design: Diagnostic/prognostic accuracy study. Patient(s): Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF center. Intervention: Embryo selection was performed according to the conventional grading, blinded to noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) results. After clinical outcomes were established, spent culture media samples were analyzed. Main outcome measures: Prognostic accuracy of CNVs according to niPGT-A results to predict nonviability or clinical aneuploidy. Results: One hundred twenty patients completed the study. Interpretations of next-generation sequencing (NGS) profiles were as follows: 7.5% (n = 9) failed quality control; 62.5% (n = 75) no CNVs detected; and 30% (n = 36) abnormal copy number detected. Stratification of abnormal NGS profiles was as follows: 15% (n = 18) whole chromosome and 15% (n = 18) uncertain reproductive potential. An intermediate CNV was evident in 27.8% (n = 5) of the whole chromosome abnormalities. The negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk (RR) for nonviability compared with no detected abnormalities (RR 2.21, 95% CI: 1.66-2.94). No other CNVs were associated with significant differences in the sustained implantation or RRs for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant median absolute pairwise differences between certain subcategories of CNV abnormalities were apparent. Conclusion: Whole chromosome abnormalities were associated with a high positive predictive value and significant RR for nonviability. Embryos associated with other CNVs had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of niPGT-A. Clinical trial registration number: clinicaltrials.gov (NCT04732013). Keywords: Noninvasive PGT-A; PGT-A; cfDNA; niPGT-A; nonselection. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. PubMed Disclaimer Conflict of interest statement Declaration of Interests G.N. is a shareholder in The Fertility Partners (TFP), the parent company of Olive Fertility Centre. S.R. has minority ownership interests in Sequence46. S.T. has minority ownership interests in Sequence46; C.W. has minority ownership interests in Sequence46. Thermo Fisher Scientific is a vendor to Sequence46 but does not have any other affiliations with the authors. Thermo Fisher provided consumables for the NGS methods required for the study but no direct financial support. https://pubmed.ncbi.nlm.nih.gov/38382698/ ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Answer using only the information provided below. Include a quote from the text to support each point.

What are the pros and cons of the Supreme Court having a Code of Conduct?

Ethics and the Supreme Court By its explicit terms, the Code governs only the judges of the lower federal courts. It does not apply to Supreme Court Justices, nor has the Supreme Court formally promulgated its own ethical code. As a result, there is presently no single body of ethical canons with which the nation’s highest court must comply when discharging its judicial duties. The absence of such a body of canons does not mean that Supreme Court Justices are wholly unconstrained by ethical norms and guidelines. Even though the Code does not formally apply to Supreme Court Justices, the Justices “consult the Code of Conduct” and other authorities “to resolve specific ethical issues.” Moreover, although Congress has not enacted legislation mandating the adoption of a Supreme Court code of conduct, several statutes do impose various other ethical requirements upon the Justices. For example, 28 U.S.C. § 455 requires federal judges, including Supreme Court Justices, to recuse themselves from particular cases under specified circumstances, such as when the judge or Justice “has a personal bias or prejudice concerning a party” or “a financial interest in the subject matter in controversy.” Congress has also directed Supreme Court Justices to comply with certain financial disclosure requirements that apply to federal officials generally. In addition, the Court has voluntarily resolved to comply with certain Judicial Conference regulations pertaining to the receipt of gifts by judicial officers, even though those regulations would otherwise not apply to Supreme Court Justices. In response to calls to mandate a code of ethics for the Supreme Court, some Members of the 117th Congress introduced the For the People Act of 2021 (H.R. 1/S. 1), which, among other things, would require “the Judicial Conference [to] issue a code of conduct, which applies to each justice … of the United States.” The Supreme Court Ethics Act (H.R. 4766/S. 2512) would impose the same requirement through standalone legislation. These proposals echo similar bills from past Congresses that would have likewise subjected the Supreme Court to a code of judicial conduct. Legal Considerations for Congress Legislative proposals to impose a code of conduct on the Supreme Court raise an array of legal questions. The first is a question of statutory design: Which institution would Congress charge with formulating the ethical standards to govern the Justices? A legislative proposal introduced in the 115th Congress would have entrusted the Supreme Court itself with the task of “promulgat[ing] a code of ethics” and would have given the Justices substantial (albeit not unbounded) freedom to design the rules that would govern their own conduct. Similarly, a House resolution introduced during the 117th Congress would express “the sense of the House of Representatives that the Justices of the Supreme Court should make themselves subject to the existing and operative ethics guidelines set out in the Code of Conduct for United States Judges, or should promulgate their own code of conduct.” The For the People Act and the Supreme Court Ethics Act, by contrast, would not allow the Court to design its own ethical code; those proposals would instead grant that authority to the Judicial Conference. A related question is whether legislative efforts to require the Supreme Court to abide by a code of judicial conduct would violate the constitutional separation of powers. To ensure that federal judges would decide cases impartially without fear of political retaliation, the Framers of the Constitution purposefully insulated the federal judiciary from political control. Chief Justice John Roberts invoked those ideals in his 2021 Year-End Report on the Federal Judiciary, asserting that the courts “require ample institutional independence” and that “[t]he Judiciary’s power to manage its internal affairs insulates courts from inappropriate political influence and is crucial to preserving public trust in its work as a separate and coequal branch of government.” Some observers have argued that imposing a code of conduct upon the Supreme Court would amount to an unconstitutional legislative usurpation of judicial authority. The House resolution discussed above notes that separation of powers and the independence of the judiciary “may be compromised by extensive legislative or executive interference into that branch’s functions” and would thus avoid imposing any binding requirement on the Court. On the other hand, some commentators emphasize the ways that Congress may validly act with respect to the Supreme Court, for example through its authority to impeach Justices and decide whether Justices are entitled to salary increases. By extension, according to this argument, requiring the Supreme Court to adopt a code of conduct would constitute a permissible exercise of Congress’s authority. Because the Supreme Court possesses the authority to determine the constitutionality of legislative enactments, the Supreme Court itself would appear to have a critical role in determining whether Congress may validly impose a code of ethical conduct upon it. It is difficult to predict whether the Court would uphold the constitutionality of a legislatively mandated code of conduct, as existing judicial precedent offers minimal guidance on how the Court might resolve this constitutional question. For instance, the Supreme Court has never explicitly decided whether the federal statute requiring Supreme Court Justices to recuse themselves from particular cases is an unconstitutional legislative encroachment upon the judiciary, nor has the Court ever directly addressed whether Congress may subject Supreme Court Justices to financial reporting requirements or limitations upon the receipt of gifts. Distinct from this separation-of-powers issue is the question of whether Congress may authorize the Judicial Conference—which is composed almost entirely of judges from the inferior federal courts—to promulgate ethical rules to govern Justices on the High Court. The Constitution explicitly contemplates that the Supreme Court will remain “supreme” over any “inferior” courts that “Congress may from time to time ordain and establish,” such as the federal district and appellate courts. Some observers have therefore suggested that it would be unconstitutional, or at least inappropriate, for the Judicial Conference to make rules for the Supreme Court. As one example, Senior Associate Justice Anthony Kennedy has stated that it would raise a “legal problem” and would be “structurally unprecedented for district and circuit judges to make rules that Supreme Court judges have to follow.” A Supreme Court code of conduct could also raise practical issues to the extent that it would require Justices to disqualify themselves from particular cases. Unlike in the lower courts, where a district or circuit judge from the same court may step in to take a recused judge’s place, neither retired Justices of the Supreme Court nor lower court judges may hear a case in a recused Justice’s stead. The disqualification of a Supreme Court Justice from a particular case could leave the Court with an even number of Justices to decide the case and thus increase the likelihood that the Court would be evenly divided and unable to create binding precedent for future litigants. Conversely, if the other Justices would otherwise be evenly divided, it may be even more critical for a Justice with an appearance of partiality to avoid casting the deciding vote. If one or more Justices refused or failed to comply with a newly created code of conduct, Congress might also encounter difficulties enforcing its tenets. The Constitution forbids Congress from reducing Supreme Court Justices’ salaries or removing them from office except via the extraordinary and blunt remedy of impeachment. Thus, Congress may lack precise tools to induce recalcitrant Justices to behave ethically. Ultimately, the foregoing questions related to a Supreme Court code of conduct may be largely academic. Promulgating an ethical code for the Supreme Court could establish norms for proper judicial behavior that guide the Justices’ actions. Thus, if Congress sought to compel the Supreme Court to comply with a code of judicial conduct, the Justices might simply comply with its mandates without challenging Congress’s constitutional authority to impose them. The Court has often acquiesced to congressional attempts to subject Justices to specific ethical standards. For example, when Congress decided to subject the Justices to financial disclosure requirements, the Justices opted to comply with those provisions rather than challenge their constitutionality in court. Justices have likewise implicitly accepted the validity of 28 U.S.C. § 455, discussed above, and recused themselves pursuant to that statute without questioning whether Congress possesses the constitutional authority to enact a judicial disqualification statute.

Question: What are the pros and cons of the Supreme Court having a Code of Conduct? System Instruction: Answer using only the information provided below. Include a quote from the text to support each point. Context: Ethics and the Supreme Court By its explicit terms, the Code governs only the judges of the lower federal courts. It does not apply to Supreme Court Justices, nor has the Supreme Court formally promulgated its own ethical code. As a result, there is presently no single body of ethical canons with which the nation’s highest court must comply when discharging its judicial duties. The absence of such a body of canons does not mean that Supreme Court Justices are wholly unconstrained by ethical norms and guidelines. Even though the Code does not formally apply to Supreme Court Justices, the Justices “consult the Code of Conduct” and other authorities “to resolve specific ethical issues.” Moreover, although Congress has not enacted legislation mandating the adoption of a Supreme Court code of conduct, several statutes do impose various other ethical requirements upon the Justices. For example, 28 U.S.C. § 455 requires federal judges, including Supreme Court Justices, to recuse themselves from particular cases under specified circumstances, such as when the judge or Justice “has a personal bias or prejudice concerning a party” or “a financial interest in the subject matter in controversy.” Congress has also directed Supreme Court Justices to comply with certain financial disclosure requirements that apply to federal officials generally. In addition, the Court has voluntarily resolved to comply with certain Judicial Conference regulations pertaining to the receipt of gifts by judicial officers, even though those regulations would otherwise not apply to Supreme Court Justices. In response to calls to mandate a code of ethics for the Supreme Court, some Members of the 117th Congress introduced the For the People Act of 2021 (H.R. 1/S. 1), which, among other things, would require “the Judicial Conference [to] issue a code of conduct, which applies to each justice … of the United States.” The Supreme Court Ethics Act (H.R. 4766/S. 2512) would impose the same requirement through standalone legislation. These proposals echo similar bills from past Congresses that would have likewise subjected the Supreme Court to a code of judicial conduct. Legal Considerations for Congress Legislative proposals to impose a code of conduct on the Supreme Court raise an array of legal questions. The first is a question of statutory design: Which institution would Congress charge with formulating the ethical standards to govern the Justices? A legislative proposal introduced in the 115th Congress would have entrusted the Supreme Court itself with the task of “promulgat[ing] a code of ethics” and would have given the Justices substantial (albeit not unbounded) freedom to design the rules that would govern their own conduct. Similarly, a House resolution introduced during the 117th Congress would express “the sense of the House of Representatives that the Justices of the Supreme Court should make themselves subject to the existing and operative ethics guidelines set out in the Code of Conduct for United States Judges, or should promulgate their own code of conduct.” The For the People Act and the Supreme Court Ethics Act, by contrast, would not allow the Court to design its own ethical code; those proposals would instead grant that authority to the Judicial Conference. A related question is whether legislative efforts to require the Supreme Court to abide by a code of judicial conduct would violate the constitutional separation of powers. To ensure that federal judges would decide cases impartially without fear of political retaliation, the Framers of the Constitution purposefully insulated the federal judiciary from political control. Chief Justice John Roberts invoked those ideals in his 2021 Year-End Report on the Federal Judiciary, asserting that the courts “require ample institutional independence” and that “[t]he Judiciary’s power to manage its internal affairs insulates courts from inappropriate political influence and is crucial to preserving public trust in its work as a separate and coequal branch of government.” Some observers have argued that imposing a code of conduct upon the Supreme Court would amount to an unconstitutional legislative usurpation of judicial authority. The House resolution discussed above notes that separation of powers and the independence of the judiciary “may be compromised by extensive legislative or executive interference into that branch’s functions” and would thus avoid imposing any binding requirement on the Court. On the other hand, some commentators emphasize the ways that Congress may validly act with respect to the Supreme Court, for example through its authority to impeach Justices and decide whether Justices are entitled to salary increases. By extension, according to this argument, requiring the Supreme Court to adopt a code of conduct would constitute a permissible exercise of Congress’s authority. Because the Supreme Court possesses the authority to determine the constitutionality of legislative enactments, the Supreme Court itself would appear to have a critical role in determining whether Congress may validly impose a code of ethical conduct upon it. It is difficult to predict whether the Court would uphold the constitutionality of a legislatively mandated code of conduct, as existing judicial precedent offers minimal guidance on how the Court might resolve this constitutional question. For instance, the Supreme Court has never explicitly decided whether the federal statute requiring Supreme Court Justices to recuse themselves from particular cases is an unconstitutional legislative encroachment upon the judiciary, nor has the Court ever directly addressed whether Congress may subject Supreme Court Justices to financial reporting requirements or limitations upon the receipt of gifts. Distinct from this separation-of-powers issue is the question of whether Congress may authorize the Judicial Conference—which is composed almost entirely of judges from the inferior federal courts—to promulgate ethical rules to govern Justices on the High Court. The Constitution explicitly contemplates that the Supreme Court will remain “supreme” over any “inferior” courts that “Congress may from time to time ordain and establish,” such as the federal district and appellate courts. Some observers have therefore suggested that it would be unconstitutional, or at least inappropriate, for the Judicial Conference to make rules for the Supreme Court. As one example, Senior Associate Justice Anthony Kennedy has stated that it would raise a “legal problem” and would be “structurally unprecedented for district and circuit judges to make rules that Supreme Court judges have to follow.” A Supreme Court code of conduct could also raise practical issues to the extent that it would require Justices to disqualify themselves from particular cases. Unlike in the lower courts, where a district or circuit judge from the same court may step in to take a recused judge’s place, neither retired Justices of the Supreme Court nor lower court judges may hear a case in a recused Justice’s stead. The disqualification of a Supreme Court Justice from a particular case could leave the Court with an even number of Justices to decide the case and thus increase the likelihood that the Court would be evenly divided and unable to create binding precedent for future litigants. Conversely, if the other Justices would otherwise be evenly divided, it may be even more critical for a Justice with an appearance of partiality to avoid casting the deciding vote. If one or more Justices refused or failed to comply with a newly created code of conduct, Congress might also encounter difficulties enforcing its tenets. The Constitution forbids Congress from reducing Supreme Court Justices’ salaries or removing them from office except via the extraordinary and blunt remedy of impeachment. Thus, Congress may lack precise tools to induce recalcitrant Justices to behave ethically. Ultimately, the foregoing questions related to a Supreme Court code of conduct may be largely academic. Promulgating an ethical code for the Supreme Court could establish norms for proper judicial behavior that guide the Justices’ actions. Thus, if Congress sought to compel the Supreme Court to comply with a code of judicial conduct, the Justices might simply comply with its mandates without challenging Congress’s constitutional authority to impose them. The Court has often acquiesced to congressional attempts to subject Justices to specific ethical standards. For example, when Congress decided to subject the Justices to financial disclosure requirements, the Justices opted to comply with those provisions rather than challenge their constitutionality in court. Justices have likewise implicitly accepted the validity of 28 U.S.C. § 455, discussed above, and recused themselves pursuant to that statute without questioning whether Congress possesses the constitutional authority to enact a judicial disqualification statute.

You can only answer using from the text provided in the prompt. You can not use any other external resources or prior knowledge. Provide your answer in 5 sentences or less.

What are families' emotional experiences with a child with rare disease before a diagnosis is received?

In the absence of correct diagnosis, emergency units are not in a position to treat the patient appropriately, e.g. headache treated as migraine in a neurological emergency unit, whereas a brain tumour is the underlying cause of the pain. Without a diagnosis, when the patient is a child, the family feels particularly guilty because the child is “acting weird” and is not performing normally in terms of mental and psychomotor development. Any abnormal eating behaviour, which accompanies many rare diseases, is frequently blamed on the mother, causing guilt and insecurity. Incomprehension, depression, isolation and anxiety are an intrinsic part of the everyday life of most parents of a child affected by a rare disease, especially in the pre-diagnosis phase. The whole family of a rare disease patient, whether children or adults, is affected by the disease of the loved one and becomes marginalized: psychologically, socially, culturally and economically vulnerable. In many cases, the birth of a child with a rare disease is a cause for parental splitting. Another crucial moment for rare disease patients is the disclosure of diagnosis: despite the progress made over the last ten years, the diagnosis of a rare disease is all too often poorly communicated. Many patients and their families describe the insensitive and uninformative manner in which diagnosis is given. This problem is common among health care practitioners, who are too often neither organised nor trained in good practice for communicating diagnosis. Up to 50% of patients have suffered from poor or unacceptable conditions of disclosure. In order to avoid face-to-face disclosure, doctors often give the terrible diagnosis by phone, in writing - with or even without explanation – or standing in the corridor of a hospital. Training professionals on appropriate ways of disclosure would avoid this additional and unnecessary pain to already anguished patients and 4 More information about the EurordisCare 2 survey can be found on the following websites: http://www.eurordis.org and http://www.rare-luxembourg2005.org/ “Rare Diseases : Understanding this Public Health Priority” 9/14 Eurordis, November 2005 – www.eurordis.org families. Further schooling in “breaking in bad news” to patients constitutes an important aspect of medical training. A father tells: “When I went to pick up my one year-old daughter in the hospital after I had to leave her for many hours of examinations and testing, I anxiously asked the paediatrician what my baby was suffering from. The doctor hardly looked at me and, rushing down the corridor, shouted: “This baby, you better throw her away, and get another child”. Whatever the conditions of disclosure are, the diagnosis of a rare disease means that life is toppling. In order to help rare disease patients and their families face the future and avoid their world collapsing, psychological support is greatly needed. Every mother and father knows how many worries and hopes are involved in having a child. But what it means to be diagnosed - or having a child diagnosed - with a rare disease cannot be explained.

You can only answer using from the text provided in the prompt. You can not use any other external resources or prior knowledge. Provide your answer in 5 sentences or less. What are families' emotional experiences with a child with rare disease before a diagnosis is received? In the absence of correct diagnosis, emergency units are not in a position to treat the patient appropriately, e.g. headache treated as migraine in a neurological emergency unit, whereas a brain tumour is the underlying cause of the pain. Without a diagnosis, when the patient is a child, the family feels particularly guilty because the child is “acting weird” and is not performing normally in terms of mental and psychomotor development. Any abnormal eating behaviour, which accompanies many rare diseases, is frequently blamed on the mother, causing guilt and insecurity. Incomprehension, depression, isolation and anxiety are an intrinsic part of the everyday life of most parents of a child affected by a rare disease, especially in the pre-diagnosis phase. The whole family of a rare disease patient, whether children or adults, is affected by the disease of the loved one and becomes marginalized: psychologically, socially, culturally and economically vulnerable. In many cases, the birth of a child with a rare disease is a cause for parental splitting. Another crucial moment for rare disease patients is the disclosure of diagnosis: despite the progress made over the last ten years, the diagnosis of a rare disease is all too often poorly communicated. Many patients and their families describe the insensitive and uninformative manner in which diagnosis is given. This problem is common among health care practitioners, who are too often neither organised nor trained in good practice for communicating diagnosis. Up to 50% of patients have suffered from poor or unacceptable conditions of disclosure. In order to avoid face-to-face disclosure, doctors often give the terrible diagnosis by phone, in writing - with or even without explanation – or standing in the corridor of a hospital. Training professionals on appropriate ways of disclosure would avoid this additional and unnecessary pain to already anguished patients and 4 More information about the EurordisCare 2 survey can be found on the following websites: http://www.eurordis.org and http://www.rare-luxembourg2005.org/ “Rare Diseases : Understanding this Public Health Priority” 9/14 Eurordis, November 2005 – www.eurordis.org families. Further schooling in “breaking in bad news” to patients constitutes an important aspect of medical training. A father tells: “When I went to pick up my one year-old daughter in the hospital after I had to leave her for many hours of examinations and testing, I anxiously asked the paediatrician what my baby was suffering from. The doctor hardly looked at me and, rushing down the corridor, shouted: “This baby, you better throw her away, and get another child”. Whatever the conditions of disclosure are, the diagnosis of a rare disease means that life is toppling. In order to help rare disease patients and their families face the future and avoid their world collapsing, psychological support is greatly needed. Every mother and father knows how many worries and hopes are involved in having a child. But what it means to be diagnosed - or having a child diagnosed - with a rare disease cannot be explained.

You must respond using only information provided in the prompt. Explain your reasoning with at least three supporting points.

What are some examples of spillover related to one's level of financial literacy?

A lack of information is sometimes the cause of poor financial decisions. When one party has more information than the other party, economists describe this imbalance as “asymmetric information.” In the market for financial services, where the provider often knows more about the product, there is a potential risk to the consumer and the economy. Financial education is a tool for helping individuals manage and mitigate risk. Individuals who are better financially prepared can avoid unexpected expenses, steer away from frauds and scams, and avoid taking on risks that they do not understand or cannot afford to bear. By improving financial literacy and education, the federal government can play an important role in facilitating a vibrant and efficient marketplace, which in turn empowers individuals to make informed financial decisions. In supporting financial literacy and education, the government can create positive spillovers (or positive externalities) from a more financially literate population. A more informed population tends to be more productive and thus boosts economic activity. A stronger economy can result in more jobs and higher wages for others. Financial education can also help avoid negative spillovers (or negative externalities) from a less financially literate population. A negative externality is an economic 26. GAO, April 2014. 14 Federal Financial Literacy Reform: Coordinating and Improving Financial Literacy Efforts activity that imposes a cost or negative impact on an unrelated third party. These negative externalities cause inefficiencies in the market.27 For example, when a borrower with low financial literacy defaults on an ill-advised loan, the lender will bear some of these costs. On the other hand, friends and family members, the government and others may also bear the cost of that decision. Family members may directly help pay off a loan, or cosign on future loans, increasing their own debt-to-income ratios. Thus, the original two parties to the loan do not bear the entire cost of the transaction. The financial crisis of 2007-2008 demonstrated how individuals and families with limited financial literacy can be among those most dramatically affected by downturns in the economy. Since Treasury’s mission includes a mandate to maintain a strong economy “by promoting the conditions that enable economic growth and stability at home and abroad,”28 it is important to keep in mind the role that individual financial capability has in the prosperity and financial health of the nation. The federal government cannot, and should not, bear the sole responsibility for ensuring the financial capability of individuals and households. Since the creation of the FLEC, it has been clear that federal agencies are not solely, or even predominantly, responsible for providing financial education to Americans. State and local governments, nonprofits and the private sector rightly have interests in promoting better financial decision-making. For example, some employers view financial health similar to physical health and include this as part of their benefits package because of its impact on their bottom line. These non-government entities are able to respond to needs more quickly, develop customized strategies to deliver financial education, and remain engaged and follow up with those served over time. Given the substantial accomplishments and opportunities for improved financial education provided by various stakeholders outside of the federal government, it is appropriate to consider the suitable federal role. Treasury’s outreach to stakeholders has revealed the desire for the federal government to play an overarching leadership and guidance role, rather than trying to directly reach all Americans with financial education lessons. By embracing this role, the federal government can improve the quality and reach of financial education activities by promoting best practices, sharing evidence, creating specific resources where appropriate, and deploying policy solutions to support the U.S. financial education infrastructure. The federal government, then, can be a partner, a source of trusted information and tools, and a leader to the many financial education providers striving to improve financial literacy and capability of their nation. 27. See, for example: Hastings, Justine S., Madrian, Brigitte C. and Skimmyhorn,William L. “Financial Literacy, Financial Education and Economic Outcomes,” Annu Rev Econom. 2013 May 1; 5: 347–373, 2013, available at: https://dx.doi. org/10.1146%2Fannurev-economics-082312-125807; Lusardi, Annamaria and Mitchell, Olivia S. “The Economic Importance of Financial Literacy: Theory and Evidence”, Journal of Economic Literature 2014, 52(1), 5-44, 2014, available at: https://www. aeaweb.org/articles?id=10.1257/jel.52.1.5. 28. U.S. Department of the Treasury, “Role of the Treasury”, webpage, available at: https://home.treasury.gov/about/general-information/ role-of-the-treasury. Section 1: Governance of Federal Financial Literacy and Education Efforts 15 Recommendation Treasury recommends that the primary federal role for financial literacy and education should be to empower financial education providers as opposed to trying to directly reach every American household. This federal role could include developing and implementing policy, encouraging research, and other activities, including conducting financial education programs, and developing educational resources as needed to advance best practices and standards to equip Americans with the skills, knowledge, and tools to confidently make informed financial decisions and improve their financial well-being. The federal government should also consider the impact of the lack of financial literacy on households and the risk to the economy from negative externalities and market failures. Financial literacy and education should be seen as a vehicle to guard against market failures and foster competitive markets. Leadership and Accountability for Federal Financial Literacy and Education The FLEC’s structure and operations have been informal, with the Treasury providing staff support and management, including organizing public meetings, scheduling informal briefings, and managing reports to Congress and the public. While it is clear that there is an important federal role in financial education, the structure of financial education across the federal government has not been conducive to both attaining measurable outcomes and coordinating activities in order to maximize the government’s return on investment. As noted by the OMB Report and the GAO report, financial education activities exist in many different agencies, often without a requirement that they use or build on programs or resources already paid for by taxpayers. Congress created the FLEC with a purpose to coordinate these activities, yet the authorities of the FLEC, as well as its structure, do not provide it with the ability to hold members accountable for coordination, efficiency or outcomes. As GAO noted, “We acknowledge that the governance structure of the Commission presents challenges in addressing resource issues: it relies on the consensus of multiple agencies, has no independent budget, and no legal authority to compel members to act.”29 The FLEC’s lack of clear decision-making processes and defined roles and responsibilities has impeded its ability to effectively carry out its national strategy for financial literacy, and its statutory mandates of both improving financial education, and streamlining and improving federal financial education activities. As a result, the FLEC lacks an effective organizational structure to facilitate goal-setting and decision-making and accountability for outcomes. A more clear and focused leadership structure is needed to guide the work of the FLEC. In addition to structural impediments to coordination, performance and outcome data have not been used systematically to assess the effectiveness of federal activities 29. GAO, April 2014. 16 Federal Financial Literacy Reform: Coordinating and Improving Financial Literacy Efforts and provide a basis to streamline, augment or improve them. Outcomes should reflect the ability of Americans to attain improved financial decision-making as opposed to being activity driven. The GAO has noted that “financial literacy program evaluations are most reliable and effective when they measure the programs’ impact on consumers’ behavior.”30 By adopting measures that member agencies directly impact (performance measures), and indirectly affect (outcome measures), the FLEC will be able to better assess the effectiveness of financial education activities and thus make improvements in the future. Recommendations Treasury recommends the FLEC establish bylaws to set clear expectations for its decision-making and roles, including establishing a six-member Executive Committee comprised of Treasury (chair), CFPB (vice chair), and ED, HUD, DOL and DoD. The Executive Committee will be responsible for crafting, with input from other FLEC members, a shared agenda for action and priorities, and be accountable to report on achievement of that agenda. The agenda would be voted on and approved by a majority of the members.

You must respond using only information provided in the prompt. Explain your reasoning with at least three supporting points. A lack of information is sometimes the cause of poor financial decisions. When one party has more information than the other party, economists describe this imbalance as “asymmetric information.” In the market for financial services, where the provider often knows more about the product, there is a potential risk to the consumer and the economy. Financial education is a tool for helping individuals manage and mitigate risk. Individuals who are better financially prepared can avoid unexpected expenses, steer away from frauds and scams, and avoid taking on risks that they do not understand or cannot afford to bear. By improving financial literacy and education, the federal government can play an important role in facilitating a vibrant and efficient marketplace, which in turn empowers individuals to make informed financial decisions. In supporting financial literacy and education, the government can create positive spillovers (or positive externalities) from a more financially literate population. A more informed population tends to be more productive and thus boosts economic activity. A stronger economy can result in more jobs and higher wages for others. Financial education can also help avoid negative spillovers (or negative externalities) from a less financially literate population. A negative externality is an economic 26. GAO, April 2014. 14 Federal Financial Literacy Reform: Coordinating and Improving Financial Literacy Efforts activity that imposes a cost or negative impact on an unrelated third party. These negative externalities cause inefficiencies in the market.27 For example, when a borrower with low financial literacy defaults on an ill-advised loan, the lender will bear some of these costs. On the other hand, friends and family members, the government and others may also bear the cost of that decision. Family members may directly help pay off a loan, or cosign on future loans, increasing their own debt-to-income ratios. Thus, the original two parties to the loan do not bear the entire cost of the transaction. The financial crisis of 2007-2008 demonstrated how individuals and families with limited financial literacy can be among those most dramatically affected by downturns in the economy. Since Treasury’s mission includes a mandate to maintain a strong economy “by promoting the conditions that enable economic growth and stability at home and abroad,”28 it is important to keep in mind the role that individual financial capability has in the prosperity and financial health of the nation. The federal government cannot, and should not, bear the sole responsibility for ensuring the financial capability of individuals and households. Since the creation of the FLEC, it has been clear that federal agencies are not solely, or even predominantly, responsible for providing financial education to Americans. State and local governments, nonprofits and the private sector rightly have interests in promoting better financial decision-making. For example, some employers view financial health similar to physical health and include this as part of their benefits package because of its impact on their bottom line. These non-government entities are able to respond to needs more quickly, develop customized strategies to deliver financial education, and remain engaged and follow up with those served over time. Given the substantial accomplishments and opportunities for improved financial education provided by various stakeholders outside of the federal government, it is appropriate to consider the suitable federal role. Treasury’s outreach to stakeholders has revealed the desire for the federal government to play an overarching leadership and guidance role, rather than trying to directly reach all Americans with financial education lessons. By embracing this role, the federal government can improve the quality and reach of financial education activities by promoting best practices, sharing evidence, creating specific resources where appropriate, and deploying policy solutions to support the U.S. financial education infrastructure. The federal government, then, can be a partner, a source of trusted information and tools, and a leader to the many financial education providers striving to improve financial literacy and capability of their nation. 27. See, for example: Hastings, Justine S., Madrian, Brigitte C. and Skimmyhorn,William L. “Financial Literacy, Financial Education and Economic Outcomes,” Annu Rev Econom. 2013 May 1; 5: 347–373, 2013, available at: https://dx.doi. org/10.1146%2Fannurev-economics-082312-125807; Lusardi, Annamaria and Mitchell, Olivia S. “The Economic Importance of Financial Literacy: Theory and Evidence”, Journal of Economic Literature 2014, 52(1), 5-44, 2014, available at: https://www. aeaweb.org/articles?id=10.1257/jel.52.1.5. 28. U.S. Department of the Treasury, “Role of the Treasury”, webpage, available at: https://home.treasury.gov/about/general-information/ role-of-the-treasury. Section 1: Governance of Federal Financial Literacy and Education Efforts 15 Recommendation Treasury recommends that the primary federal role for financial literacy and education should be to empower financial education providers as opposed to trying to directly reach every American household. This federal role could include developing and implementing policy, encouraging research, and other activities, including conducting financial education programs, and developing educational resources as needed to advance best practices and standards to equip Americans with the skills, knowledge, and tools to confidently make informed financial decisions and improve their financial well-being. The federal government should also consider the impact of the lack of financial literacy on households and the risk to the economy from negative externalities and market failures. Financial literacy and education should be seen as a vehicle to guard against market failures and foster competitive markets. Leadership and Accountability for Federal Financial Literacy and Education The FLEC’s structure and operations have been informal, with the Treasury providing staff support and management, including organizing public meetings, scheduling informal briefings, and managing reports to Congress and the public. While it is clear that there is an important federal role in financial education, the structure of financial education across the federal government has not been conducive to both attaining measurable outcomes and coordinating activities in order to maximize the government’s return on investment. As noted by the OMB Report and the GAO report, financial education activities exist in many different agencies, often without a requirement that they use or build on programs or resources already paid for by taxpayers. Congress created the FLEC with a purpose to coordinate these activities, yet the authorities of the FLEC, as well as its structure, do not provide it with the ability to hold members accountable for coordination, efficiency or outcomes. As GAO noted, “We acknowledge that the governance structure of the Commission presents challenges in addressing resource issues: it relies on the consensus of multiple agencies, has no independent budget, and no legal authority to compel members to act.”29 The FLEC’s lack of clear decision-making processes and defined roles and responsibilities has impeded its ability to effectively carry out its national strategy for financial literacy, and its statutory mandates of both improving financial education, and streamlining and improving federal financial education activities. As a result, the FLEC lacks an effective organizational structure to facilitate goal-setting and decision-making and accountability for outcomes. A more clear and focused leadership structure is needed to guide the work of the FLEC. In addition to structural impediments to coordination, performance and outcome data have not been used systematically to assess the effectiveness of federal activities 29. GAO, April 2014. 16 Federal Financial Literacy Reform: Coordinating and Improving Financial Literacy Efforts and provide a basis to streamline, augment or improve them. Outcomes should reflect the ability of Americans to attain improved financial decision-making as opposed to being activity driven. The GAO has noted that “financial literacy program evaluations are most reliable and effective when they measure the programs’ impact on consumers’ behavior.”30 By adopting measures that member agencies directly impact (performance measures), and indirectly affect (outcome measures), the FLEC will be able to better assess the effectiveness of financial education activities and thus make improvements in the future. Recommendations Treasury recommends the FLEC establish bylaws to set clear expectations for its decision-making and roles, including establishing a six-member Executive Committee comprised of Treasury (chair), CFPB (vice chair), and ED, HUD, DOL and DoD. The Executive Committee will be responsible for crafting, with input from other FLEC members, a shared agenda for action and priorities, and be accountable to report on achievement of that agenda. The agenda would be voted on and approved by a majority of the members. What are some examples of spillover related to one's level of financial literacy?

Only form your answer with the information provided in the text. Give your answer in a bullet point format.

What are all the price breakdowns the Build Back Better plan provides in its two examples?

As part of the Build Back Better plan, the Biden Administration has proposed several policies to address these long-standing cost pressures. Families with young children will tend to benefit most from the proposed expansion of the Child Tax Credit (CTC), universal preschool, and improvements in the quality of childcare and a reduction in associated out-of-pocket costs. Proposals to lower prescription drug cost through Medicare-negotiated prices, add dental and vision benefits to Medicare, and expand access to home- and community-based care through Medicaid are likely to be more beneficial to households with elderly members. Here, we present two illustrative families as benchmarks for how pieces of Build Back Better aim to help different types of families meet their needs. Specific numbers will vary depending on factors like age, state of residence, and number of children, but these examples try to convey the breadth of the different family policies included in the Administration’s plans. The first example is a family of four with two young children age 4 and 6 living in Indiana. The parents are both 28 years old, have full-time jobs, and together earn $65,000 per year. While the parents are at work, they send the younger child to a high-quality Indiana preschool that costs $9,000 annually.11 Build Back Better would dramatically reduce costs for this Indiana family example. Under Build Back Better’s CTC expansion, the family would receive an extra $2,600 in tax credits.12 Universal preschool would erase the $9,000 they currently spend. All told, Build Back Better would help the Indiana family make ends meet with $11,600 in family cost reductions. The second illustrative family lives in Arizona, with two parents who together earn $85,000 per year and an adult child who lives with them and attends a community college. The family also cares for an elderly parent who needs arthritis medicine, which costs $5,500 per year out-ofpocket, and an eye exam to get a new pair of glasses. Build Back Better would help this Arizona family by making education and health care more affordable. The community college student would be eligible for two years of free community college education, saving the family $2,400 per year.13 Prescription drug reform would cap outof-pocket costs for the elderly parent’s prescription drugs, saving the family another $2,400 per year.14 Finally, new vision benefits under Medicare would pay for the elderly parent’s eye exam and new glasses and lenses, saving $450.15 All told, Build Back Better policies would save this Arizona family $5,250 in annual costs.

System instruction: Only form your answer with the information provided in the text. Give your answer in a bullet point format. Question: What are all the price breakdowns the Build Back Better plan provides in its two examples? Context: As part of the Build Back Better plan, the Biden Administration has proposed several policies to address these long-standing cost pressures. Families with young children will tend to benefit most from the proposed expansion of the Child Tax Credit (CTC), universal preschool, and improvements in the quality of childcare and a reduction in associated out-of-pocket costs. Proposals to lower prescription drug cost through Medicare-negotiated prices, add dental and vision benefits to Medicare, and expand access to home- and community-based care through Medicaid are likely to be more beneficial to households with elderly members. Here, we present two illustrative families as benchmarks for how pieces of Build Back Better aim to help different types of families meet their needs. Specific numbers will vary depending on factors like age, state of residence, and number of children, but these examples try to convey the breadth of the different family policies included in the Administration’s plans. The first example is a family of four with two young children age 4 and 6 living in Indiana. The parents are both 28 years old, have full-time jobs, and together earn $65,000 per year. While the parents are at work, they send the younger child to a high-quality Indiana preschool that costs $9,000 annually.11 Build Back Better would dramatically reduce costs for this Indiana family example. Under Build Back Better’s CTC expansion, the family would receive an extra $2,600 in tax credits.12 Universal preschool would erase the $9,000 they currently spend. All told, Build Back Better would help the Indiana family make ends meet with $11,600 in family cost reductions. The second illustrative family lives in Arizona, with two parents who together earn $85,000 per year and an adult child who lives with them and attends a community college. The family also cares for an elderly parent who needs arthritis medicine, which costs $5,500 per year out-ofpocket, and an eye exam to get a new pair of glasses. Build Back Better would help this Arizona family by making education and health care more affordable. The community college student would be eligible for two years of free community college education, saving the family $2,400 per year.13 Prescription drug reform would cap outof-pocket costs for the elderly parent’s prescription drugs, saving the family another $2,400 per year.14 Finally, new vision benefits under Medicare would pay for the elderly parent’s eye exam and new glasses and lenses, saving $450.15 All told, Build Back Better policies would save this Arizona family $5,250 in annual costs.

Only use the information contained within the provided text to answer the question. Do not use outside sources. Write a full sentence and use a bullet point. Ensure the entire sentence is in italics.

Why is a digital detox so important?

Digital Detox Guide Do you check your email, texts, voicemails, Facebook, or Twitter feed within an hour of waking up or going to sleep? While you’re in line at the store? During dinner with your family? Would you check it at a church while waiting for a funeral to start? Do a little thought experiment with me here. Imagine yourself sitting in a public place, not doing anything, just staring into space. How would you feel? Although many of us spent most of our childhoods daydreaming, adulthood seems to be about trying to keeping our minds from wandering, and trying to stay on task. Rarely do we just let ourselves stare into space these days. Look around: We can’t even stand to wait at a stoplight for 10 seconds without checking our smartphones. Why not? Because it’s uncomfortable for us not to be doing anything. At the very least, it’s boring. More than being boring, however, downtime and daydreaming are threatening to our sense of self. If busyness and multi-tasking and being pressed for time can be equated with significance, success, and productivity then downtime and daydreaming must be signs of insignificance, failure, and inefficiency. And when we feel insignificant and unsuccessful, we also tend to feel guilty for not working, ashamed that we aren’t important enough to be doing something, and anxious about our status. In the lab, these emotions are more painful than the actual physical pain of an electric shock. I’m endlessly fascinated by a series of studies led by Tim Wilson where the research subjects were put alone in a room, with nothing to do. The researchers describe their work: In 11 studies, we found that participants typically did not enjoy spending 6 to 15 minutes in a room by themselves with nothing to do but think, that they enjoyed doing mundane external activities much more, and that many preferred to administer electric shocks to themselves instead of being left alone with their thoughts. Most people seem to prefer to be doing something rather than nothing, even if that something is negative. You read that right: Many people (67 percent of men and 25 percent of women, to be exact) actually gave themselves painful electric shocks instead of just sitting there doing nothing–after they had indicated to the researchers that they would pay money NOT to be shocked again. One guy shocked himself 190 times in 15 minutes. When we can’t tolerate the feelings that come up when we aren’t doing anything, or when we can’t tolerate a lack of stimulation, we feel uncomfortable when we have downtime. As a result, we forfeit our downtime and all its benefits by seeking external stimulation, which is usually readily available in our purse or pocket (rather than an electric shock machine). Instead of just staring out the window on the bus, we read through our Facebook feed. Instead of being alone with our thoughts for a minute, we check our email waiting in line at the grocery store. Instead of enjoying our dinner, we mindlessly shovel food in our mouths while staring at a screen. THE BENEFITS OF UNPLUGGING In the grand scheme of things, digital usage rarely leads to meaning or fulfillment. But unplugging for at least one day per week will make you happier (in addition to giving you hours and hours to do the things that bring meaning to your life). Here’s why: 1. Detoxing from social media and digital information promotes overall wellbeing and mental health. Social media use is associated with narcissism, depression, loneliness, and other negative feelings like anger, envy, misery, and frustration. So, it’s hardly surprising that taking a break for a few days can improve our mood and overall happiness. 2. Your sleep will become more restorative, and sleep improves everything from health and happiness to performance and productivity. Physiologically, you’ll have an easier time sleeping because the low-energy blue light emitted by our tablets and smartphones stimulates chemical messengers in our brains that make us more alert and suppresses others (like melatonin) that help us fall asleep. In addition, you’ll have an easier time sleeping because you won’t be exciting your brain with new or stimulating information right efore bedtime. Social media, messages, and email can easily trigger the release of adrenalin, which makes it nearly impossible to fall asleep quickly. And needless to say, the less time it takes you to fall asleep at night, the more time you’ll have in the morning. 3. Bonus: You’ll feel less lonely and more connected, and feeling connected is the best predictor of happiness that we have. Though we think social media makes us feel more connected to others, ironically, it can also make us feel quite alone. Seeing friends and acquaintances post about how happy they are can actually trigger feelings of misery and loneliness, research shows. The benefits of unplugging from time to time are clearly enormous. But if unplugging isn’t undertaken properly, people often experience withdrawal symptoms, like feelings of agitation, guilt, and a compulsive and distracting desire to check our phones. THE SCIENCE OF CHECKING One survey found that 80% of 18 to 44-year-olds check their smartphones within the first 15 minutes of waking up–and that 89% of younger users, those ages 18- 24, reach for their device within 15 minutes of waking up. Seventy-four percent reach for it immediately after waking up. A quarter of those surveyed could not recall a time during the day that their device was not within reach or in the same room. Another study found that people tend to check their email about every 15 minutes; another found that in 2007 the average knowledge worker opened their email 50 times a day, while using instant messaging 77 times a day—imagine what that might be today, over a decade later, now that smartphones are ubiquitous and given the evidence that we spend more time checking than ever before. So, we check our smartphones constantly. Is that bad? A study of college students at Kent State University found that people who check their phones frequently tend to experience higher levels of distress during their leisure time (when they intend to relax). Similarly, Elizabeth Dunn and Kostadin Kushlev regulated how frequently participants checked their email throughout the day. Those striving to check only three times a day were less tense and less stressed overall. Moreover, checking constantly reduces our productivity. All that checking interrupts us from accomplishing our more important work; with each derailment, it takes us on average about a half hour to get back on track. So why do we check constantly, and first thing in the morning, if it just makes us tense and keeps us from getting our work done? Because it also feels, well…awesome. The Internet and electronic communications engage many of our senses—often simultaneously. All that checking excites our brain, providing the novelty and stimulation it adores. So even though disconnecting from the devices and communications that make us tense and decrease our productivity seems like a logical thing to do, your novelty-and-stimulation-seeking brain won’t want to do it. In fact, it will tell you that you are being more productive when you are online and connected to your messages than when you are disconnected and focusing on something important. This point is worth lingering on: how productive we are does not correlate well with how productive we feel. Multitasking and checking a lot feel productive because our brains are so stimulated when we are doing it. But it isn’t actually productive; one Stanford study showed that while media multitaskers tended to perceive themselves to be performing better, they actually tended to perform worse on every measure the researchers studied. Much of our checking and busyness, to paraphrase Shakespeare, is all sound and fury, no meaning or significance. You can sit all day in front of your computer checking and responding to email but accomplish not one of your priorities. It may feel like a more valuable activity, because it feels more productive. But it is neither. Now that we’ve established the benefits of unplugging and the dangers of checking, here’s how to unplug in a way that will lead to the best weekend EVER. Going unplugged for one day over the weekend will send many people into withdrawal. They will literally experience jitters, anxiety, and discomfort akin to physical pain. If you were in rehab for Opioid addiction, they might give you medication (like Methadone) to ease the pain. Unplugging is like a detox because the symptoms we experience when we stop checking our phones compulsively are uncomfortable; remember, many people would rather receive a painful electric shock than stand the pain of not checking, of not being “productive.” If you need rehab, here’s how to invent your own methadone. The idea is to do something naturally rewarding for your brain to ease the boredom, anxiety, and general twitchiness that tends to descend upon us when we unplug from technology. Unless you are some sort of superhero, you will not be able to cure yourself of your internet/device/email addiction perfectly the first time. So what to do if you’re struggling? 1. Don’t get too emotional about your slip or succumb to selfcriticism. Instead, forgive yourself. Remind yourself that lapses are part of the process, and that feeling guilty or bad about your behavior will not increase your future success. 2. Figure out what the problem is. This may be blazingly obvious, but in order to do better tomorrow, you’ll need to know what is causing your trip-ups. What temptation can you remove? Were you stressed or tired or hungry—and if so, how can you prevent that the next time? 3. Beware the “What the Hell” effect. Say you’ve sworn not to check your email before breakfast, but you’ve been online since your alarm went off…three hours ago. You’re now at risk for what researchers formally call the Abstinence Violation Effect (AVE) and jokingly call the “what the hell effect.” 4. Rededicate yourself to your detox (now, in this instant, not tomorrow). Why do you want to make the changes that you do? How will you benefit? Do a little deep breathing and calm contemplation of your goals. 5. Beware of moral licensing. This is a potential landmine to avoid on your better days: as you notice how well you are doing staying unplugged, don’t let yourself feel so good about the progress you are making that you unleash what researchers call the “licensing effect.”

[DOCUMENT] Digital Detox Guide Do you check your email, texts, voicemails, Facebook, or Twitter feed within an hour of waking up or going to sleep? While you’re in line at the store? During dinner with your family? Would you check it at a church while waiting for a funeral to start? Do a little thought experiment with me here. Imagine yourself sitting in a public place, not doing anything, just staring into space. How would you feel? Although many of us spent most of our childhoods daydreaming, adulthood seems to be about trying to keeping our minds from wandering, and trying to stay on task. Rarely do we just let ourselves stare into space these days. Look around: We can’t even stand to wait at a stoplight for 10 seconds without checking our smartphones. Why not? Because it’s uncomfortable for us not to be doing anything. At the very least, it’s boring. More than being boring, however, downtime and daydreaming are threatening to our sense of self. If busyness and multi-tasking and being pressed for time can be equated with significance, success, and productivity then downtime and daydreaming must be signs of insignificance, failure, and inefficiency. And when we feel insignificant and unsuccessful, we also tend to feel guilty for not working, ashamed that we aren’t important enough to be doing something, and anxious about our status. In the lab, these emotions are more painful than the actual physical pain of an electric shock. I’m endlessly fascinated by a series of studies led by Tim Wilson where the research subjects were put alone in a room, with nothing to do. The researchers describe their work: In 11 studies, we found that participants typically did not enjoy spending 6 to 15 minutes in a room by themselves with nothing to do but think, that they enjoyed doing mundane external activities much more, and that many preferred to administer electric shocks to themselves instead of being left alone with their thoughts. Most people seem to prefer to be doing something rather than nothing, even if that something is negative. You read that right: Many people (67 percent of men and 25 percent of women, to be exact) actually gave themselves painful electric shocks instead of just sitting there doing nothing–after they had indicated to the researchers that they would pay money NOT to be shocked again. One guy shocked himself 190 times in 15 minutes. When we can’t tolerate the feelings that come up when we aren’t doing anything, or when we can’t tolerate a lack of stimulation, we feel uncomfortable when we have downtime. As a result, we forfeit our downtime and all its benefits by seeking external stimulation, which is usually readily available in our purse or pocket (rather than an electric shock machine). Instead of just staring out the window on the bus, we read through our Facebook feed. Instead of being alone with our thoughts for a minute, we check our email waiting in line at the grocery store. Instead of enjoying our dinner, we mindlessly shovel food in our mouths while staring at a screen. THE BENEFITS OF UNPLUGGING In the grand scheme of things, digital usage rarely leads to meaning or fulfillment. But unplugging for at least one day per week will make you happier (in addition to giving you hours and hours to do the things that bring meaning to your life). Here’s why: 1. Detoxing from social media and digital information promotes overall wellbeing and mental health. Social media use is associated with narcissism, depression, loneliness, and other negative feelings like anger, envy, misery, and frustration. So, it’s hardly surprising that taking a break for a few days can improve our mood and overall happiness. 2. Your sleep will become more restorative, and sleep improves everything from health and happiness to performance and productivity. Physiologically, you’ll have an easier time sleeping because the low-energy blue light emitted by our tablets and smartphones stimulates chemical messengers in our brains that make us more alert and suppresses others (like melatonin) that help us fall asleep. In addition, you’ll have an easier time sleeping because you won’t be exciting your brain with new or stimulating information right efore bedtime. Social media, messages, and email can easily trigger the release of adrenalin, which makes it nearly impossible to fall asleep quickly. And needless to say, the less time it takes you to fall asleep at night, the more time you’ll have in the morning. 3. Bonus: You’ll feel less lonely and more connected, and feeling connected is the best predictor of happiness that we have. Though we think social media makes us feel more connected to others, ironically, it can also make us feel quite alone. Seeing friends and acquaintances post about how happy they are can actually trigger feelings of misery and loneliness, research shows. The benefits of unplugging from time to time are clearly enormous. But if unplugging isn’t undertaken properly, people often experience withdrawal symptoms, like feelings of agitation, guilt, and a compulsive and distracting desire to check our phones. THE SCIENCE OF CHECKING One survey found that 80% of 18 to 44-year-olds check their smartphones within the first 15 minutes of waking up–and that 89% of younger users, those ages 18- 24, reach for their device within 15 minutes of waking up. Seventy-four percent reach for it immediately after waking up. A quarter of those surveyed could not recall a time during the day that their device was not within reach or in the same room. Another study found that people tend to check their email about every 15 minutes; another found that in 2007 the average knowledge worker opened their email 50 times a day, while using instant messaging 77 times a day—imagine what that might be today, over a decade later, now that smartphones are ubiquitous and given the evidence that we spend more time checking than ever before. So, we check our smartphones constantly. Is that bad? A study of college students at Kent State University found that people who check their phones frequently tend to experience higher levels of distress during their leisure time (when they intend to relax). Similarly, Elizabeth Dunn and Kostadin Kushlev regulated how frequently participants checked their email throughout the day. Those striving to check only three times a day were less tense and less stressed overall. Moreover, checking constantly reduces our productivity. All that checking interrupts us from accomplishing our more important work; with each derailment, it takes us on average about a half hour to get back on track. So why do we check constantly, and first thing in the morning, if it just makes us tense and keeps us from getting our work done? Because it also feels, well…awesome. The Internet and electronic communications engage many of our senses—often simultaneously. All that checking excites our brain, providing the novelty and stimulation it adores. So even though disconnecting from the devices and communications that make us tense and decrease our productivity seems like a logical thing to do, your novelty-and-stimulation-seeking brain won’t want to do it. In fact, it will tell you that you are being more productive when you are online and connected to your messages than when you are disconnected and focusing on something important. This point is worth lingering on: how productive we are does not correlate well with how productive we feel. Multitasking and checking a lot feel productive because our brains are so stimulated when we are doing it. But it isn’t actually productive; one Stanford study showed that while media multitaskers tended to perceive themselves to be performing better, they actually tended to perform worse on every measure the researchers studied. Much of our checking and busyness, to paraphrase Shakespeare, is all sound and fury, no meaning or significance. You can sit all day in front of your computer checking and responding to email but accomplish not one of your priorities. It may feel like a more valuable activity, because it feels more productive. But it is neither. Now that we’ve established the benefits of unplugging and the dangers of checking, here’s how to unplug in a way that will lead to the best weekend EVER. Going unplugged for one day over the weekend will send many people into withdrawal. They will literally experience jitters, anxiety, and discomfort akin to physical pain. If you were in rehab for Opioid addiction, they might give you medication (like Methadone) to ease the pain. Unplugging is like a detox because the symptoms we experience when we stop checking our phones compulsively are uncomfortable; remember, many people would rather receive a painful electric shock than stand the pain of not checking, of not being “productive.” If you need rehab, here’s how to invent your own methadone. The idea is to do something naturally rewarding for your brain to ease the boredom, anxiety, and general twitchiness that tends to descend upon us when we unplug from technology. Unless you are some sort of superhero, you will not be able to cure yourself of your internet/device/email addiction perfectly the first time. So what to do if you’re struggling? 1. Don’t get too emotional about your slip or succumb to selfcriticism. Instead, forgive yourself. Remind yourself that lapses are part of the process, and that feeling guilty or bad about your behavior will not increase your future success. 2. Figure out what the problem is. This may be blazingly obvious, but in order to do better tomorrow, you’ll need to know what is causing your trip-ups. What temptation can you remove? Were you stressed or tired or hungry—and if so, how can you prevent that the next time? 3. Beware the “What the Hell” effect. Say you’ve sworn not to check your email before breakfast, but you’ve been online since your alarm went off…three hours ago. You’re now at risk for what researchers formally call the Abstinence Violation Effect (AVE) and jokingly call the “what the hell effect.” 4. Rededicate yourself to your detox (now, in this instant, not tomorrow). Why do you want to make the changes that you do? How will you benefit? Do a little deep breathing and calm contemplation of your goals. 5. Beware of moral licensing. This is a potential landmine to avoid on your better days: as you notice how well you are doing staying unplugged, don’t let yourself feel so good about the progress you are making that you unleash what researchers call the “licensing effect.” [QUESTION] Why is a digital detox so important? [TASK INSTRUCTIONS] Only use the information contained within the provided text to answer the question. Do not use outside sources. Write a full sentence and use a bullet point. Ensure the entire sentence is in italics.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

What does author and professor Vauhini Vara have to say about the role of artificial intelligence and literature? Is it a positive perspective? If so, what is her argument?

If artificial intelligence (AI) continues to evolve and becomes capable of producing first-rate literature, will the technology eventually replace human writers? Author, journalist and professor Vauhini Vara addressed the topic during a recent lecture at The Ohio State University’s Columbus campus. Vara spoke on Dec. 7 at Pomerene Hall as part of Ohio State’s “ART-ificial: An Intelligence Co-Lab” project, which is funded by the university’s Artificial Intelligence in the Arts, Humanities and Engineering: Interdisciplinary Collaborations program. The project included a speaker series throughout the spring and autumn semesters that was organized by Elissa Washuta, an associate professor in the Department of English, and Austen Osworth, a lecturer in the School of Creative Writing at the University of British Columbia. “I think we need to talk at length about what these tools are for and what they’re not for and what they can do and what they can’t do and what writing is for,” Washuta said. “A lot of these things are not immediately apparent to students who are learning about writing for the first time in college. They’re having their first encounters with writing studies in college in composition classes.” In her presentation titled “If Computers Can Write, Why Should We?” Vara discussed her relationship with AI as a writing tool. She has written for The New York Times Magazine and Wired, among other publications. She also teaches at Colorado State University as a 2023-24 visiting assistant professor of creative writing. “In the years ahead, scientists are definitely going to work to make AI better and better and better at producing language in the form of literature,” Vara said. “I have no doubt that writers will, like I did, find it interesting and even moving to experiment with AI in their own work.” Vara is the author of “This is Salvaged,” which was named one of the best books of 2023 by Publisher’s Weekly, and “The Immortal King Rao” (2022), which was a finalist for the Pulitzer Prize and was shortlisted for the National Book Critics Circle’s John Leonard Prize and the Dayton Literary Peace Prize. “The Immortal King Rao,” Vara’s debut novel, imagines a future in which those in power deploy AI to remake all aspects of society — criminal justice, education, communication. AI also figured prominently in Vara’s essay “Ghosts,” about her grief over her older sister’s death. She used GPT-3, an AI technology that evolved into ChatGPT, as a writing tool while composing the essay. “Ghosts” went viral upon its publication in The Believer Magazine in 2021. The essay was adapted for an episode of National Public Radio’s “This American Life” and anthologized in “Best American Essays 2022.” “It was more well-received by far than anything else I’d written at that point. And I thought I should feel proud of that to an extent, and I sort of did,” Vara said. “But I was also ambivalent because even though GPT-3 didn’t share the byline with me, I felt like on an artistic level, I could only take partial credit for the piece.” In addition to casting doubt on writers’ originality, AI may replicate the blind spots of the humans who program the technology, Vara said. “The companies behind AI models were training these models by feeding them existing texts … everything from internet message boards to Wikipedia to published books written by human authors,” she said. “The trainings have been used without the consent of the people who’ve written [the published texts]. It was also becoming clear that the models’ outputs … reflected biases, including racial and gender stereotypes.” Though her experiment with AI resulted in a well-received essay, Vara said she has since returned to writing without technological assistance. However, she continues to explore the potential consequences of AI. “I think it’s important to keep in mind that the publishing industry has an incentive to pursue AI-based writing in some form, being that it will almost certainly be cheaper than hiring human writers or paying human writers to produce literature,” she said. “I do hope that as much as that’s all true, we stay aware as readers, as a society, of what it would mean to cede ground to computers entirely in a form that has traditionally been meant for humans to convey what it’s like to be human living in the world to other humans.” Discussions are underway to continue the “ART-ificial: An Intelligence Co-Lab” project next year, Washuta said. “We’re hoping to see if we can continue our work together,” she said. “I think everybody who’s been involved in the planning and who’s presented has been really energized by the conversations that we’ve had.”

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== What does author and professor Vauhini Vara have to say about the role of artificial intelligence and literature? Is it a positive perspective? If so, what is her argument? {passage 0} ========== If artificial intelligence (AI) continues to evolve and becomes capable of producing first-rate literature, will the technology eventually replace human writers? Author, journalist and professor Vauhini Vara addressed the topic during a recent lecture at The Ohio State University’s Columbus campus. Vara spoke on Dec. 7 at Pomerene Hall as part of Ohio State’s “ART-ificial: An Intelligence Co-Lab” project, which is funded by the university’s Artificial Intelligence in the Arts, Humanities and Engineering: Interdisciplinary Collaborations program. The project included a speaker series throughout the spring and autumn semesters that was organized by Elissa Washuta, an associate professor in the Department of English, and Austen Osworth, a lecturer in the School of Creative Writing at the University of British Columbia. “I think we need to talk at length about what these tools are for and what they’re not for and what they can do and what they can’t do and what writing is for,” Washuta said. “A lot of these things are not immediately apparent to students who are learning about writing for the first time in college. They’re having their first encounters with writing studies in college in composition classes.” In her presentation titled “If Computers Can Write, Why Should We?” Vara discussed her relationship with AI as a writing tool. She has written for The New York Times Magazine and Wired, among other publications. She also teaches at Colorado State University as a 2023-24 visiting assistant professor of creative writing. “In the years ahead, scientists are definitely going to work to make AI better and better and better at producing language in the form of literature,” Vara said. “I have no doubt that writers will, like I did, find it interesting and even moving to experiment with AI in their own work.” Vara is the author of “This is Salvaged,” which was named one of the best books of 2023 by Publisher’s Weekly, and “The Immortal King Rao” (2022), which was a finalist for the Pulitzer Prize and was shortlisted for the National Book Critics Circle’s John Leonard Prize and the Dayton Literary Peace Prize. “The Immortal King Rao,” Vara’s debut novel, imagines a future in which those in power deploy AI to remake all aspects of society — criminal justice, education, communication. AI also figured prominently in Vara’s essay “Ghosts,” about her grief over her older sister’s death. She used GPT-3, an AI technology that evolved into ChatGPT, as a writing tool while composing the essay. “Ghosts” went viral upon its publication in The Believer Magazine in 2021. The essay was adapted for an episode of National Public Radio’s “This American Life” and anthologized in “Best American Essays 2022.” “It was more well-received by far than anything else I’d written at that point. And I thought I should feel proud of that to an extent, and I sort of did,” Vara said. “But I was also ambivalent because even though GPT-3 didn’t share the byline with me, I felt like on an artistic level, I could only take partial credit for the piece.” In addition to casting doubt on writers’ originality, AI may replicate the blind spots of the humans who program the technology, Vara said. “The companies behind AI models were training these models by feeding them existing texts … everything from internet message boards to Wikipedia to published books written by human authors,” she said. “The trainings have been used without the consent of the people who’ve written [the published texts]. It was also becoming clear that the models’ outputs … reflected biases, including racial and gender stereotypes.” Though her experiment with AI resulted in a well-received essay, Vara said she has since returned to writing without technological assistance. However, she continues to explore the potential consequences of AI. “I think it’s important to keep in mind that the publishing industry has an incentive to pursue AI-based writing in some form, being that it will almost certainly be cheaper than hiring human writers or paying human writers to produce literature,” she said. “I do hope that as much as that’s all true, we stay aware as readers, as a society, of what it would mean to cede ground to computers entirely in a form that has traditionally been meant for humans to convey what it’s like to be human living in the world to other humans.” Discussions are underway to continue the “ART-ificial: An Intelligence Co-Lab” project next year, Washuta said. “We’re hoping to see if we can continue our work together,” she said. “I think everybody who’s been involved in the planning and who’s presented has been really energized by the conversations that we’ve had.” https://english.osu.edu/alumni-newsletter/winter-2024/role-ai-literature

Answer the following question using only information from the text included below. You must not utilize any other sources or your own reasoning in your response.

What are some examples of informal financial services?

Current debates in microfinance 1 1.1 Subsidised credit provision From the 1950s, governments and international aid donors subsidised credit delivery to small farmers in rural areas of many developing countries. It was assumed that poor people found great difficulty in obtaining adequate volumes of credit and were charged high rates of interest by monopolistic money-lenders. Development finance institutions, such as Agricultural Development Banks, were responsible for the delivery of cheap credit to poor farmers. These institutions attempted to supervise the uses to which loans were put, and repayment schedules were based on the expected income flow from the investment. Returns were often overestimated. For example, calculations would be based on agricultural yields for good years (Adams and Von Pischke, 1992). As a result, loans were often not repaid. The credibility and financial viability of these subsidised credit schemes were further weakened by the use of public money to waive outstanding and overdue loans at election time (Adams and Von Pischke, 1992; Lipton, 1996; Wiggins and Rogaly, 1989). A dependence on the fluctuating whims of governments and donors, together with poor investment decisions and low repayment rates made many of these development finance institutions unable to sustain their lend- ing programmes. Credit provision for poor people was transitory and limited. 1.2 The move to market-based solutions This model of subsidised credit was subjected to steady criticism from the mid-1970s as donors and other resource allocators switched attention from state intervention to market-based solutions. Policy-makers were reminded 5 Microfinance and Poverty Reduction that credit could also be described as debt and that the over-supply of subsidised credit without realistic assessment of people's ability to repay could result in impoverishment for borrowers. At the same time the concept of 'transaction costs', and the notion that full information about borrowers was not available to lenders, were used by the opponents of subsidised credit to justify the high interest-rates charged by money-lenders. Lending money carries with it the risk of non-repayment. In order to know who is creditworthy and who is not, and so reduce this risk, the lender screens potential borrowers. This involves gathering information on the circumstances of individuals, which may not be easy to obtain. Then enforcement costs are incurred to ensure repayment. Through this process risks are reduced, though not eliminated. Where a loan is disbursed on condition that it is used for a particular purpose, supervision costs also arise. Using these tools of analysis it was argued that private money-lenders charged interest rates which were higher than formal bank-rates because of the high costs they faced in terms of risk, particularly when lending without physical collateral. At the same time, it was argued that money-lenders were an efficient source of credit because their greater knowledge of the people to whom they were lending lowered screening costs. Moreover, potential borrowers faced high transaction costs when they sought loans from formal-sector finance institutions. These costs included the time, travel, and paperwork involved in obtaining credit, and were often pro- hibitive for poor clients, especially those most geographically isolated. On the basis of this analysis, a group of economists based at Ohio State University (USA), notably Dale Adams and J D Von Pischke, put forward the view that the provision of credit should be left almost entirely to the private sector. In concentrating on the problems of publicly subsidised credit, these economists ignored the social ties, power relations, and coercion associated with the activities of money-lenders. However, detailed micro-level research has demonstrated the widespread use of interlocked' contracts to force exchange to the disadvantage of poor people (Bhaduri, 1981). Powerful local people, including landlords, employers, and traders, are able to influence the terms of loans made to tenants, workers, and small producers via conditions set in transactions involving land, labour, or crops. For example, traders frequently lend working capital to small farmers on condition that their crops are sold to that trader at a pre-determined price. Similarly, loans are made to workers against the promise of labour to be provided at below the going rate at a set future date (Rogaly, 1996b). Against the background of these debates, recent developments in the design of microfinance schemes have generated an understandably high degree of excitement. This is because innovative features in design have 6 Current debates in microfinance reduced the costs and risks of making loans to poor and isolated people, and made financial services available to people who were previously excluded. 1.3 Making use of social collateral There was little knowledge among formal-sector financial intermediaries of alternatives to physical collateral, until the 1970s, when the Grameen Bank in Bangladesh began using 'peer-group monitoring' to reduce lending risk. The model for credit delivery in the Grameen Bank is as follows: • Groups of five self-select themselves; men's and women's group are kept separate but the members of a single group should have a similar economic background. • Membership is restricted to those with assets worth less than half an acre of land. ⚫ Activities begin with savings of Taka 1 per week per person and these savings remain compulsory throughout membership. • Loans are made to two members at a time and must be repaid in equal instalments over 50 weeks. . Each time a loan is taken the borrower must pay 5 per cent of the loan amount into a group fund. • The group is ultimately responsible for repayment if the individual defaults. • Between five and eight groups form a 'development centre' led by a chair- person and secretary and assisted by a Grameen Bank staff member. • Attendance at weekly group and centre meetings is compulsory. • All transactions are openly conducted at centre meetings. • Each member may purchase a share in the Bank worth Taka 100 Through this system the Grameen Bank has provided credit to over 2 million people in Bangladesh (94 per cent women) with a very low default rate. (Source: Khandker, Khalily and Khan, 1995.) However, peer-group monitoring has not proved necessary to other instit- utions seeking to do away with physical collateral. In Indonesia, government- sponsored banks have successfully used character references and locally- recruited lending agents (Chaves and Gonzales Vega, 1996). The peer-group 7 Microfinance and Poverty Reduction method of Grameen and the individual-user approach of the Bank Rakyat Indonesia (see 1.4) can both be seen as attempts to lower screening costs by using local 'insider' information about the creditworthiness of borrowers. The degree to which Grameen Bank employees themselves implement peer-group monitoring has recently been questioned. It is argued that the reason for the Grameen Bank's high repayment rates is the practice of weekly public meetings at which attendance is compulsory, for the payment of loan instalments and the collection of savings. The meetings reinforce a culture of discipline, routine payments, and staff accountability (Jain, 1996). Another means of improving loan recovery is to insist on regularity of repayment. This is likely to reflect the actual income-flow of the borrower much better than a lump-sum demand at the end of the loan period. Borrowers can make repayments out of their normal income rather than relying on the returns from a new-often untested-mini-business. Neverthe- less, where seasonal agriculture is the main source of income, and borrowers face seasonal hardship, regular repayment scheduling may cause problems. Microfinance specialists have argued that the prospects for scheme's stability are improved by innovations such as social collateral and regular repayments instalments. Indeed, financial sustainability has become an important goal in itself. To achieve sustainability, microfinance institutions, be they NGOs, government agencies, or commercial banks, need to ensure that the costs of providing the service are kept low and are covered by income earned through interest and fees on loans (see Havers, 1996). As microfinance deals, by definition, with small loans, the income generated through interest payments is also small in comparison with administration costs. To generate profits, therefore, it is necessary to increase scale - in other words, to lend to a large number of people (Otero and Rhyne, 1994). 1.4 Savings The regular repayments on loans required by large non-governmental micro- finance institutions in Bangladesh (including BRAC, ASA and Grameen) provide evidence that poor people can save in cash (Rutherford, 1995a). These intensive repayment regimes are very similar to those of rotating savings and credit associations: steady weekly payments, enforced by social collateral, in return for a lump sum. Loans made are, in reality, advances against this stream of savings. By insisting on regular savings, microfinance institutions can screen out some potential defaulters, build up the financial security of individuals, increase funds available for lending, and develop among members a degree of identification with the financial health of the institution. People involved in 8 Current debates in microfinance such schemes may previously have been unable to reach formal-sector banks, complete their procedures, qualify for loans or open savings accounts. 'A savings facility is an extremely valuable service in its own right, which often attracts many more clients than a credit programme, particularly from among the poorest' (Hulme and Mosley, 1996, p147). This evidence that poor people can save in cash has opened up further debate. A distinction is made between schemes in which borrowers must save small and regular amounts in order to obtain loans (termed 'compulsory' saving) and those which offer flexible savings facilities. In the latter case people can deposit and withdraw cash in whatever amounts, and as often, as they wish. This distinction is made especially strongly by Robinson (1995) in her account of the Bank Rakyat Indonesia. The BRI local banking system has about six times as many deposit accounts as loans. On 31 December 1993, BRI's local banking system had $2.1 billion in deposits. These were all voluntary savings. By 31 December 1995, there were 14.5 million savings accounts. Savers with BRI bave access to savings whenever they want. BRI deals with individuals rather than groups. Its savings programme was designed specifically to meet local demand for security, convenience of location, and choice of savings instruments offering different mixtures of liquidity and returns. BRI's local banking system has a loan limit of about $11,000. The idea is that good borrowers should not be forced to leave until they can qualify for the loans provided by ordinary commercial banks. In addition, BRI has a system which gives its borrowers an incentive to repay on time. An additional 25 per cent of the interest rate is added to the monthly payment. This amount is paid back to borrowers at the end of the loan period if they have made every payment in full and on time. There is a corresponding in-built penalty for those who have not. (Source: Robinson, 1994.) Robinson argues that there is an enormous unmet demand for flexible savings services. However, she also warns that managing a savings system of this type is much more complex than running a simple credit programme. Schemes which operate under these 'new' savings and credit technologies are an improvement on the old model of subsidised agricultural and micro- enterprise finance. The story of how they have succeeded in reaching poor people is now the subject of a large literature (for example, Rutherford, 1995b; Hulme and Mosley, 1996; Mansell-Carstens, 1995). That many more poor people can now obtain financial services is a major achievement of these 9 Microfinance and Poverty Reduction schemes. However, the questions of which poor people have been reached, and of whether poverty has been reduced, still remain. 1.5 Can microfinance interventions reduce poverty? If poverty is understood as low levels of annual income per household, reducing poverty is about raising average income levels. If a particular level of annual income per head is used as a poverty line, poverty reduction could be measured by counting the number or proportion of people who cross that line-who are promoted out of poverty. Providers of financial services who aim to enable people to cross such a poverty line have focused on credit, in particular credit for small enterprises, including agricultural production. However, attention to annual income can obscure fluctuations in that income during any given year. Poverty can also be understood as vulner- ability to downward fluctuations in income. Such fluctuations can be relat- ively predictable, such as the seasonal decline in employment for agricultural workers, or a shortage of income and trading opportunities in the dry season or before harvest. Alternatively, fluctuations in income may result from unexpected shocks such as crop failure, illness, funeral expenses or loss of an asset such as livestock through theft or death, or a natural disaster such as a cyclone (Montgomery, 1996). Vulnerability can be heightened by the lack of saleable or pawnable assets and by debt obligations. Interventions which reduce such vulnerability and protect livelihoods also reduce poverty. 1.5.1 Poverty as powerlessness A further dimension of poverty which is often the focus of NGO interventions is powerlessness, whether in an absolute sense or in relation to others. Economic inequality between and within households is likely to be associated with concentrations of political and social power. Inequality can increase whenever better-off people are able to improve their incomes faster than others. Even if the absolute level of material well-being of the worst-off people does not change, relative poverty (Beck, 1994) may increase, and with it a sense of powerlessness among very poor people. Power relations are partly determined by norms of expected behaviour. Neither the relations nor the norms are static; they are contested and change over time. Powerlessness can be experienced in a variety of situations: within the household, as a result of differences in gender and age; and within the community, between socio-economic groups, as a result of caste, ethnicity, and wealth. Defining poverty in terms of power relations implies that assessment of the impact of microfinance interventions should focus on their 10 Current debates in microfinance influence on social relations and the circumstances which reproduce them. Even in a similar geographical and historical context, it is important to disting- uish between the ways in which specific groups of poor people (women and men, landed and landless, particular ethnic groups) are able to benefit from financial services or are excluded from doing so. 1.5.2 Credit for micro-enterprises While there are methodological difficulties involved in measuring increases in incomes brought about by the provision of credit (see further discussion in Chapter 5), studies have demonstrated that the availability of credit for micro- enterprises can have positive effects. A recent survey collected data from government, NGOs, and banks involved in providing financial services for poor people. Twelve programmes were selected from seven countries (six of these are included in Table 1, Annex 1). Households which had received credit were compared with households which had not. The results demon- strated that credit provision can enable household incomes to rise. However, taking the analysis further, Hulme and Mosley demonstrated that the better-off the borrower, the greater the increase in income from a micro- enterprise loan. Borrowers who already have assets and skills are able to make better use of credit. The poorest are less able to take risks or use credit to increase their income. Indeed, some of the poorest borrowers interviewed became worse off as a result of micro-enterprise credit, which exposed these vulnerable people to high risks. For them, business failure was more likely to provoke a livelihood crisis than it was for borrowers with a more secure asset base. Specific crises included bankruptcy, forced seizure of assets, and unofficial pledging of assets to other members of a borrowing group. There have even been reports of suicide following peer-group pressure to repay failed loans (Hulme and Mosley, 1996, pp120-122). A much smaller survey comparing micro-enterprise programmes in El Salvador and Vanuatu found that the development of successful enterprises and the improvement of the incomes of very poor people were conflicting rather than complementary objectives. By selecting those most likely to be successful for credit and training, the programmes inevitably moved away from working with the poorest people (Tomlinson, 1995). Reviews of Oxfam's experiences with income-generating projects for women raised serious questions about the profitability of such activities. Full input costings, which would have revealed many income-generating projects as loss- making, were not carried out. Omissions included depreciation on capital, the opportunity cost of labour (the earnings participants could have had through spending the time on other activities), and subsidisation of income- 11 Microfinance and Poverty Reduction generating projects with income from other sources. Market research and training in other business skills had often been inadequate (Piza Lopez and March, 1990; Mukhopadhyay and March, 1992). 1.5.3 Reaching the poorest Whether income promotion is based on loans for individual micro-enterprises or on group-based income generation projects, its appropriateness as a strategy for poverty reduction in the case of the poorest people is questionable. Other evidence suggests that self-selected groups for peer-monitoring have not been inclusive of the poorest people (Montgomery, 1995). People select those with whom they want to form a group on the basis of their own know- ledge of the likelihood that these people will make timely payment of loan and savings instalments: X will only have Y in her group if she believes Y is capable of making regular repayments and has much to lose from the social ostracism associated with default. This system might well be expected to lead to the exclusion of the poorest (Montgomery, op. cit.). Even the low asset and land-holding ceiling which the big microfinance institutions in Bangladesh have successfully used to target loans away from better-off people has not necessarily meant that the poorest, who are often landless, are included (Osmani, 1989). So while the innovations referred to earlier appear to have made loans more available to poor people, there is still debate over the design of appro- priate financial services for the poorest. Hulme and Mosley's study strongly suggests that providing credit for micro-enterprises is unlikely to help the poorest people to increase their incomes. However, detailed research with users has found that some design features of savings and credit schemes are able to meet the needs of very poor people. For example, it was found that easy access to savings and the provision of emergency loans by SANASA (see 3.4.2) enabled poor people to cope better with seasonal income fluctuations (Montgomery, 1996). Microfinance specialists increasingly, therefore, view improvements in economic security income protection rather than promotion (Dreze and Sen, 1989) as the first step in poverty reduction. ...from the perspective of poverty reduction, access to reliable, monetized savings facilities can help the poor smooth consumption over periods of cyclical or unexpected crises, thus greatly improving their economic security.' It is only when people have some economic security that 'access to credit can help them move out of poverty by improving the productivity of their enterprises or creating new sources of livelihood' (Bennet and Cuevas, 1996, authors' emphasis). Current debates in microfinance 1.6 Financial interventions and social change Interventions have an impact on social relations partly through their econ- omic effects. In many instances implementors of credit schemes have claimed that the work will lead to progressive social change, for example by empow- ering women and changing gender relations in the household and in the community (Ackerly, 1995). In five out of the six schemes summarised in Table 1 (Annex 1), over half of the borrowers were women. Much of the work that has been done in assessing the impact of credit programmes on women has been in Bangladesh. One approach was to look at the control women retained over loans extended to them by four different credit programmes: the Grameen Bank, BRAC, a large government scheme (the Rural Poor Programme RD-12), and a small NGO (Thangemara Mahila Senbuj Sengstha) (Goetz and Sen Gupta, 1996). Results suggested that women retained significant control over the use to which the loan was put in 37 per cent of cases; 63 per cent fell into the categories of partial, limited or no control over loan use. Goetz and Sen Gupta found single, divorced, and widowed women more likely to retain control than others. Control was also retained more often when loan sizes were small and when loan use was based on activities which did not challenge notions of appropriate work for women and men. The question of whether women were empowered is not answered: even when they did not control loans, they may have used the fact that the loan had been disbursed to them as women to increase their status and strengthen their position in the household. However, in some cases women reported an increase in domestic violence because of disputes over cash for repayment instalments. A second major piece of research has assessed the effect of Grameen and BRAC programmes on eight indicators of women's empowerment: mobility, economic security, ability to make small purchases, ability to make larger purchases, involvement in major household decisions, relative freedom from domination by the family, political and legal awareness, and participation in public protests and political campaigning (Hashemi et al, 1996). The study concludes that, on balance, access to credit has enabled women to negotiate within the household to improve their position. However, unlike the Goetz and Sen Gupta study, which is based on 275 detailed loan-use histories, Hashemi et al attempted to compare villages where Grameen or BRAC were present with villages where they were not. Because of difficulties inherent in finding perfect control villages (which the authors acknowledge), the conclusions of the study do not signify the end of the debate. It has also been argued that focusing on women is much more to do with financial objectives than with the aim of empowerment. According to 13 Microfinance and Poverty Reduction Rutherford (1995b) the real reasons for targeting women in Bangladesh are that they are seen as accessible (being at home during working hours); more likely to repay on time; more pliable and patient than men; and cheaper to service (as mainly female staff can be hired). Thus the process of loan supervision and recovery may be deliberately internalised inside the household (Goetz and Sen Gupta, op. cit.). Goetz and Sen Gupta do not use this as an argument against the provision of finance for women in Bangladesh, but rather suggest that to avoid aggravating gender- based conflict, loans should be given to men directly as well as to women and, at the same time, that efforts should be made to change men's attitudes to women's worth. 1.7 Treading carefully in microfinance interventions This brief summary of evidence and argument suggests that microfinance interventions may increase incomes, contribute to individual and household livelihood security, and change social relations for the better. But that they can not always be assumed to be doing so. Financial services are not always the most appropriate intervention. The poorest, in particular, often face pressing needs in terms of primary health care, education, and employment opportunities. Lipton has recently argued for anti-poverty resources to be allocated across sectors on the basis that a concentration on a single interven- tion mechanism, say credit, is much less effective in poverty reduction than simultaneous credit, primary health, and education work, even if this entails narrowing geographical focus (op. cit.). The particular combinations which will be most effective will depend on the nature of poverty in a specific context. Although microfinance provision appears to be evolving towards greater sustainability, relevance, and usefulness, there are few certainties and the search for better practice continues. Decisions on whether and how to intervene in local financial markets should not be taken without prior knowledge of the working of those markets. If the intervention is intended to reduce poverty, it is especially important to know the degree to which poor people use existing services and on what terms. Only then can an intervening agency or bank make an informed decision on whether their work is likely to augment or displace existing 'pro-poor' financial services. If the terms of informal financial trans- actions are likely to work against the interests of poor people (cases in which the stereotype of 'the wicked money-lender' corresponds to reality) the inter- vention may attempt to compete with and possibly replace part of the informal system. However, making such an informed assessment is not straight- forward, as one study of the power relations between informal financial 14 Current debates in microfinance service providers and agricultural producers in Tamil Nadu demonstrated. Grain merchants based in the market town of Dindigul were found to dictate the terms of product sale when lending working capital to very small-scale farmers, but to be much the weaker party when lending to larger-scale farmers (Rogaly, 1985). The structure of a credit market can change, partly under the influence of outside intervention. Rutherford has studied the changing market in financial services for poor people in Bangladesh. Competition between NGOs is leading to users being less subservient to NGO staff and protesting about unpopular financial obligations, such as the 5 per cent deducted from loans by Grameen for a 'group fund'. Private individuals have set up offices imitating the Grameen style but charging higher interest rates on loans than the big NGOS, and also offering higher rates on savings deposits. Private urban finance companies have expanded. Despite the tendency for NGOs to become more like banks, other formal-sector lenders are still reluctant to lend to poor people (see also McGregor, 1994). The expansion of NGO credit in Bangladesh has been made possible by the flood of donor money to that country. One study of BRAC showed that loan disbursal and recovery had become more important than group forma- tion (Montgomery, 1996). In 1992, Grameen Bank and BRAC employees were found to be offering 'immediate loans' to women in villages where smaller NGOs had been attempting longer-term group-based finance (Ebdon, 1995). Ebdon attributed this behaviour to fairly strict targets for loan disbursal in the case of BRAC, and in both cases to an imperative for job security for staff and a desire on the part of the organisations to expand their influence and strengthen their reputations (p52). This anxiety to increase the number of users can undercut the very basis of the new model: the creation of sustainable financial institutions. Studies of credit schemes have consistently demonstrated that unless borrowers and savers believed they would benefit from the long-term survival of the institution, and have a sense of ownership, repayment rates would decline (Rogaly, 1991; Copestake, 1996a). The sense of ownership is weakened by attempts by large microfinance institutions in Bangladesh to claim territory by encroachment. In India, in the absence of equivalent flows of external finance, thrift and credit co-operatives based much more on borrowers' requirements have emerged (Rutherford, 1995b, p136). An understanding of the way in which the institutions themselves change and respond to incentives is therefore necessary for the design of relevant anti-poverty interventions, including financial services. 15 2 Informal financial services 2.1 Introduction In recent years research into informal financial services and systems has significantly deepened understanding of the way they operate and their strengths and weaknesses. A simplistic belief that local money-lenders charged extortionate interest rates lay behind the provision of subsidised finance in the past. More thorough investigation has highlighted a range of savings, credit, and insurance facilities accessible to poor people. The appar- ently usurious interest charges reportedly made by private money-lenders may be explainable in terms of transaction costs, lack of information, and high risk. Informal financial services may be well-equipped, because of local 'insider' knowledge, and lower overheads, to respond to the requirements of poor people; they may also be exploitative. This chapter starts with a brief overview of the types of informal services that have been found to exist in a wide variety of countries and social contexts. Some of the broad characteristics of these services are identified, and lessons drawn for the design of NGO or semi-formal systems. In describ- ing informal financial services it is useful to distinguish between those which are owned by their users and those which are offered by an individual, usually on a profit-making basis. The distinction can be a helpful one in analysing the ways in which financial services enable or exploit poor people. NGOs considering microfinance interventions need first to find out what informal financial services are available, and how they operate. Such services are capable of supporting poor people's livelihoods as well as perpetuating 1 This chapter draws heavily on a background paper commissioned for the purposes of this book: A Critical Typology of Financial Services for the Poor, Stuart Rutherford, November 1996. Examples are drawn from Rutherford's own experience unless otherwise stated. 16 Informal financial services structures which undermine them. It is necessary, therefore, to understand under what circumstances and to what degree these services are enabling or exploitative for poor people. On the whole, user-owned services are likely to be more enabling than services provided for profit. Investigating the scope and nature of existing services is an essential pre- liminary before considering whether an intervention is necessary. However, NGOs themselves may not have the right skills to become direct providers of financial services. Furthermore, financial services are needed by poor people on a permanent basis to enable them to plan and manage their finances; NGO programmes which might be here today and gone tomorrow may be an inap- propriate means through which to provide them. Therefore NGOs should seriously consider whether direct intervention is in fact the best response for them to make. The chapter closes by discussing alternative strategies NGOs might employ. 2.2 User-owned informal financial services Systems which facilitate financial transactions and are owned by their users are many and varied, and range from simple reciprocal arrangements between neighbours, savings clubs and rotating savings and credit associa- tions (ROSCAS), to forms of insurance, building societies, and systems of co- operative business finance. An example of each of these types is described below. All of these systems can be found in a variety of country settings. Rotating savings and credit associations (ROSCAS) in particular, are an extremely common phenomenon. They exist in almost every country (for example, 'partners' in Jamaica and Britain, bui in Vietnam, and njangi in Cameroon). (See Bouman, 1995; Ardener and Burman, 1995 for detailed and extensive surveys of ROSCA operations in a range of settings.) The principle is very simple: a number of people agree to save a fixed amount of money at regular intervals; at each meeting, for example weekly, each member contri- butes an agreed amount, resulting in a single lump sum becoming available, which is then allocated to one of the members. There are three basic varia- tions in the way in which this lump sum or 'prize' is allocated. First, it can be allocated on the basis of strict rotation between members of the group; second, on the basis of a lottery of members; third, it may be auctioned to the member who is willing to accept the biggest discount. The group will usually meet (but does not always need to) and undertake this transaction on as many occasions as there are members of the group, thus ensuring that each member gets the 'prize' once. The ROSCA demonstrates the basic principle of financial intermediation: collecting many small savings from many people, turning this into a lump sum for one person, and repeating this procedure over time. 17 Microfinance and Poverty Reduction ROSCA finance is used for many purposes. Some ROSCAS operate to enable an asset to be purchased, such as a rickshaw or fishing equipment for each member, and may have been set up specifically for the purpose. 'Merry- go-rounds', as ROSCAS are called among Kikuyu women in Kenya, are sometimes used by women as a means of accumulating enough money to buy new household utensils or clothes. The technology of the ROSCA is not unique to poor communities but is also used by salaried professionals to purchase major consumption items or assets such as refrigerators or cars. A further example of a user-owned device is the insurance fund which makes pay-outs conditional on certain circumstances occurring. These are int- ended to cover large expenses such as those connected with marriage or death. 2.2.1 Some examples of user-owned financial services Neighbourhood reciprocity in Southern India Reciprocal lending may be extended to involve several or even all the members of a community. Among Moslems in Kerala State in southern India kuri kalyanam are invitations to a feast to which the guest is expected to bring a cash gift. When the host in his turn is invited to a feast by one of the guests he is expected to return double the amount (less if he is perceived as poor). In Vietnam one kind of hui (a generic name for various financial devices) involves a similar pooling of resources for one person on one occasion to be reciprocated later by others, at different times. Rickshaw ROSCAS in Bangladesh Very poor men driven by poverty from their home villages to the Bangladesh capital, Dhaka, often earn a living there by driving bired rickshaws. In the last ten years they have begun to run ROSCAS. A group of drivers forms, and each driver saves a set amount from his daily takings. When the fund is large enough (this usually takes about 15 days) a rickshaw is bought and distributed by lottery to one of the members. In between prizes' the cash is held by a trustworthy outsider, usually a local shopkeeper from whom the members buy their tea or cigarettes. In a further adaptation, those who have already received their rickshaw double their daily contribution. This progressively reduces the time-gap between prizes, and is seen as a fair way of rewarding those members who win the lottery late in the cycle, because their gross contribution is smaller than earlier winners. The extra payment made by the winners is roughly equivalent to what they save by no longer having to hire a rickshaw. 18 An accumulating savings club in Mexico Informal financial services In towns and villages in Mexico neighbours place frequent but irregular savings with trusted shopkeepers. Just before Christmas, the cash is returned to the saver. No interest is paid, but the saver has a lump sum to spend, and the shopkeeper has had the use of the money over the year and can now look forward to a good sales season. Building societies for the middle classes in Bangladesh In a lower-middle-class area of Dhaka, 165 employees in the Public Works Department belong to their own building society' which was started over 16 years ago. Each saves 200 taka ($5) a month out of his wages. As the cash accumulates it is lent out to members, who buy land and building materials. Interest rates are high and interest on the out- standing balance has to be paid each month, to encourage modest loans and rapid repayment. But loan sizes are generous and such workers would have few or no alternative sources for loans of this kind. Popular insurance: funeral funds (iddir) in Ethiopia Originally burial societies, iddir have extended to provide a wide range of insurance services in urban Ethiopia. Aredo (1993), study- ing these in Addis Ababa, estimated that 50 per cent of urban house- holds were members of some kind of iddir. Groups of people come together on the basis of location, occupation, friendship or family ties. Each iddir sets its own rules and regulations but usually pays out for funeral expenses or financial assistance to families of the deceased, and sometimes to cover other costs, such as medical expenses and losses due to fire or theft. 2.3 Informal financial services for profit Those offering informal financial services for profit fall into two groups: deposit takers (often also called money-guards) and lenders. What is most interesting about the situation of deposit takers is that, as in the Nigerian example below, savers usually pay for the service by obtaining a negative interest rate on their funds. This demonstrates the pressing need that people have for places to put their savings which are safe and secure not only from physical risks such as theft, fire or flood, but also from the demands of their family. For women, in particular, the ability to save small amounts in places to which their husbands and families cannot gain access (although they might know about them) has been shown to be particularly important. It may enable them to meet obligations in the family or household, such as the payment of children's school fees, for which they have particular responsibility. 19 Microfinance and Poverty Reduction Forms of lending also operate in a variety of ways, such as money-lenders; pawnbrokers, who take collateral in the form of physical assets; and forms of trade credit and hire purchase. The term 'money-lender' can cause confusion because it conjures up the image of a class of people whose main source of income is usury. In reality, many small farmers, for example, obtain credit from employers, landlords, traders, relatives, and other people who combine a number of economic activities. In some places money-lenders may be a more professionalised class, such as the Tamilians' in Cochin described below, but even in this case it is not necessarily their main source of income. Lending money can be exploitative of, as well as enabling for, poor people. People facing seasonal shortages may have only one source of credit, for example, an employer. The employer may agree to provide a loan, but only if the borrower promises to work when required at below the going wage-rate. As described below for Indonesia, crop traders may provide producers with seasonal credit on the understanding that the crop is sold through the same trader at low post-harvest prices. Tied credit of this type, whether in cash or kind, may be the only means of survival for poor people. But arrangements such as these can maintain and even exacerbate inequalities in power and position. In contrast, user-owned devices are likely to be more supportive and enabling, because the profits made are pooled, and shared or fed back into the system, and ownership and control of the funds are in the hands of the users. Such devices are unlikely to be exploitative of those involved, although they may widen inequalities between users and non-users. The comparison with services for profit is clear. However, loans from private lenders after harvest may enable small traders to make the most of the increased liquidity in the local economy. This emphasises the need for interveners to understand the workings of real markets and to question untested assumptions. It is essential to find out for which groups of poor people-women, men, landless labourers, subsistence farmers, migrant workers and under what circumstances these arrange- ments may be no more than a means of survival, while supporting wealth creation for others. 2.3.1 Some examples of informal financial services provided for profit Deposit takers: a mobile alajo in Nigeria One consequence of Nigeria's current political difficulties is a drop in public confidence in formal banks, according to Gemini News. This has allowed an old tradition to flourish again- alajos, or peripatetic deposit takers. Idowu Alakpere uses a bicycle to go 20 Informal financial services door-to-door round the outer suburb of Lagos where he lives. He has 500 customers who each save about 10 or 15 naira with him (about 50 to 75 cents US) at each daily visit. Customers withdraw money whenever they like, and Idowu charges them one day's savings per month, which he deducts from the withdrawal. Since deposits are made evenly over the month, the negative interest rate for one-month deposits is 1/15, or 6.6 per cent a month, an Annual Percentage Rate (APR) of 80 per cent. Some alajos, including Idowu, store the cash in a reliable bank, others use it to make loans. The Gemini News reporter was told by many local people that they trusted these alajos more than banks. When it was pointed out that some alajos are dishonest, they retorted that so are many banks. Professional money-lenders in Cochin, India 'Tamilians' provide a money-lending service to poor slum dwellers on a daily basis. They have set terms, which are well-known all over Cochin. For each 100 rupees lent, 3 rupees are deducted at source as a fee. Thereafter, 12.50 rupees per week must be repaid for ten weeks. This works out at an APR of 300 per cent (28 rupees paid on an average size loan of 48.50 rupees [97/2) for 10/52 of a year). Most non-poor observers regard this rate as outrageously exploitative. However, poor users of the service tend to take a favourable view of it. The 'Tamilians' do not needlessly harass their clients over repay- ment but take an 'understanding' view which includes a willingness to accept loan losses. These money-lenders know their clients well and (out of self-interest) will not lend more than they think the client can repay out of normal income over the next ten weeks. Lending against collateral: pawnbrokers in Western India Residents of the slums of Vijayawada use their local pawnbroker when they need money quickly. He is reliably available at his gold- smithing shop and he charges 3 per cent a month for loans pledged against gold, 5 per cent for silver and 9 per cent for brass. The inclu- sion of brass means that even the very poor can get a small advance by pawning kitchen pots and pans. He lends up to two-thirds the value of the pawn. He gives a receipt, and because the borrower can be sure of getting her pawn back when she repays the loan, she can risk pawning objects of sentimental value. Unlike those who lend without collateral the broker does not need to know his clients well: the unambiguous collateral provided by the pawn means that the broker can lend to more or less anyone at any time. 21 Microfinance and Poverty Reduction Advance crop sales in Indonesia A practice common in many countries is known as ijon in some areas of Indonesia. Farmers often need cash to get them through the 'bungry' season when their main crop is in the ground and there is not much else to do except sit and wait. They are forced to make an advance sale of the crop, usually to a grain buyer or his agent. Ijon transactions of this sort, if seen as loans, show an interest rate of anything from 10 to 40 per cent a month. (Source: Bouman and Moll in Adams and Fitchett, 1992.) Two examples of trade credit In many markets it is common to see poor people squatting on the ground with a small amount of fertiliser spread out on a mat. The fertiliser doesn't necessarily belong to the man or woman (or, often, child). Lacking capital themselves to buy stock, such people obtain the fertiliser on credit from a nearby shop. At the close of the market they return the money from sales and any balance of the stock to the shopkeeper, retaining a small proportion of the money. The system allows people to trade (safely if not profitably) without capital, and gives the shopkeeper a cheap extra outlet. The dadon credit system used to finance prawn cultivation in Bangladesh is an example of a trading system in which credit is passed on through a chain of intermediaries between the prawn farmer and exporters to Europe. The prawn market is a highly com- petitive business in which everyone in the chain is short of capital. The 'commission agent' at the port buys prawns on behalf of the exporters in the capital. To ensure their share of the market they provide credit early in the season which finds its way through a number of intermediaries before reaching the hands of the farmer. The intermediaries are 'depot' owners, then farias', or merchants, and finally local traders, who in turn lend to the farmers. In accepting the credit the farmer commits himself to selling exclusively to this particular trader. 2.4 Turning the informal into the formal In some countries such informal systems have evolved into formal systems which have had a major impact on their users. In the UK, for example, 'mutual' or friendly societies which began as small thrift groups in the nineteenth century turned into building societies in the first half of the twentieth, and have been the main source of housing finance for 50 years. Informal financial services There are further examples of such informal systems becoming increas- ingly formalised. Aredo (1993) reports that the iddir in Addis Ababa run by the Ethiopia Teachers' Association is of the scale of a medium-size insurance business. In Cameroon some of the traditional ROSCAS known as njangi have evolved into small banks offering finance for small businesses which have difficulty using formal banks (Haggblade, 1978). ROSCAS may thus be a transitional phenomenon. Chit funds in India are a formalised version of a ROSCA, for which govern- ment legislation exists. In contrast to the ROSCA, members of the chit fund do not normally know each other and are merely customers of the chit companies. The company advertises for and selects members, makes arrange- ments for collection of subscriptions, and holds auctions for the prizes. However, such funds are of limited use to poor people, who lack both the income to pay subscriptions and the social position to gain the confidence of the company. The transition to formalised services is not inevitable. Informal and formal arrangements continue to exist side-by-side even in industrialised countries. In Oxford, UK, ROSCAS have enabled people with very limited capital of their own to increase their chances of obtaining a small business loan (Srinivasan, 1995). A detailed comparative study of credit use among low-income Pakistani, Bangladeshi, and Carribean immigrants in the UK revealed enormous differ- ences in their use of financial services. In all cases sources of credit were class- ified into high-street credit, local commercial credit, mail order, social fund, community-based credit, and 'miscellaneous' (including friends, family, and employer). Unlike the Bangladeshis, the Pakistani and Carribean respond- ents reported community-based, ROSCA-like arrangements. Bangladeshi respondents made much more use of formal bank credit than the others, although they had at least as high a proportion of applications rejected, apparently on racial grounds (Herbert and Kempson, 1996). Abugre (1994) points out that transition and change can be rapid, discon- tinuous, and turbulent rather than smooth and linear. There is therefore likely to be a multiplicity of arrangements, some of which become formalised, while others die out, and yet others are initiated. The implication for those interested in providing financial services is that such a role must be carefully thought through, and be flexible and responsive to changing circumstances. 2.5 What can be learned from informal finance? Having briefly explored the range of financial services which may exist, it is clear that informal finance is a regular feature of poor people's lives. What can be learned from this? The continuation of a large number of different forms suggest the following points (partly adapted from Adams, 1992). 23 Microfinance and Poverty Reduction There is clearly a demand for financial services The range of informal financial services available partly reflects the varied requirements which people, both rich and poor, have for financial services. They may also be explained in terms of the actions of people with excess cash seeking to earn income from lending. In some cases, especially where there is a monopoly, or collusion among providers, this can be exploitative for the borrower. Informal services available include savings facilities, provision of credit for consumption, and funding for predictable but expensive events such as marriages and funerals. This is in significant contrast to the services that NGOs have generally offered, which have usually been limited to the provision of credit for production. Transaction costs are low. Transaction costs are the costs, other than interest payments, which are incurred in making a deposit or taking a loan. They include travel, time away from other activities, related 'gifts' which might have to be offered to bank or government officials, costs in obtaining documenta- tion required, such as land certificates, and so on. Compared to formal services, local informal services generally require very little form-filling or travel. However, the advantage to the borrower of low transaction costs may be more than counterbalanced by their lack of power in setting the terms of a loan, which may be exploitative. Informal services impose their own discipline. The flow of information locally and the small number of providers of informal finance often act as powerful incentives to users to repay loans or save in a disciplined way. A ROSCA member failing to pay their instalment risks social ostracism from neighbours, friends, and relatives; they may be less likely to receive help from these people in times of severe difficulty in future. Poor people are capable of saving The evidence of informal systems disproves the assumption that poor people cannot save. Saving 'in kind' has long been a recognised part of people's livelihood management: saving in cash is a necessity of interaction with the cash economy. Indeed it is often the poorest, who are landless or for other reasons dependent on casual, poorly-paid jobs, who gain a large proportion of their incomes in cash and therefore have most need of savings facilities. The evidence shows that poor people are not only willing to save but at present often pay highly for savings facilities. 24 Informal systems are adaptable. Informal financial services The variety of forms and functions of informal finance demonstrates the adaptability of these systems to different economic conditions and changing circumstances. This contrasts with formal systems which often have to be based on a uniform delivery model. There is thus much to be learned from informal financial systems. Indeed aspects of these systems have found their way into the design of NGO and semi-formal financial services programmes. In particular, both group-based and individual-based schemes have made use of the 'insider knowledge' of other local people: individual-based schemes, such as BRI, through personal references from local representatives, and group- based schemes, such as Grameen, through self-selecting groups of borrowers (see Chapter 1). This brief overview has not identified for whom these services exist - women and men, poor or poorest. The poorest people may find it difficult to save the amount that a ROSCA requires and hence find participation a burden or are excluded. Even if there are a number of people in similar situations, they are often marginalised or isolated and lack the social networks to create their own ROSCA with a lower fee. Indebtedness may also make it difficult for the poorest to save and build up a small asset base - a situation that will be illustrated in the case of low-income and unemployed members of the Ladywood Credit Union in the UK, a case-study scheme described in Chapter 6. There are therefore limitations to the extent to which savings-based user- owned facilities can be of use to very poor people. However, systems that allow flexible amounts to be deposited are more likely to be appropriate. 2.6 Deciding when and how to intervene Before going on to discuss ways of intervening which are useful and relevant to poor people (see Chapter 3), it is necessary to issue some warnings. Several commentators, among them NGO practitioners, have questioned the appropri- ateness of NGOs acting as providers of financial services. Abugre (1992) identifies a range of dangers, and points to the dire consequences of the job being done badly: ⚫ NGOs remain averse to charging positive real interest rates and may, consciously or otherwise, undermine traditional financial systems. ⚫ NGOs do not submit themselves to the discipline required for the provision of sustainable financial services. 25 Microfinance and Poverty Reduction ⚫ Schemes are managed by entirely unprofessional and untrained staff and are often carelessly conceived, designed, and implemented. . There are cases where NGOs have flooded the market with credit, resulting in indebtedness on the part of borrowers, and potentially regressive effects on income and wealth distribution. By extending loans which poor people are unable to pay due to factors beyond their control, or which may have simply been inappropriate in the first place, NGOs can cause a level of indebtedness which may result in the borrower having to liquidate assets in order to repay. Abugre therefore warns against the hasty introduction of new financial services by NGOs and concludes that they should concentrate on what they do well, such as providing social services and acting as confidence brokers in coinmunities. Direct provision may be a risky and problematic strategy for an NGO, particularly as the NGO may not have the range of skills required to develop microfinance interventions, nor experience of the financial skills and respon- sibility required to ensure funds are properly safeguarded and accounted for. A further range of managerial skills are also necessary in managing a portfolio of financial assets such as loans and deposits. NGOS with experience of welfare and relief have more experience of channelling funds than managing them (Bouman, 1995). An NGO must ask itself whether it has the skills to become a banker.. An organisation lacking the relevant skills may consider acquiring them either through recruitment or staff development. Such a strategy itself has important consequences. These skills may be in short supply and recruit- ment prove difficult; they take time to develop and are acquired through experience as well as training. There is often a strong impetus to start work even if the skills of staff are still weak. This can endanger the intervention itself since it is at this early stage that users gain an impression of the nature of the operation, and inexperienced staff are likely to make mistakes. Embarking on direct intervention also raises questions about the long-term sustainability of the service on offer. Financial services should not be provided on a transient or temporary basis. There needs to be a degree of permanence to enable people to plan for their future finan- cial needs. Consideration of the long-term future for a system of finan- cial service provision is therefore important at the outset. Direct provision by an NGO which expects to move away from the area would seldom be appropriate. 26 Informal financial services There is a further range of issues at the level of the macro-economy which should also be considered when deciding whether to intervene. Macro- economic stability is an important pre-requisite for getting a scheme off the ground. Hyper-inflation and economic instability do not encourage individuals to save, and loans under such circumstances are difficult to manage. (However, in Mexico, while formal-sector banks were reeling from massive default caused by the high interest rates and high inflation of 1995, URAC, one of the case-study institutions discussed in Chapter 6, continued to thrive.) Political stability is also needed, since without it there is unlikely to be much confidence in the long-term future of new financial institutions. Before considering scheme design an NGO must also investigate the formal legal regulatory requirements for organisations involved in financial service provision, especially for savings (see Chapter 3). 2.6.1 Research questions on existing informal financial services In carrying out research into the services available, and how they are used, an intervener should try to find answers to a wide range of questions, such as: How do people manage their savings deposits? Are there savings banks, or deposit takers, insurance salesmen, or savings clubs? Do poor people have access to them? If not, how do they save (for example, gold, livestock). Who among the poor uses them (men, women, landless labourers, subsistence farmers etc)? (Extensive use of expensive deposit takers might indicate that the NGO should look first at the reasons why alternatives are not in place: and second at whether there is any possibility for the NGO to get involved, either as promoter or as provider, in savings collection.) How do people temporarily realise the value of assets they hold? Are there pawnbrokers or are there schemes that allow them to pawn land or other major assets (eg jewellery) safely? Who uses these services? (If such devices exist, are they exploitative or enabling? If they are clearly exploitative, there might be a case for an NGO to try to provide or promote an alternative.) How do people get access to the current value of future savings? Are there money-lenders willing to advance small loans against future savings? Are there ROSCAS or managed or commercial chits, or co-operative 2 In a background paper commissioned for the purposes of this book, Shahin Yaqub examined the 'Macroeconomic Conditions for Successful Microfinance for Poor People'. The paper is available from the Policy Department, Oxfam (UK and Ireland). 27 banks? Do poor people have access? Which poor people use them? (If money-lenders appear to be exploiting users, for example by imposing very high interest rates or linking loans to disadvantageous deals over land, labour or commodities, then there might be a case for the NGO to introduce ROSCAS or annual savings clubs, or work as a promoter of self-help groups or credit unions.) How do people make provision for known life-cycle expenses? Do they provide for daughters' marriages, their own old age and funeral, for their heirs? Are there clubs that satisfy these needs, or general savings services or insurance companies that will do as well? Are there government or employer-run schemes? Are there particular expenses for which women have responsibility? How do people cope with emergencies? What happens when a breadwinner is ill, or when a flood or drought occurs? Does the government have schemes that reach poor people in these circumstances? If not, what local provision do people make? How do small-scale entrepreneurs get access to business finance? If so, in what amounts and at what cost? Do women entrepreneurs have access? During the exploratory work done to answer these questions another set of information will come to light-the absolute quantities of cash involved in local financial intermediation. This can be of immense value to scheme designers in cases where a decision is made to intervene. For example, information about amounts repaid regularly to money-lenders will be useful in setting loan sizes and repayment schedules for loan schemes. (Source: Rutherford, 1996.) Much can be learned from the way in which people are already managing their finances. A further aspect is the social relations involved-the groups of people who get together to form ROSCAS, those from whom loans are taken, and those with whom deposits are lodged. Tierney's work on the Oxfam- funded Youth Employment Groups in Tabora Region of Tanzania demon- strates that the design of the intervention, which was based around groups of people with the same occupational background, did not correspond to the pattern of existing financial intermediation, which was organised around small kin-based groups, each including diverse enterprises. Tierney argues that 'the formation of development groups can, ironically, divert people's energy away from improving their lives, because forming the kind of groups which are eligible for financial assistance is a time-consuming activity involving skill 28 Informal financial services in manipulating and maintaining public relations' (Tierneyforthcoming). This illustrates the value of understanding how indigenous financial systems operate, before designing a new microfinance initiative. 2.7 Filling the gaps As well as alerting people to the potential pitfalls of intervention, research to answer the kind of questions suggested above is likely to identify gaps in existing services. There are many ways in which such gaps can be filled and below are some examples of financial service interventions in insurance and hire purchase which can be of use to poor people. For those agencies whose motivation is poverty reduction it is important to link the identification of gaps with a poverty analysis to determine who is excluded from existing services and how such exclusion perpetuates poverty. 2.7.1 Some examples of innovative services Hire-then-purchase for the poor in Bangladesh ACTIONAID found, through the experience of running a group- based lending programme similar to that of the Grameen Bank, that many very poor people were nervous of taking a large loan — the 5,000 taka ($125) needed to buy a rickshaw, for example — in case they were not able to repay it. AA therefore devised a bire-then- purchase scheme for such people. AA bought its own rickshaws and bired them out to group members. A rickshaw driver could hire a rickshaw from AA instead of hiring one from a local 'mohajan'. If he then decided to convert bis contract with AA from hiring to buying, a proportion of the total hiring fees he had already paid was denoted as his down-payment, and be took a regular (smaller) AA loan to pay off the rest. Door-step insurance agents, Cuttack, Orissa In Cuttack, insurance agents from the Peerless company visit house- bolds in low-income areas. They offer simple endowment schemes, which from the point of view of the customers are like accumulating fixed deposit schemes: the customer puts in a fixed amount regularly and then on maturity gets it back plus profits. Life insurance cover is included in the contract. 'Bankassurance: group-based insurance for the rural poor In Bangladesh, one insurance company is pioneering an attempt to match, in the field of insurance, Grameen Bank's success in lending. 29 Delta Life Insurance has been experimenting since 1988 with cut- price basic life-insurance for rural people. Customers are arranged in groups, there is no medical examination and no age-bar, and premiums are tiny and collected weekly. Agents are also involved in Grameen-Bank-style lending and earn an extra commission for the insurance work. In fact the insurance premiums are invested directly in lending (on which healthy interest may be earned). In 1996 Delta was looking for a big NGO partner which could offer the two services- lending and insurance- side by side. Experience so far has shown that demand for such a service is high. Delta is exploring how it can extend this initiative beyond life insurance. 2.8 Promotion: an alternative strategy for NGOS Having identified the gaps in existing financial service provision, an NGO might involve itself in promotion rather than provision. The main alternatives to direct provision of financial services are ones which involve the NGO in a transitional or support role whereby activities such as mobilisation, training, and making links to other organisations are provided. A range of possible approaches are outlined. 2.8.1 Formation of savings groups and development of internal credit facilities Where ROSCAS do not exist or have limited coverage, the NGO might act as a facilitator of their formation or enable them to develop slightly more sophisti- cated systems of internal on-lending which allows savings and loans to take on more flexible formats. This approach has been used by Friends of Women's World Banking in India. In this case the NGO is mainly involved in training and organising the groups. Self-help groups (SHGs) are NGO-led attempts to promote savings clubs, or simple forms of credit union. Those initiated by Friends of Women's World Banking in India are aimed at poor rural women. FWWB (or its partner NGOs) persuades women from the same neigh- bourhood and from similar backgrounds to form small groups of 12 to 15 members. NGO workers encourage the women to meet regularly and frequently and during these meetings the women discuss their financial problems and ways of solving them. The solution they are steered towards involves regular small savings and the immediate conversion of those savings into small loans taken by one or two members at each meeting. Care is taken to Informal financial services involve all group members in the discussion and formulation of rules (how often to meet, the interest to be charged on loans, and repayment arrangements) and then to ensure that every member experiences for herself the activities of saving and of taking and repaying a loan. The group is asked to choose leaders who are trained to manage the group's affairs: if illiteracy or very poor educational levels are a problem then rules are kept deliberately simple (fixed equal savings, and annual dividends rather than monthly interest on savings, for example). These preparations are intended to equip the group for independent survival after the NGO stops sending workers regularly to the meetings. Groups which perform well over several months are able to obtain small bulk loans made by FWWB to the group as a collective. Where there are a number of groups in an area, FWWB may help them form a federation' (apex body') to help with liquidity problems: groups with excess savings deposit them with the federa- tion which on-lends to groups with a strong demand for loans. (Source: WWB, 1993.) However, although this type of intervention can succeed with agency help, it has yet to be proved whether savings and credit groups which are promoted by outsiders can achieve long-term independence (Rutherford, 1996). A range of questions remain: can they save sufficient funds among themselves to satisfy their own demand for loans? Can external funds be introduced into these groups without destroying their independence? 2.8.2 Promotion of small-scale formalised approaches National legislation may allow for credit unions (the World Council of Credit Unions has national and regional affiliates all over the world) or thrift and credit co-operatives (as in Sri Lanka, see 3.4.2). Another approach an NGO might adopt could be the linking up of people interested in establishing such services for themselves with other credit unions or umbrella and apex bodies that are able to promote and advise on particular financial services. Oxfam Hyderabad worked with the Federation of Thrift and Credit Associations in Andhra Pradesh, encouraging exposure visits to flourishing thrift and credit societies by potential members from other areas. The members now have a source of consumption credit based on their own savings. Oxfam Hyderabad saw its support for linking potential groups with an existing thrift and credit structure as a move away from direct funding of NGOs to provide credit. (Source: Oxfam (India) Trust, 1993.) 31 2.8.3 Linking groups to the formal system Existing savings groups or ROSCAS may already have bank savings accounts but are unable to take loans because the bank does not understand their operations or believe them to be creditworthy. The NGO might work with groups to encourage them to build up savings and deposit them in formal institutions. The NGO may then be able to work with a local bank to encour- age it to extend its services to groups. In Ghana, rural banking legislation was designed to create semi- autonomous local banks which would serve people cut off from financial services. However, the banks have experienced a range of problems which led to only 23 out of a total of 123 being classified as operating satisfactorily in 1992 (Onumah, 1995). In 1991 the Garu Bank, a small rural bank set up in 1983 in Ghana, was near to collapse as a result of embezzlement and bad loans. The people of Garu persuaded a member of their own community who was working in Accra to come back to the area and become theman- ager. The Bank is a unit bank and operates relatively autonomously. Share capital of the Bank is owned by the local community, the Catholic Mission, the local Agricultural Station and a Disabled Rehabilitation Centre. Helped by an additional capital injection of $30,000 received from overseas donors via the Catholic Mission the manager trans- formed the situation, and expected to report a profit for the first time. The bank has a range of clients, including local salaried workers such as teachers and government employees. These people are good customers because they take loans which are easily recoverable in the form of deductions made from their salaries at source. Alongside these customers, the Bank provides services to some 300 farmers' groups. Some of these groups were originally formed by the local Agricultural Station and the Catholic Mission and bought shares in the Bank when it was first set up. The manager went to meet the groups to discuss their needs with them. He has developed his own approach to the groups, and stresses that they should be concerned with working together rather than just obtaining credit. He has set up his own criteria for lending to the groups: savings balances of at least 10 per cent of the loan amount; regularity of savings as an indicator of group cohesion; and that the group should have been operating for at least six months. Repayment of the loan on time results in almost automatic qualification for a new loan the following year (although be bad refused loans to a number of groups the previous year due to poor performance). (Source: Abugre, Johnson et al, 1995.)

Answer the following question using only information from the text included below. You must not utilize any other sources or your own reasoning in your response. What are some examples of informal financial services? Current debates in microfinance 1 1.1 Subsidised credit provision From the 1950s, governments and international aid donors subsidised credit delivery to small farmers in rural areas of many developing countries. It was assumed that poor people found great difficulty in obtaining adequate volumes of credit and were charged high rates of interest by monopolistic money-lenders. Development finance institutions, such as Agricultural Development Banks, were responsible for the delivery of cheap credit to poor farmers. These institutions attempted to supervise the uses to which loans were put, and repayment schedules were based on the expected income flow from the investment. Returns were often overestimated. For example, calculations would be based on agricultural yields for good years (Adams and Von Pischke, 1992). As a result, loans were often not repaid. The credibility and financial viability of these subsidised credit schemes were further weakened by the use of public money to waive outstanding and overdue loans at election time (Adams and Von Pischke, 1992; Lipton, 1996; Wiggins and Rogaly, 1989). A dependence on the fluctuating whims of governments and donors, together with poor investment decisions and low repayment rates made many of these development finance institutions unable to sustain their lend- ing programmes. Credit provision for poor people was transitory and limited. 1.2 The move to market-based solutions This model of subsidised credit was subjected to steady criticism from the mid-1970s as donors and other resource allocators switched attention from state intervention to market-based solutions. Policy-makers were reminded 5 Microfinance and Poverty Reduction that credit could also be described as debt and that the over-supply of subsidised credit without realistic assessment of people's ability to repay could result in impoverishment for borrowers. At the same time the concept of 'transaction costs', and the notion that full information about borrowers was not available to lenders, were used by the opponents of subsidised credit to justify the high interest-rates charged by money-lenders. Lending money carries with it the risk of non-repayment. In order to know who is creditworthy and who is not, and so reduce this risk, the lender screens potential borrowers. This involves gathering information on the circumstances of individuals, which may not be easy to obtain. Then enforcement costs are incurred to ensure repayment. Through this process risks are reduced, though not eliminated. Where a loan is disbursed on condition that it is used for a particular purpose, supervision costs also arise. Using these tools of analysis it was argued that private money-lenders charged interest rates which were higher than formal bank-rates because of the high costs they faced in terms of risk, particularly when lending without physical collateral. At the same time, it was argued that money-lenders were an efficient source of credit because their greater knowledge of the people to whom they were lending lowered screening costs. Moreover, potential borrowers faced high transaction costs when they sought loans from formal-sector finance institutions. These costs included the time, travel, and paperwork involved in obtaining credit, and were often pro- hibitive for poor clients, especially those most geographically isolated. On the basis of this analysis, a group of economists based at Ohio State University (USA), notably Dale Adams and J D Von Pischke, put forward the view that the provision of credit should be left almost entirely to the private sector. In concentrating on the problems of publicly subsidised credit, these economists ignored the social ties, power relations, and coercion associated with the activities of money-lenders. However, detailed micro-level research has demonstrated the widespread use of interlocked' contracts to force exchange to the disadvantage of poor people (Bhaduri, 1981). Powerful local people, including landlords, employers, and traders, are able to influence the terms of loans made to tenants, workers, and small producers via conditions set in transactions involving land, labour, or crops. For example, traders frequently lend working capital to small farmers on condition that their crops are sold to that trader at a pre-determined price. Similarly, loans are made to workers against the promise of labour to be provided at below the going rate at a set future date (Rogaly, 1996b). Against the background of these debates, recent developments in the design of microfinance schemes have generated an understandably high degree of excitement. This is because innovative features in design have 6 Current debates in microfinance reduced the costs and risks of making loans to poor and isolated people, and made financial services available to people who were previously excluded. 1.3 Making use of social collateral There was little knowledge among formal-sector financial intermediaries of alternatives to physical collateral, until the 1970s, when the Grameen Bank in Bangladesh began using 'peer-group monitoring' to reduce lending risk. The model for credit delivery in the Grameen Bank is as follows: • Groups of five self-select themselves; men's and women's group are kept separate but the members of a single group should have a similar economic background. • Membership is restricted to those with assets worth less than half an acre of land. ⚫ Activities begin with savings of Taka 1 per week per person and these savings remain compulsory throughout membership. • Loans are made to two members at a time and must be repaid in equal instalments over 50 weeks. . Each time a loan is taken the borrower must pay 5 per cent of the loan amount into a group fund. • The group is ultimately responsible for repayment if the individual defaults. • Between five and eight groups form a 'development centre' led by a chair- person and secretary and assisted by a Grameen Bank staff member. • Attendance at weekly group and centre meetings is compulsory. • All transactions are openly conducted at centre meetings. • Each member may purchase a share in the Bank worth Taka 100 Through this system the Grameen Bank has provided credit to over 2 million people in Bangladesh (94 per cent women) with a very low default rate. (Source: Khandker, Khalily and Khan, 1995.) However, peer-group monitoring has not proved necessary to other instit- utions seeking to do away with physical collateral. In Indonesia, government- sponsored banks have successfully used character references and locally- recruited lending agents (Chaves and Gonzales Vega, 1996). The peer-group 7 Microfinance and Poverty Reduction method of Grameen and the individual-user approach of the Bank Rakyat Indonesia (see 1.4) can both be seen as attempts to lower screening costs by using local 'insider' information about the creditworthiness of borrowers. The degree to which Grameen Bank employees themselves implement peer-group monitoring has recently been questioned. It is argued that the reason for the Grameen Bank's high repayment rates is the practice of weekly public meetings at which attendance is compulsory, for the payment of loan instalments and the collection of savings. The meetings reinforce a culture of discipline, routine payments, and staff accountability (Jain, 1996). Another means of improving loan recovery is to insist on regularity of repayment. This is likely to reflect the actual income-flow of the borrower much better than a lump-sum demand at the end of the loan period. Borrowers can make repayments out of their normal income rather than relying on the returns from a new-often untested-mini-business. Neverthe- less, where seasonal agriculture is the main source of income, and borrowers face seasonal hardship, regular repayment scheduling may cause problems. Microfinance specialists have argued that the prospects for scheme's stability are improved by innovations such as social collateral and regular repayments instalments. Indeed, financial sustainability has become an important goal in itself. To achieve sustainability, microfinance institutions, be they NGOs, government agencies, or commercial banks, need to ensure that the costs of providing the service are kept low and are covered by income earned through interest and fees on loans (see Havers, 1996). As microfinance deals, by definition, with small loans, the income generated through interest payments is also small in comparison with administration costs. To generate profits, therefore, it is necessary to increase scale - in other words, to lend to a large number of people (Otero and Rhyne, 1994). 1.4 Savings The regular repayments on loans required by large non-governmental micro- finance institutions in Bangladesh (including BRAC, ASA and Grameen) provide evidence that poor people can save in cash (Rutherford, 1995a). These intensive repayment regimes are very similar to those of rotating savings and credit associations: steady weekly payments, enforced by social collateral, in return for a lump sum. Loans made are, in reality, advances against this stream of savings. By insisting on regular savings, microfinance institutions can screen out some potential defaulters, build up the financial security of individuals, increase funds available for lending, and develop among members a degree of identification with the financial health of the institution. People involved in 8 Current debates in microfinance such schemes may previously have been unable to reach formal-sector banks, complete their procedures, qualify for loans or open savings accounts. 'A savings facility is an extremely valuable service in its own right, which often attracts many more clients than a credit programme, particularly from among the poorest' (Hulme and Mosley, 1996, p147). This evidence that poor people can save in cash has opened up further debate. A distinction is made between schemes in which borrowers must save small and regular amounts in order to obtain loans (termed 'compulsory' saving) and those which offer flexible savings facilities. In the latter case people can deposit and withdraw cash in whatever amounts, and as often, as they wish. This distinction is made especially strongly by Robinson (1995) in her account of the Bank Rakyat Indonesia. The BRI local banking system has about six times as many deposit accounts as loans. On 31 December 1993, BRI's local banking system had $2.1 billion in deposits. These were all voluntary savings. By 31 December 1995, there were 14.5 million savings accounts. Savers with BRI bave access to savings whenever they want. BRI deals with individuals rather than groups. Its savings programme was designed specifically to meet local demand for security, convenience of location, and choice of savings instruments offering different mixtures of liquidity and returns. BRI's local banking system has a loan limit of about $11,000. The idea is that good borrowers should not be forced to leave until they can qualify for the loans provided by ordinary commercial banks. In addition, BRI has a system which gives its borrowers an incentive to repay on time. An additional 25 per cent of the interest rate is added to the monthly payment. This amount is paid back to borrowers at the end of the loan period if they have made every payment in full and on time. There is a corresponding in-built penalty for those who have not. (Source: Robinson, 1994.) Robinson argues that there is an enormous unmet demand for flexible savings services. However, she also warns that managing a savings system of this type is much more complex than running a simple credit programme. Schemes which operate under these 'new' savings and credit technologies are an improvement on the old model of subsidised agricultural and micro- enterprise finance. The story of how they have succeeded in reaching poor people is now the subject of a large literature (for example, Rutherford, 1995b; Hulme and Mosley, 1996; Mansell-Carstens, 1995). That many more poor people can now obtain financial services is a major achievement of these 9 Microfinance and Poverty Reduction schemes. However, the questions of which poor people have been reached, and of whether poverty has been reduced, still remain. 1.5 Can microfinance interventions reduce poverty? If poverty is understood as low levels of annual income per household, reducing poverty is about raising average income levels. If a particular level of annual income per head is used as a poverty line, poverty reduction could be measured by counting the number or proportion of people who cross that line-who are promoted out of poverty. Providers of financial services who aim to enable people to cross such a poverty line have focused on credit, in particular credit for small enterprises, including agricultural production. However, attention to annual income can obscure fluctuations in that income during any given year. Poverty can also be understood as vulner- ability to downward fluctuations in income. Such fluctuations can be relat- ively predictable, such as the seasonal decline in employment for agricultural workers, or a shortage of income and trading opportunities in the dry season or before harvest. Alternatively, fluctuations in income may result from unexpected shocks such as crop failure, illness, funeral expenses or loss of an asset such as livestock through theft or death, or a natural disaster such as a cyclone (Montgomery, 1996). Vulnerability can be heightened by the lack of saleable or pawnable assets and by debt obligations. Interventions which reduce such vulnerability and protect livelihoods also reduce poverty. 1.5.1 Poverty as powerlessness A further dimension of poverty which is often the focus of NGO interventions is powerlessness, whether in an absolute sense or in relation to others. Economic inequality between and within households is likely to be associated with concentrations of political and social power. Inequality can increase whenever better-off people are able to improve their incomes faster than others. Even if the absolute level of material well-being of the worst-off people does not change, relative poverty (Beck, 1994) may increase, and with it a sense of powerlessness among very poor people. Power relations are partly determined by norms of expected behaviour. Neither the relations nor the norms are static; they are contested and change over time. Powerlessness can be experienced in a variety of situations: within the household, as a result of differences in gender and age; and within the community, between socio-economic groups, as a result of caste, ethnicity, and wealth. Defining poverty in terms of power relations implies that assessment of the impact of microfinance interventions should focus on their 10 Current debates in microfinance influence on social relations and the circumstances which reproduce them. Even in a similar geographical and historical context, it is important to disting- uish between the ways in which specific groups of poor people (women and men, landed and landless, particular ethnic groups) are able to benefit from financial services or are excluded from doing so. 1.5.2 Credit for micro-enterprises While there are methodological difficulties involved in measuring increases in incomes brought about by the provision of credit (see further discussion in Chapter 5), studies have demonstrated that the availability of credit for micro- enterprises can have positive effects. A recent survey collected data from government, NGOs, and banks involved in providing financial services for poor people. Twelve programmes were selected from seven countries (six of these are included in Table 1, Annex 1). Households which had received credit were compared with households which had not. The results demon- strated that credit provision can enable household incomes to rise. However, taking the analysis further, Hulme and Mosley demonstrated that the better-off the borrower, the greater the increase in income from a micro- enterprise loan. Borrowers who already have assets and skills are able to make better use of credit. The poorest are less able to take risks or use credit to increase their income. Indeed, some of the poorest borrowers interviewed became worse off as a result of micro-enterprise credit, which exposed these vulnerable people to high risks. For them, business failure was more likely to provoke a livelihood crisis than it was for borrowers with a more secure asset base. Specific crises included bankruptcy, forced seizure of assets, and unofficial pledging of assets to other members of a borrowing group. There have even been reports of suicide following peer-group pressure to repay failed loans (Hulme and Mosley, 1996, pp120-122). A much smaller survey comparing micro-enterprise programmes in El Salvador and Vanuatu found that the development of successful enterprises and the improvement of the incomes of very poor people were conflicting rather than complementary objectives. By selecting those most likely to be successful for credit and training, the programmes inevitably moved away from working with the poorest people (Tomlinson, 1995). Reviews of Oxfam's experiences with income-generating projects for women raised serious questions about the profitability of such activities. Full input costings, which would have revealed many income-generating projects as loss- making, were not carried out. Omissions included depreciation on capital, the opportunity cost of labour (the earnings participants could have had through spending the time on other activities), and subsidisation of income- 11 Microfinance and Poverty Reduction generating projects with income from other sources. Market research and training in other business skills had often been inadequate (Piza Lopez and March, 1990; Mukhopadhyay and March, 1992). 1.5.3 Reaching the poorest Whether income promotion is based on loans for individual micro-enterprises or on group-based income generation projects, its appropriateness as a strategy for poverty reduction in the case of the poorest people is questionable. Other evidence suggests that self-selected groups for peer-monitoring have not been inclusive of the poorest people (Montgomery, 1995). People select those with whom they want to form a group on the basis of their own know- ledge of the likelihood that these people will make timely payment of loan and savings instalments: X will only have Y in her group if she believes Y is capable of making regular repayments and has much to lose from the social ostracism associated with default. This system might well be expected to lead to the exclusion of the poorest (Montgomery, op. cit.). Even the low asset and land-holding ceiling which the big microfinance institutions in Bangladesh have successfully used to target loans away from better-off people has not necessarily meant that the poorest, who are often landless, are included (Osmani, 1989). So while the innovations referred to earlier appear to have made loans more available to poor people, there is still debate over the design of appro- priate financial services for the poorest. Hulme and Mosley's study strongly suggests that providing credit for micro-enterprises is unlikely to help the poorest people to increase their incomes. However, detailed research with users has found that some design features of savings and credit schemes are able to meet the needs of very poor people. For example, it was found that easy access to savings and the provision of emergency loans by SANASA (see 3.4.2) enabled poor people to cope better with seasonal income fluctuations (Montgomery, 1996). Microfinance specialists increasingly, therefore, view improvements in economic security income protection rather than promotion (Dreze and Sen, 1989) as the first step in poverty reduction. ...from the perspective of poverty reduction, access to reliable, monetized savings facilities can help the poor smooth consumption over periods of cyclical or unexpected crises, thus greatly improving their economic security.' It is only when people have some economic security that 'access to credit can help them move out of poverty by improving the productivity of their enterprises or creating new sources of livelihood' (Bennet and Cuevas, 1996, authors' emphasis). Current debates in microfinance 1.6 Financial interventions and social change Interventions have an impact on social relations partly through their econ- omic effects. In many instances implementors of credit schemes have claimed that the work will lead to progressive social change, for example by empow- ering women and changing gender relations in the household and in the community (Ackerly, 1995). In five out of the six schemes summarised in Table 1 (Annex 1), over half of the borrowers were women. Much of the work that has been done in assessing the impact of credit programmes on women has been in Bangladesh. One approach was to look at the control women retained over loans extended to them by four different credit programmes: the Grameen Bank, BRAC, a large government scheme (the Rural Poor Programme RD-12), and a small NGO (Thangemara Mahila Senbuj Sengstha) (Goetz and Sen Gupta, 1996). Results suggested that women retained significant control over the use to which the loan was put in 37 per cent of cases; 63 per cent fell into the categories of partial, limited or no control over loan use. Goetz and Sen Gupta found single, divorced, and widowed women more likely to retain control than others. Control was also retained more often when loan sizes were small and when loan use was based on activities which did not challenge notions of appropriate work for women and men. The question of whether women were empowered is not answered: even when they did not control loans, they may have used the fact that the loan had been disbursed to them as women to increase their status and strengthen their position in the household. However, in some cases women reported an increase in domestic violence because of disputes over cash for repayment instalments. A second major piece of research has assessed the effect of Grameen and BRAC programmes on eight indicators of women's empowerment: mobility, economic security, ability to make small purchases, ability to make larger purchases, involvement in major household decisions, relative freedom from domination by the family, political and legal awareness, and participation in public protests and political campaigning (Hashemi et al, 1996). The study concludes that, on balance, access to credit has enabled women to negotiate within the household to improve their position. However, unlike the Goetz and Sen Gupta study, which is based on 275 detailed loan-use histories, Hashemi et al attempted to compare villages where Grameen or BRAC were present with villages where they were not. Because of difficulties inherent in finding perfect control villages (which the authors acknowledge), the conclusions of the study do not signify the end of the debate. It has also been argued that focusing on women is much more to do with financial objectives than with the aim of empowerment. According to 13 Microfinance and Poverty Reduction Rutherford (1995b) the real reasons for targeting women in Bangladesh are that they are seen as accessible (being at home during working hours); more likely to repay on time; more pliable and patient than men; and cheaper to service (as mainly female staff can be hired). Thus the process of loan supervision and recovery may be deliberately internalised inside the household (Goetz and Sen Gupta, op. cit.). Goetz and Sen Gupta do not use this as an argument against the provision of finance for women in Bangladesh, but rather suggest that to avoid aggravating gender- based conflict, loans should be given to men directly as well as to women and, at the same time, that efforts should be made to change men's attitudes to women's worth. 1.7 Treading carefully in microfinance interventions This brief summary of evidence and argument suggests that microfinance interventions may increase incomes, contribute to individual and household livelihood security, and change social relations for the better. But that they can not always be assumed to be doing so. Financial services are not always the most appropriate intervention. The poorest, in particular, often face pressing needs in terms of primary health care, education, and employment opportunities. Lipton has recently argued for anti-poverty resources to be allocated across sectors on the basis that a concentration on a single interven- tion mechanism, say credit, is much less effective in poverty reduction than simultaneous credit, primary health, and education work, even if this entails narrowing geographical focus (op. cit.). The particular combinations which will be most effective will depend on the nature of poverty in a specific context. Although microfinance provision appears to be evolving towards greater sustainability, relevance, and usefulness, there are few certainties and the search for better practice continues. Decisions on whether and how to intervene in local financial markets should not be taken without prior knowledge of the working of those markets. If the intervention is intended to reduce poverty, it is especially important to know the degree to which poor people use existing services and on what terms. Only then can an intervening agency or bank make an informed decision on whether their work is likely to augment or displace existing 'pro-poor' financial services. If the terms of informal financial trans- actions are likely to work against the interests of poor people (cases in which the stereotype of 'the wicked money-lender' corresponds to reality) the inter- vention may attempt to compete with and possibly replace part of the informal system. However, making such an informed assessment is not straight- forward, as one study of the power relations between informal financial 14 Current debates in microfinance service providers and agricultural producers in Tamil Nadu demonstrated. Grain merchants based in the market town of Dindigul were found to dictate the terms of product sale when lending working capital to very small-scale farmers, but to be much the weaker party when lending to larger-scale farmers (Rogaly, 1985). The structure of a credit market can change, partly under the influence of outside intervention. Rutherford has studied the changing market in financial services for poor people in Bangladesh. Competition between NGOs is leading to users being less subservient to NGO staff and protesting about unpopular financial obligations, such as the 5 per cent deducted from loans by Grameen for a 'group fund'. Private individuals have set up offices imitating the Grameen style but charging higher interest rates on loans than the big NGOS, and also offering higher rates on savings deposits. Private urban finance companies have expanded. Despite the tendency for NGOs to become more like banks, other formal-sector lenders are still reluctant to lend to poor people (see also McGregor, 1994). The expansion of NGO credit in Bangladesh has been made possible by the flood of donor money to that country. One study of BRAC showed that loan disbursal and recovery had become more important than group forma- tion (Montgomery, 1996). In 1992, Grameen Bank and BRAC employees were found to be offering 'immediate loans' to women in villages where smaller NGOs had been attempting longer-term group-based finance (Ebdon, 1995). Ebdon attributed this behaviour to fairly strict targets for loan disbursal in the case of BRAC, and in both cases to an imperative for job security for staff and a desire on the part of the organisations to expand their influence and strengthen their reputations (p52). This anxiety to increase the number of users can undercut the very basis of the new model: the creation of sustainable financial institutions. Studies of credit schemes have consistently demonstrated that unless borrowers and savers believed they would benefit from the long-term survival of the institution, and have a sense of ownership, repayment rates would decline (Rogaly, 1991; Copestake, 1996a). The sense of ownership is weakened by attempts by large microfinance institutions in Bangladesh to claim territory by encroachment. In India, in the absence of equivalent flows of external finance, thrift and credit co-operatives based much more on borrowers' requirements have emerged (Rutherford, 1995b, p136). An understanding of the way in which the institutions themselves change and respond to incentives is therefore necessary for the design of relevant anti-poverty interventions, including financial services. 15 2 Informal financial services 2.1 Introduction In recent years research into informal financial services and systems has significantly deepened understanding of the way they operate and their strengths and weaknesses. A simplistic belief that local money-lenders charged extortionate interest rates lay behind the provision of subsidised finance in the past. More thorough investigation has highlighted a range of savings, credit, and insurance facilities accessible to poor people. The appar- ently usurious interest charges reportedly made by private money-lenders may be explainable in terms of transaction costs, lack of information, and high risk. Informal financial services may be well-equipped, because of local 'insider' knowledge, and lower overheads, to respond to the requirements of poor people; they may also be exploitative. This chapter starts with a brief overview of the types of informal services that have been found to exist in a wide variety of countries and social contexts. Some of the broad characteristics of these services are identified, and lessons drawn for the design of NGO or semi-formal systems. In describ- ing informal financial services it is useful to distinguish between those which are owned by their users and those which are offered by an individual, usually on a profit-making basis. The distinction can be a helpful one in analysing the ways in which financial services enable or exploit poor people. NGOs considering microfinance interventions need first to find out what informal financial services are available, and how they operate. Such services are capable of supporting poor people's livelihoods as well as perpetuating 1 This chapter draws heavily on a background paper commissioned for the purposes of this book: A Critical Typology of Financial Services for the Poor, Stuart Rutherford, November 1996. Examples are drawn from Rutherford's own experience unless otherwise stated. 16 Informal financial services structures which undermine them. It is necessary, therefore, to understand under what circumstances and to what degree these services are enabling or exploitative for poor people. On the whole, user-owned services are likely to be more enabling than services provided for profit. Investigating the scope and nature of existing services is an essential pre- liminary before considering whether an intervention is necessary. However, NGOs themselves may not have the right skills to become direct providers of financial services. Furthermore, financial services are needed by poor people on a permanent basis to enable them to plan and manage their finances; NGO programmes which might be here today and gone tomorrow may be an inap- propriate means through which to provide them. Therefore NGOs should seriously consider whether direct intervention is in fact the best response for them to make. The chapter closes by discussing alternative strategies NGOs might employ. 2.2 User-owned informal financial services Systems which facilitate financial transactions and are owned by their users are many and varied, and range from simple reciprocal arrangements between neighbours, savings clubs and rotating savings and credit associa- tions (ROSCAS), to forms of insurance, building societies, and systems of co- operative business finance. An example of each of these types is described below. All of these systems can be found in a variety of country settings. Rotating savings and credit associations (ROSCAS) in particular, are an extremely common phenomenon. They exist in almost every country (for example, 'partners' in Jamaica and Britain, bui in Vietnam, and njangi in Cameroon). (See Bouman, 1995; Ardener and Burman, 1995 for detailed and extensive surveys of ROSCA operations in a range of settings.) The principle is very simple: a number of people agree to save a fixed amount of money at regular intervals; at each meeting, for example weekly, each member contri- butes an agreed amount, resulting in a single lump sum becoming available, which is then allocated to one of the members. There are three basic varia- tions in the way in which this lump sum or 'prize' is allocated. First, it can be allocated on the basis of strict rotation between members of the group; second, on the basis of a lottery of members; third, it may be auctioned to the member who is willing to accept the biggest discount. The group will usually meet (but does not always need to) and undertake this transaction on as many occasions as there are members of the group, thus ensuring that each member gets the 'prize' once. The ROSCA demonstrates the basic principle of financial intermediation: collecting many small savings from many people, turning this into a lump sum for one person, and repeating this procedure over time. 17 Microfinance and Poverty Reduction ROSCA finance is used for many purposes. Some ROSCAS operate to enable an asset to be purchased, such as a rickshaw or fishing equipment for each member, and may have been set up specifically for the purpose. 'Merry- go-rounds', as ROSCAS are called among Kikuyu women in Kenya, are sometimes used by women as a means of accumulating enough money to buy new household utensils or clothes. The technology of the ROSCA is not unique to poor communities but is also used by salaried professionals to purchase major consumption items or assets such as refrigerators or cars. A further example of a user-owned device is the insurance fund which makes pay-outs conditional on certain circumstances occurring. These are int- ended to cover large expenses such as those connected with marriage or death. 2.2.1 Some examples of user-owned financial services Neighbourhood reciprocity in Southern India Reciprocal lending may be extended to involve several or even all the members of a community. Among Moslems in Kerala State in southern India kuri kalyanam are invitations to a feast to which the guest is expected to bring a cash gift. When the host in his turn is invited to a feast by one of the guests he is expected to return double the amount (less if he is perceived as poor). In Vietnam one kind of hui (a generic name for various financial devices) involves a similar pooling of resources for one person on one occasion to be reciprocated later by others, at different times. Rickshaw ROSCAS in Bangladesh Very poor men driven by poverty from their home villages to the Bangladesh capital, Dhaka, often earn a living there by driving bired rickshaws. In the last ten years they have begun to run ROSCAS. A group of drivers forms, and each driver saves a set amount from his daily takings. When the fund is large enough (this usually takes about 15 days) a rickshaw is bought and distributed by lottery to one of the members. In between prizes' the cash is held by a trustworthy outsider, usually a local shopkeeper from whom the members buy their tea or cigarettes. In a further adaptation, those who have already received their rickshaw double their daily contribution. This progressively reduces the time-gap between prizes, and is seen as a fair way of rewarding those members who win the lottery late in the cycle, because their gross contribution is smaller than earlier winners. The extra payment made by the winners is roughly equivalent to what they save by no longer having to hire a rickshaw. 18 An accumulating savings club in Mexico Informal financial services In towns and villages in Mexico neighbours place frequent but irregular savings with trusted shopkeepers. Just before Christmas, the cash is returned to the saver. No interest is paid, but the saver has a lump sum to spend, and the shopkeeper has had the use of the money over the year and can now look forward to a good sales season. Building societies for the middle classes in Bangladesh In a lower-middle-class area of Dhaka, 165 employees in the Public Works Department belong to their own building society' which was started over 16 years ago. Each saves 200 taka ($5) a month out of his wages. As the cash accumulates it is lent out to members, who buy land and building materials. Interest rates are high and interest on the out- standing balance has to be paid each month, to encourage modest loans and rapid repayment. But loan sizes are generous and such workers would have few or no alternative sources for loans of this kind. Popular insurance: funeral funds (iddir) in Ethiopia Originally burial societies, iddir have extended to provide a wide range of insurance services in urban Ethiopia. Aredo (1993), study- ing these in Addis Ababa, estimated that 50 per cent of urban house- holds were members of some kind of iddir. Groups of people come together on the basis of location, occupation, friendship or family ties. Each iddir sets its own rules and regulations but usually pays out for funeral expenses or financial assistance to families of the deceased, and sometimes to cover other costs, such as medical expenses and losses due to fire or theft. 2.3 Informal financial services for profit Those offering informal financial services for profit fall into two groups: deposit takers (often also called money-guards) and lenders. What is most interesting about the situation of deposit takers is that, as in the Nigerian example below, savers usually pay for the service by obtaining a negative interest rate on their funds. This demonstrates the pressing need that people have for places to put their savings which are safe and secure not only from physical risks such as theft, fire or flood, but also from the demands of their family. For women, in particular, the ability to save small amounts in places to which their husbands and families cannot gain access (although they might know about them) has been shown to be particularly important. It may enable them to meet obligations in the family or household, such as the payment of children's school fees, for which they have particular responsibility. 19 Microfinance and Poverty Reduction Forms of lending also operate in a variety of ways, such as money-lenders; pawnbrokers, who take collateral in the form of physical assets; and forms of trade credit and hire purchase. The term 'money-lender' can cause confusion because it conjures up the image of a class of people whose main source of income is usury. In reality, many small farmers, for example, obtain credit from employers, landlords, traders, relatives, and other people who combine a number of economic activities. In some places money-lenders may be a more professionalised class, such as the Tamilians' in Cochin described below, but even in this case it is not necessarily their main source of income. Lending money can be exploitative of, as well as enabling for, poor people. People facing seasonal shortages may have only one source of credit, for example, an employer. The employer may agree to provide a loan, but only if the borrower promises to work when required at below the going wage-rate. As described below for Indonesia, crop traders may provide producers with seasonal credit on the understanding that the crop is sold through the same trader at low post-harvest prices. Tied credit of this type, whether in cash or kind, may be the only means of survival for poor people. But arrangements such as these can maintain and even exacerbate inequalities in power and position. In contrast, user-owned devices are likely to be more supportive and enabling, because the profits made are pooled, and shared or fed back into the system, and ownership and control of the funds are in the hands of the users. Such devices are unlikely to be exploitative of those involved, although they may widen inequalities between users and non-users. The comparison with services for profit is clear. However, loans from private lenders after harvest may enable small traders to make the most of the increased liquidity in the local economy. This emphasises the need for interveners to understand the workings of real markets and to question untested assumptions. It is essential to find out for which groups of poor people-women, men, landless labourers, subsistence farmers, migrant workers and under what circumstances these arrange- ments may be no more than a means of survival, while supporting wealth creation for others. 2.3.1 Some examples of informal financial services provided for profit Deposit takers: a mobile alajo in Nigeria One consequence of Nigeria's current political difficulties is a drop in public confidence in formal banks, according to Gemini News. This has allowed an old tradition to flourish again- alajos, or peripatetic deposit takers. Idowu Alakpere uses a bicycle to go 20 Informal financial services door-to-door round the outer suburb of Lagos where he lives. He has 500 customers who each save about 10 or 15 naira with him (about 50 to 75 cents US) at each daily visit. Customers withdraw money whenever they like, and Idowu charges them one day's savings per month, which he deducts from the withdrawal. Since deposits are made evenly over the month, the negative interest rate for one-month deposits is 1/15, or 6.6 per cent a month, an Annual Percentage Rate (APR) of 80 per cent. Some alajos, including Idowu, store the cash in a reliable bank, others use it to make loans. The Gemini News reporter was told by many local people that they trusted these alajos more than banks. When it was pointed out that some alajos are dishonest, they retorted that so are many banks. Professional money-lenders in Cochin, India 'Tamilians' provide a money-lending service to poor slum dwellers on a daily basis. They have set terms, which are well-known all over Cochin. For each 100 rupees lent, 3 rupees are deducted at source as a fee. Thereafter, 12.50 rupees per week must be repaid for ten weeks. This works out at an APR of 300 per cent (28 rupees paid on an average size loan of 48.50 rupees [97/2) for 10/52 of a year). Most non-poor observers regard this rate as outrageously exploitative. However, poor users of the service tend to take a favourable view of it. The 'Tamilians' do not needlessly harass their clients over repay- ment but take an 'understanding' view which includes a willingness to accept loan losses. These money-lenders know their clients well and (out of self-interest) will not lend more than they think the client can repay out of normal income over the next ten weeks. Lending against collateral: pawnbrokers in Western India Residents of the slums of Vijayawada use their local pawnbroker when they need money quickly. He is reliably available at his gold- smithing shop and he charges 3 per cent a month for loans pledged against gold, 5 per cent for silver and 9 per cent for brass. The inclu- sion of brass means that even the very poor can get a small advance by pawning kitchen pots and pans. He lends up to two-thirds the value of the pawn. He gives a receipt, and because the borrower can be sure of getting her pawn back when she repays the loan, she can risk pawning objects of sentimental value. Unlike those who lend without collateral the broker does not need to know his clients well: the unambiguous collateral provided by the pawn means that the broker can lend to more or less anyone at any time. 21 Microfinance and Poverty Reduction Advance crop sales in Indonesia A practice common in many countries is known as ijon in some areas of Indonesia. Farmers often need cash to get them through the 'bungry' season when their main crop is in the ground and there is not much else to do except sit and wait. They are forced to make an advance sale of the crop, usually to a grain buyer or his agent. Ijon transactions of this sort, if seen as loans, show an interest rate of anything from 10 to 40 per cent a month. (Source: Bouman and Moll in Adams and Fitchett, 1992.) Two examples of trade credit In many markets it is common to see poor people squatting on the ground with a small amount of fertiliser spread out on a mat. The fertiliser doesn't necessarily belong to the man or woman (or, often, child). Lacking capital themselves to buy stock, such people obtain the fertiliser on credit from a nearby shop. At the close of the market they return the money from sales and any balance of the stock to the shopkeeper, retaining a small proportion of the money. The system allows people to trade (safely if not profitably) without capital, and gives the shopkeeper a cheap extra outlet. The dadon credit system used to finance prawn cultivation in Bangladesh is an example of a trading system in which credit is passed on through a chain of intermediaries between the prawn farmer and exporters to Europe. The prawn market is a highly com- petitive business in which everyone in the chain is short of capital. The 'commission agent' at the port buys prawns on behalf of the exporters in the capital. To ensure their share of the market they provide credit early in the season which finds its way through a number of intermediaries before reaching the hands of the farmer. The intermediaries are 'depot' owners, then farias', or merchants, and finally local traders, who in turn lend to the farmers. In accepting the credit the farmer commits himself to selling exclusively to this particular trader. 2.4 Turning the informal into the formal In some countries such informal systems have evolved into formal systems which have had a major impact on their users. In the UK, for example, 'mutual' or friendly societies which began as small thrift groups in the nineteenth century turned into building societies in the first half of the twentieth, and have been the main source of housing finance for 50 years. Informal financial services There are further examples of such informal systems becoming increas- ingly formalised. Aredo (1993) reports that the iddir in Addis Ababa run by the Ethiopia Teachers' Association is of the scale of a medium-size insurance business. In Cameroon some of the traditional ROSCAS known as njangi have evolved into small banks offering finance for small businesses which have difficulty using formal banks (Haggblade, 1978). ROSCAS may thus be a transitional phenomenon. Chit funds in India are a formalised version of a ROSCA, for which govern- ment legislation exists. In contrast to the ROSCA, members of the chit fund do not normally know each other and are merely customers of the chit companies. The company advertises for and selects members, makes arrange- ments for collection of subscriptions, and holds auctions for the prizes. However, such funds are of limited use to poor people, who lack both the income to pay subscriptions and the social position to gain the confidence of the company. The transition to formalised services is not inevitable. Informal and formal arrangements continue to exist side-by-side even in industrialised countries. In Oxford, UK, ROSCAS have enabled people with very limited capital of their own to increase their chances of obtaining a small business loan (Srinivasan, 1995). A detailed comparative study of credit use among low-income Pakistani, Bangladeshi, and Carribean immigrants in the UK revealed enormous differ- ences in their use of financial services. In all cases sources of credit were class- ified into high-street credit, local commercial credit, mail order, social fund, community-based credit, and 'miscellaneous' (including friends, family, and employer). Unlike the Bangladeshis, the Pakistani and Carribean respond- ents reported community-based, ROSCA-like arrangements. Bangladeshi respondents made much more use of formal bank credit than the others, although they had at least as high a proportion of applications rejected, apparently on racial grounds (Herbert and Kempson, 1996). Abugre (1994) points out that transition and change can be rapid, discon- tinuous, and turbulent rather than smooth and linear. There is therefore likely to be a multiplicity of arrangements, some of which become formalised, while others die out, and yet others are initiated. The implication for those interested in providing financial services is that such a role must be carefully thought through, and be flexible and responsive to changing circumstances. 2.5 What can be learned from informal finance? Having briefly explored the range of financial services which may exist, it is clear that informal finance is a regular feature of poor people's lives. What can be learned from this? The continuation of a large number of different forms suggest the following points (partly adapted from Adams, 1992). 23 Microfinance and Poverty Reduction There is clearly a demand for financial services The range of informal financial services available partly reflects the varied requirements which people, both rich and poor, have for financial services. They may also be explained in terms of the actions of people with excess cash seeking to earn income from lending. In some cases, especially where there is a monopoly, or collusion among providers, this can be exploitative for the borrower. Informal services available include savings facilities, provision of credit for consumption, and funding for predictable but expensive events such as marriages and funerals. This is in significant contrast to the services that NGOs have generally offered, which have usually been limited to the provision of credit for production. Transaction costs are low. Transaction costs are the costs, other than interest payments, which are incurred in making a deposit or taking a loan. They include travel, time away from other activities, related 'gifts' which might have to be offered to bank or government officials, costs in obtaining documenta- tion required, such as land certificates, and so on. Compared to formal services, local informal services generally require very little form-filling or travel. However, the advantage to the borrower of low transaction costs may be more than counterbalanced by their lack of power in setting the terms of a loan, which may be exploitative. Informal services impose their own discipline. The flow of information locally and the small number of providers of informal finance often act as powerful incentives to users to repay loans or save in a disciplined way. A ROSCA member failing to pay their instalment risks social ostracism from neighbours, friends, and relatives; they may be less likely to receive help from these people in times of severe difficulty in future. Poor people are capable of saving The evidence of informal systems disproves the assumption that poor people cannot save. Saving 'in kind' has long been a recognised part of people's livelihood management: saving in cash is a necessity of interaction with the cash economy. Indeed it is often the poorest, who are landless or for other reasons dependent on casual, poorly-paid jobs, who gain a large proportion of their incomes in cash and therefore have most need of savings facilities. The evidence shows that poor people are not only willing to save but at present often pay highly for savings facilities. 24 Informal systems are adaptable. Informal financial services The variety of forms and functions of informal finance demonstrates the adaptability of these systems to different economic conditions and changing circumstances. This contrasts with formal systems which often have to be based on a uniform delivery model. There is thus much to be learned from informal financial systems. Indeed aspects of these systems have found their way into the design of NGO and semi-formal financial services programmes. In particular, both group-based and individual-based schemes have made use of the 'insider knowledge' of other local people: individual-based schemes, such as BRI, through personal references from local representatives, and group- based schemes, such as Grameen, through self-selecting groups of borrowers (see Chapter 1). This brief overview has not identified for whom these services exist - women and men, poor or poorest. The poorest people may find it difficult to save the amount that a ROSCA requires and hence find participation a burden or are excluded. Even if there are a number of people in similar situations, they are often marginalised or isolated and lack the social networks to create their own ROSCA with a lower fee. Indebtedness may also make it difficult for the poorest to save and build up a small asset base - a situation that will be illustrated in the case of low-income and unemployed members of the Ladywood Credit Union in the UK, a case-study scheme described in Chapter 6. There are therefore limitations to the extent to which savings-based user- owned facilities can be of use to very poor people. However, systems that allow flexible amounts to be deposited are more likely to be appropriate. 2.6 Deciding when and how to intervene Before going on to discuss ways of intervening which are useful and relevant to poor people (see Chapter 3), it is necessary to issue some warnings. Several commentators, among them NGO practitioners, have questioned the appropri- ateness of NGOs acting as providers of financial services. Abugre (1992) identifies a range of dangers, and points to the dire consequences of the job being done badly: ⚫ NGOs remain averse to charging positive real interest rates and may, consciously or otherwise, undermine traditional financial systems. ⚫ NGOs do not submit themselves to the discipline required for the provision of sustainable financial services. 25 Microfinance and Poverty Reduction ⚫ Schemes are managed by entirely unprofessional and untrained staff and are often carelessly conceived, designed, and implemented. . There are cases where NGOs have flooded the market with credit, resulting in indebtedness on the part of borrowers, and potentially regressive effects on income and wealth distribution. By extending loans which poor people are unable to pay due to factors beyond their control, or which may have simply been inappropriate in the first place, NGOs can cause a level of indebtedness which may result in the borrower having to liquidate assets in order to repay. Abugre therefore warns against the hasty introduction of new financial services by NGOs and concludes that they should concentrate on what they do well, such as providing social services and acting as confidence brokers in coinmunities. Direct provision may be a risky and problematic strategy for an NGO, particularly as the NGO may not have the range of skills required to develop microfinance interventions, nor experience of the financial skills and respon- sibility required to ensure funds are properly safeguarded and accounted for. A further range of managerial skills are also necessary in managing a portfolio of financial assets such as loans and deposits. NGOS with experience of welfare and relief have more experience of channelling funds than managing them (Bouman, 1995). An NGO must ask itself whether it has the skills to become a banker.. An organisation lacking the relevant skills may consider acquiring them either through recruitment or staff development. Such a strategy itself has important consequences. These skills may be in short supply and recruit- ment prove difficult; they take time to develop and are acquired through experience as well as training. There is often a strong impetus to start work even if the skills of staff are still weak. This can endanger the intervention itself since it is at this early stage that users gain an impression of the nature of the operation, and inexperienced staff are likely to make mistakes. Embarking on direct intervention also raises questions about the long-term sustainability of the service on offer. Financial services should not be provided on a transient or temporary basis. There needs to be a degree of permanence to enable people to plan for their future finan- cial needs. Consideration of the long-term future for a system of finan- cial service provision is therefore important at the outset. Direct provision by an NGO which expects to move away from the area would seldom be appropriate. 26 Informal financial services There is a further range of issues at the level of the macro-economy which should also be considered when deciding whether to intervene. Macro- economic stability is an important pre-requisite for getting a scheme off the ground. Hyper-inflation and economic instability do not encourage individuals to save, and loans under such circumstances are difficult to manage. (However, in Mexico, while formal-sector banks were reeling from massive default caused by the high interest rates and high inflation of 1995, URAC, one of the case-study institutions discussed in Chapter 6, continued to thrive.) Political stability is also needed, since without it there is unlikely to be much confidence in the long-term future of new financial institutions. Before considering scheme design an NGO must also investigate the formal legal regulatory requirements for organisations involved in financial service provision, especially for savings (see Chapter 3). 2.6.1 Research questions on existing informal financial services In carrying out research into the services available, and how they are used, an intervener should try to find answers to a wide range of questions, such as: How do people manage their savings deposits? Are there savings banks, or deposit takers, insurance salesmen, or savings clubs? Do poor people have access to them? If not, how do they save (for example, gold, livestock). Who among the poor uses them (men, women, landless labourers, subsistence farmers etc)? (Extensive use of expensive deposit takers might indicate that the NGO should look first at the reasons why alternatives are not in place: and second at whether there is any possibility for the NGO to get involved, either as promoter or as provider, in savings collection.) How do people temporarily realise the value of assets they hold? Are there pawnbrokers or are there schemes that allow them to pawn land or other major assets (eg jewellery) safely? Who uses these services? (If such devices exist, are they exploitative or enabling? If they are clearly exploitative, there might be a case for an NGO to try to provide or promote an alternative.) How do people get access to the current value of future savings? Are there money-lenders willing to advance small loans against future savings? Are there ROSCAS or managed or commercial chits, or co-operative 2 In a background paper commissioned for the purposes of this book, Shahin Yaqub examined the 'Macroeconomic Conditions for Successful Microfinance for Poor People'. The paper is available from the Policy Department, Oxfam (UK and Ireland). 27 banks? Do poor people have access? Which poor people use them? (If money-lenders appear to be exploiting users, for example by imposing very high interest rates or linking loans to disadvantageous deals over land, labour or commodities, then there might be a case for the NGO to introduce ROSCAS or annual savings clubs, or work as a promoter of self-help groups or credit unions.) How do people make provision for known life-cycle expenses? Do they provide for daughters' marriages, their own old age and funeral, for their heirs? Are there clubs that satisfy these needs, or general savings services or insurance companies that will do as well? Are there government or employer-run schemes? Are there particular expenses for which women have responsibility? How do people cope with emergencies? What happens when a breadwinner is ill, or when a flood or drought occurs? Does the government have schemes that reach poor people in these circumstances? If not, what local provision do people make? How do small-scale entrepreneurs get access to business finance? If so, in what amounts and at what cost? Do women entrepreneurs have access? During the exploratory work done to answer these questions another set of information will come to light-the absolute quantities of cash involved in local financial intermediation. This can be of immense value to scheme designers in cases where a decision is made to intervene. For example, information about amounts repaid regularly to money-lenders will be useful in setting loan sizes and repayment schedules for loan schemes. (Source: Rutherford, 1996.) Much can be learned from the way in which people are already managing their finances. A further aspect is the social relations involved-the groups of people who get together to form ROSCAS, those from whom loans are taken, and those with whom deposits are lodged. Tierney's work on the Oxfam- funded Youth Employment Groups in Tabora Region of Tanzania demon- strates that the design of the intervention, which was based around groups of people with the same occupational background, did not correspond to the pattern of existing financial intermediation, which was organised around small kin-based groups, each including diverse enterprises. Tierney argues that 'the formation of development groups can, ironically, divert people's energy away from improving their lives, because forming the kind of groups which are eligible for financial assistance is a time-consuming activity involving skill 28 Informal financial services in manipulating and maintaining public relations' (Tierneyforthcoming). This illustrates the value of understanding how indigenous financial systems operate, before designing a new microfinance initiative. 2.7 Filling the gaps As well as alerting people to the potential pitfalls of intervention, research to answer the kind of questions suggested above is likely to identify gaps in existing services. There are many ways in which such gaps can be filled and below are some examples of financial service interventions in insurance and hire purchase which can be of use to poor people. For those agencies whose motivation is poverty reduction it is important to link the identification of gaps with a poverty analysis to determine who is excluded from existing services and how such exclusion perpetuates poverty. 2.7.1 Some examples of innovative services Hire-then-purchase for the poor in Bangladesh ACTIONAID found, through the experience of running a group- based lending programme similar to that of the Grameen Bank, that many very poor people were nervous of taking a large loan — the 5,000 taka ($125) needed to buy a rickshaw, for example — in case they were not able to repay it. AA therefore devised a bire-then- purchase scheme for such people. AA bought its own rickshaws and bired them out to group members. A rickshaw driver could hire a rickshaw from AA instead of hiring one from a local 'mohajan'. If he then decided to convert bis contract with AA from hiring to buying, a proportion of the total hiring fees he had already paid was denoted as his down-payment, and be took a regular (smaller) AA loan to pay off the rest. Door-step insurance agents, Cuttack, Orissa In Cuttack, insurance agents from the Peerless company visit house- bolds in low-income areas. They offer simple endowment schemes, which from the point of view of the customers are like accumulating fixed deposit schemes: the customer puts in a fixed amount regularly and then on maturity gets it back plus profits. Life insurance cover is included in the contract. 'Bankassurance: group-based insurance for the rural poor In Bangladesh, one insurance company is pioneering an attempt to match, in the field of insurance, Grameen Bank's success in lending. 29 Delta Life Insurance has been experimenting since 1988 with cut- price basic life-insurance for rural people. Customers are arranged in groups, there is no medical examination and no age-bar, and premiums are tiny and collected weekly. Agents are also involved in Grameen-Bank-style lending and earn an extra commission for the insurance work. In fact the insurance premiums are invested directly in lending (on which healthy interest may be earned). In 1996 Delta was looking for a big NGO partner which could offer the two services- lending and insurance- side by side. Experience so far has shown that demand for such a service is high. Delta is exploring how it can extend this initiative beyond life insurance. 2.8 Promotion: an alternative strategy for NGOS Having identified the gaps in existing financial service provision, an NGO might involve itself in promotion rather than provision. The main alternatives to direct provision of financial services are ones which involve the NGO in a transitional or support role whereby activities such as mobilisation, training, and making links to other organisations are provided. A range of possible approaches are outlined. 2.8.1 Formation of savings groups and development of internal credit facilities Where ROSCAS do not exist or have limited coverage, the NGO might act as a facilitator of their formation or enable them to develop slightly more sophisti- cated systems of internal on-lending which allows savings and loans to take on more flexible formats. This approach has been used by Friends of Women's World Banking in India. In this case the NGO is mainly involved in training and organising the groups. Self-help groups (SHGs) are NGO-led attempts to promote savings clubs, or simple forms of credit union. Those initiated by Friends of Women's World Banking in India are aimed at poor rural women. FWWB (or its partner NGOs) persuades women from the same neigh- bourhood and from similar backgrounds to form small groups of 12 to 15 members. NGO workers encourage the women to meet regularly and frequently and during these meetings the women discuss their financial problems and ways of solving them. The solution they are steered towards involves regular small savings and the immediate conversion of those savings into small loans taken by one or two members at each meeting. Care is taken to Informal financial services involve all group members in the discussion and formulation of rules (how often to meet, the interest to be charged on loans, and repayment arrangements) and then to ensure that every member experiences for herself the activities of saving and of taking and repaying a loan. The group is asked to choose leaders who are trained to manage the group's affairs: if illiteracy or very poor educational levels are a problem then rules are kept deliberately simple (fixed equal savings, and annual dividends rather than monthly interest on savings, for example). These preparations are intended to equip the group for independent survival after the NGO stops sending workers regularly to the meetings. Groups which perform well over several months are able to obtain small bulk loans made by FWWB to the group as a collective. Where there are a number of groups in an area, FWWB may help them form a federation' (apex body') to help with liquidity problems: groups with excess savings deposit them with the federa- tion which on-lends to groups with a strong demand for loans. (Source: WWB, 1993.) However, although this type of intervention can succeed with agency help, it has yet to be proved whether savings and credit groups which are promoted by outsiders can achieve long-term independence (Rutherford, 1996). A range of questions remain: can they save sufficient funds among themselves to satisfy their own demand for loans? Can external funds be introduced into these groups without destroying their independence? 2.8.2 Promotion of small-scale formalised approaches National legislation may allow for credit unions (the World Council of Credit Unions has national and regional affiliates all over the world) or thrift and credit co-operatives (as in Sri Lanka, see 3.4.2). Another approach an NGO might adopt could be the linking up of people interested in establishing such services for themselves with other credit unions or umbrella and apex bodies that are able to promote and advise on particular financial services. Oxfam Hyderabad worked with the Federation of Thrift and Credit Associations in Andhra Pradesh, encouraging exposure visits to flourishing thrift and credit societies by potential members from other areas. The members now have a source of consumption credit based on their own savings. Oxfam Hyderabad saw its support for linking potential groups with an existing thrift and credit structure as a move away from direct funding of NGOs to provide credit. (Source: Oxfam (India) Trust, 1993.) 31 2.8.3 Linking groups to the formal system Existing savings groups or ROSCAS may already have bank savings accounts but are unable to take loans because the bank does not understand their operations or believe them to be creditworthy. The NGO might work with groups to encourage them to build up savings and deposit them in formal institutions. The NGO may then be able to work with a local bank to encour- age it to extend its services to groups. In Ghana, rural banking legislation was designed to create semi- autonomous local banks which would serve people cut off from financial services. However, the banks have experienced a range of problems which led to only 23 out of a total of 123 being classified as operating satisfactorily in 1992 (Onumah, 1995). In 1991 the Garu Bank, a small rural bank set up in 1983 in Ghana, was near to collapse as a result of embezzlement and bad loans. The people of Garu persuaded a member of their own community who was working in Accra to come back to the area and become theman- ager. The Bank is a unit bank and operates relatively autonomously. Share capital of the Bank is owned by the local community, the Catholic Mission, the local Agricultural Station and a Disabled Rehabilitation Centre. Helped by an additional capital injection of $30,000 received from overseas donors via the Catholic Mission the manager trans- formed the situation, and expected to report a profit for the first time. The bank has a range of clients, including local salaried workers such as teachers and government employees. These people are good customers because they take loans which are easily recoverable in the form of deductions made from their salaries at source. Alongside these customers, the Bank provides services to some 300 farmers' groups. Some of these groups were originally formed by the local Agricultural Station and the Catholic Mission and bought shares in the Bank when it was first set up. The manager went to meet the groups to discuss their needs with them. He has developed his own approach to the groups, and stresses that they should be concerned with working together rather than just obtaining credit. He has set up his own criteria for lending to the groups: savings balances of at least 10 per cent of the loan amount; regularity of savings as an indicator of group cohesion; and that the group should have been operating for at least six months. Repayment of the loan on time results in almost automatic qualification for a new loan the following year (although be bad refused loans to a number of groups the previous year due to poor performance). (Source: Abugre, Johnson et al, 1995.)

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

My family loves to eat cereal but there's a lot of unhealthy cereal at supermarkets. When I go shopping for cereal, what do I look for to get healthy cereal?

Cereal is a quick, easy and delicious breakfast option. It can be healthy, too — if you’re filling your cereal bowl from the right box. Many of the eye-catching boxes in the cereal aisle are more sugar bombs than balanced breakfasts, says registered dietitian Beth Czerwony, RD. (Spoiler alert: Funny-shaped marshmallows DO NOT offer much nutritional value.) So, how can you choose a breakfast cereal worthy of spooning for the most important meal of the day? Czerwony has a few suggestions. All the information you need to separate the healthy cereal options from those that are sweet treats in disguise is readily available. All it takes is some nutrition label reading while you’re shopping. “Want to know what cereal is healthy?” asks Czerwony. “The answer is on the side of the box.” Here’s what you want to find: Whole grains supply a healthy foundation for cereals. It doesn’t matter whether it’s whole wheat, whole-grain flour, whole-grain oats or whole-grain brown rice either. “When it comes to nutritional value, whole grains provide quite a payoff,” says Czerwony. Compared to white flour and other refined grains, whole grains are higher in fiber, protein and nutrients, like iron, magnesium, selenium and B vitamins. The reason? Those processed grains lose much of their nutritional value during the milling process. A diet rich in whole grains also can lower your risk of heart disease and help prevent diabetes. (Talk about getting a lot done at breakfast!) Another bonus of whole grain? Fiber, which is fabulous for digestion and your gut health “Fiber slows down digestion so that sugars from what you ate trickle into your bloodstream,” explains Czerwony. “You don’t have those highs and lows, which keeps your body in better balance.” Fiber helps you stay full, too — which means a hearty bowl of fiber-rich cereal for breakfast can help hold you over until lunch and keep your stomach from rumbling during a mid-morning meeting. Pro tip: Aim for at least 3 grams of fiber per serving with cereal. Protein can also help you feel full. While sweet cereals may have only 1 or 2 grams of protein, healthier options can have closer to 10 grams. (Oatmeal can run even higher in the protein count, too, if you count it as a cereal.) Let’s start with this basic fact: Most Americans eat way more than the recommended daily limit on sugar. (In case you’re wondering, the general rule of thumb for daily sugar intake is no more than 36 grams for men and 25 grams for women). To start your day on the right foot, look for lower-sugar cereals with less than 9 grams of sugar per serving. “Keep it in the single digits,” recommends Czerwony. Another good guideline: Don’t pick cereals with sugar listed in the top five ingredients. And beware of “sugar imposters” such as glucose, maltodextrin, high fructose corn syrup and evaporated cane juice. Salt in cereal? You bet — and sweeter cereals are more likely to have elevated sodium levels. “Sweet and salt go together,” says Czerwony. “Manufacturers will add that sodium in to make something sweet taste even sweeter.” Look to choose a cereal with less than 140 milligrams of sodium per serving. Aim for an even lower number if you have high blood pressure (hypertension) or kidney issues. Cereal can be pretty sneaky. Healthy-sounding options like granola, for instance, can pack a surprising amount of fat, sugar and unwanted carbohydrates into those crunchy breakfast nuggets. “A cereal may contain whole grains and be high in fiber and still not be the best choice depending on what else is tossed in there,” cautions Czerwony. “It’s easy to make something unhealthy.” That means it’s up to you to be savvy when looking at the nutrition label and ingredients list. (Want to learn more about reading a nutrition label? Then check out these tips from a registered dietitian.) Your best bet for cereals is to keep your selection plain. “That’s code for skipping flavored and frosted varieties,” says Czerwony. So, you’re going to make a healthy choice and select a basic cereal without magical marshmallows or miniature cookies. The good news? It’s pretty easy to add some excitement to that plain bowl. “A lot of cereals are a neutral when it comes to taste,” notes Czerwony. “That gives you a lot of room to drop in some healthy flavor.” She suggests adding: Fresh fruit. “Topping your cereal with blueberries or some other fresh fruit adds a lot of zing while also being good for you, says Czerwony. (Try to avoid sprinkling in dried fruits, though, as they can be high in sugar.) Nuts. Dropping a few almonds or walnuts on top of your cereal brings crunchy goodness, and nuts are full of health benefits. But watch quantities, as a big pile of nuts can be high in calories. Spices. A dash of cinnamon or another favorite spice can punch up a bowl of cereal. “Spices are great alternatives because they add flavor without adding extra sugar or fats,” says Czerwony. Natural sweeteners. Still craving some sweetness? If so, a drizzle of pure maple syrup or honey may satisfy your sweet tooth. “They’re better for you than refined sugars,” she says. “Moderation is still key, though.”

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== My family loves to eat cereal but there's a lot of unhealthy cereal at supermarkets. When I go shopping for cereal, what do I look for to get healthy cereal? {passage 0} ========== Cereal is a quick, easy and delicious breakfast option. It can be healthy, too — if you’re filling your cereal bowl from the right box. Many of the eye-catching boxes in the cereal aisle are more sugar bombs than balanced breakfasts, says registered dietitian Beth Czerwony, RD. (Spoiler alert: Funny-shaped marshmallows DO NOT offer much nutritional value.) So, how can you choose a breakfast cereal worthy of spooning for the most important meal of the day? Czerwony has a few suggestions. All the information you need to separate the healthy cereal options from those that are sweet treats in disguise is readily available. All it takes is some nutrition label reading while you’re shopping. “Want to know what cereal is healthy?” asks Czerwony. “The answer is on the side of the box.” Here’s what you want to find: Whole grains supply a healthy foundation for cereals. It doesn’t matter whether it’s whole wheat, whole-grain flour, whole-grain oats or whole-grain brown rice either. “When it comes to nutritional value, whole grains provide quite a payoff,” says Czerwony. Compared to white flour and other refined grains, whole grains are higher in fiber, protein and nutrients, like iron, magnesium, selenium and B vitamins. The reason? Those processed grains lose much of their nutritional value during the milling process. A diet rich in whole grains also can lower your risk of heart disease and help prevent diabetes. (Talk about getting a lot done at breakfast!) Another bonus of whole grain? Fiber, which is fabulous for digestion and your gut health “Fiber slows down digestion so that sugars from what you ate trickle into your bloodstream,” explains Czerwony. “You don’t have those highs and lows, which keeps your body in better balance.” Fiber helps you stay full, too — which means a hearty bowl of fiber-rich cereal for breakfast can help hold you over until lunch and keep your stomach from rumbling during a mid-morning meeting. Pro tip: Aim for at least 3 grams of fiber per serving with cereal. Protein can also help you feel full. While sweet cereals may have only 1 or 2 grams of protein, healthier options can have closer to 10 grams. (Oatmeal can run even higher in the protein count, too, if you count it as a cereal.) Let’s start with this basic fact: Most Americans eat way more than the recommended daily limit on sugar. (In case you’re wondering, the general rule of thumb for daily sugar intake is no more than 36 grams for men and 25 grams for women). To start your day on the right foot, look for lower-sugar cereals with less than 9 grams of sugar per serving. “Keep it in the single digits,” recommends Czerwony. Another good guideline: Don’t pick cereals with sugar listed in the top five ingredients. And beware of “sugar imposters” such as glucose, maltodextrin, high fructose corn syrup and evaporated cane juice. Salt in cereal? You bet — and sweeter cereals are more likely to have elevated sodium levels. “Sweet and salt go together,” says Czerwony. “Manufacturers will add that sodium in to make something sweet taste even sweeter.” Look to choose a cereal with less than 140 milligrams of sodium per serving. Aim for an even lower number if you have high blood pressure (hypertension) or kidney issues. Cereal can be pretty sneaky. Healthy-sounding options like granola, for instance, can pack a surprising amount of fat, sugar and unwanted carbohydrates into those crunchy breakfast nuggets. “A cereal may contain whole grains and be high in fiber and still not be the best choice depending on what else is tossed in there,” cautions Czerwony. “It’s easy to make something unhealthy.” That means it’s up to you to be savvy when looking at the nutrition label and ingredients list. (Want to learn more about reading a nutrition label? Then check out these tips from a registered dietitian.) Your best bet for cereals is to keep your selection plain. “That’s code for skipping flavored and frosted varieties,” says Czerwony. So, you’re going to make a healthy choice and select a basic cereal without magical marshmallows or miniature cookies. The good news? It’s pretty easy to add some excitement to that plain bowl. “A lot of cereals are a neutral when it comes to taste,” notes Czerwony. “That gives you a lot of room to drop in some healthy flavor.” She suggests adding: Fresh fruit. “Topping your cereal with blueberries or some other fresh fruit adds a lot of zing while also being good for you, says Czerwony. (Try to avoid sprinkling in dried fruits, though, as they can be high in sugar.) Nuts. Dropping a few almonds or walnuts on top of your cereal brings crunchy goodness, and nuts are full of health benefits. But watch quantities, as a big pile of nuts can be high in calories. Spices. A dash of cinnamon or another favorite spice can punch up a bowl of cereal. “Spices are great alternatives because they add flavor without adding extra sugar or fats,” says Czerwony. Natural sweeteners. Still craving some sweetness? If so, a drizzle of pure maple syrup or honey may satisfy your sweet tooth. “They’re better for you than refined sugars,” she says. “Moderation is still key, though.” https://health.clevelandclinic.org/how-to-pick-a-healthy-cereal

Use only information found in this text to provide your answer.

How many citations are found in this text? List them.

How Much Debt is Outstanding? Gross federal debt is composed of debt held by the public and intragovernmental debt. Debt held by the public—issued through the Bureau of the Fiscal Service—is the total amount the federal government has borrowed from the public and remains outstanding. This measure is generally considered to be the most relevant in macroeconomic terms because it is the amount of debt sold in credit markets. Intragovernmental debt is the amount owed by the federal government to other federal agencies, primarily in the Social Security, Medicare, and Civil Service Retirement and Disability trust funds, to be paid by Treasury.33 The Bureau of the Fiscal Service provides various breakdowns of debt figures. The most up-todate data on federal debt can be found on the “Debt to the Penny” section of the Bureau’s Treasury Direct website.34 The Daily Treasury Statement (DTS) and Monthly Treasury Statement (MTS) provide greater detail on the composition of federal debt, including the operating cash balance, the types of debt sold, the amount of debt subject to the debt limit, and federal tax deposits.35 The Monthly Statement of the Public Debt (MSPD) includes figures from the DTS as well as more detailed information on the types of Treasury securities outstanding.36

TEXT BLOCK: How Much Debt is Outstanding? Gross federal debt is composed of debt held by the public and intragovernmental debt. Debt held by the public—issued through the Bureau of the Fiscal Service—is the total amount the federal government has borrowed from the public and remains outstanding. This measure is generally considered to be the most relevant in macroeconomic terms because it is the amount of debt sold in credit markets. Intragovernmental debt is the amount owed by the federal government to other federal agencies, primarily in the Social Security, Medicare, and Civil Service Retirement and Disability trust funds, to be paid by Treasury.33 The Bureau of the Fiscal Service provides various breakdowns of debt figures. The most up-todate data on federal debt can be found on the “Debt to the Penny” section of the Bureau’s Treasury Direct website.34 The Daily Treasury Statement (DTS) and Monthly Treasury Statement (MTS) provide greater detail on the composition of federal debt, including the operating cash balance, the types of debt sold, the amount of debt subject to the debt limit, and federal tax deposits.35 The Monthly Statement of the Public Debt (MSPD) includes figures from the DTS as well as more detailed information on the types of Treasury securities outstanding.36 SYSTEM INSTRUCTION: Use only information found in this text to provide your answer. QUESTION: How many citations are found in this text? List them.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

In this paper, describe the proposed method about deep reinforcement learning based on LSTM. Explain how the usage of an unlicensed spectrum is optimized by the DRL system.

C. Channel Coding A noticeable feature of the air interface of the 5G is the use of new channel coding techniques: Data channels use lowdensity parity-check (LDPC) codes, and control channels use polar codes [18]. However, the use of these techniques have some limitations. For instance, polar codes can achieve excellent performance, but it takes several iterations to achieve this performance, and there is no way to predict how fast polar codes can reach this desired performance. In addition, LDPC codes suffer from high complexity of decoding when either it is used with large block or the channel is under colored noise. Deep learning is well-known for its high parallelism structure, which can implement one-shot coding/decoding. Thus, many researchers predict that deep learning-based channel coding is a propitious method to enable 5G NR. For instance, the authors of [19] proposed reinforcement learning for effective decoding strategies for binary linear codes such as ReedMuller and BCH codes, and as a case study, they considered bit-flipping decoding. The authors mapped learned bit-flipping decoding to a Markov decision process and reformulated the decoding problem using both standards and fitted Q-learning with a neural network. The neural network architecture consists of two hidden layers with 500 and 1500 neurons with ReLu activation functions. For the training hyperparameters, the authors considered ten iterations and 0.99 as a discount factor. The SNR is ranging from -2dB to 8dB. The authors considered two types of channels, binary symmetric channel, and Additive White Gaussian Noise (AWGN) channel. The authors of [20] proposed three types of deep neural networks for channel decoding for 5G, multi-layer perceptron, convolutional neural network, and recurrent neural network. The authors used polar codes with rate 1/2 and three codeword lengths 8, 16, and 32. The signal to noise ratio is from -2 dB to 20 dB. The authors showed that the recurrent neural network has the best decoding performance but at the cost of high computation time. The authors of [21] studied a low latency, robust, and scalable convolutional neural network-based decoder of convolutional and LPDC codes. The convolution decoder is trained to decode in a single-shot using Mixed-SNR independent sampling. The CNN decoder is tested with different block lengths of 100, 200, and 1000 under the AWGN channel and with total samples of 109 samples, and SNR is ranging from -4dB to 4dB. The proposed model is compared with Viterbi, BiGRY, and bit flipping based decoders using bit error rate and block error rate. The authors showed that CNN outperforms the previously mentioned decoders regarding BER and BLER. Also, CNN decoder is eight times faster than RNN decoders. Another example of deep learning-based channel decoder is proposed in [22]. The proposed deep learning models consists of an iterative belief propagation concatenated with a convolutional neural network (BP-CNN) LDPC decoding under correlated noise, CNN for denoising the received signal and BP for decoding. The authors considered the AWGN channel and BPSK modulation. The authors showed that BPCNN reduces the decoding bit error rate with low complexity. Further studies are required to investigate the performance of deep learning under communication channels which exhibit correlations in fading. Deep learning-based channel coding can achieve a good range of performance–complexity trade-offs, if the training is performed correctly as the choice of code-word length, causes over-fitting and under-fitting. D. Intelligent Radio Resource and Network Management Radio resources are scarce, and there is an increasing demand of wireless traffic. Intelligent wireless network management is the way forward to meet these increasing demands. Machine learning/deep learning can be a promising feature for resource allocation in 5G wireless communication networks. Deep learning can be a good alternative for interference management, spectrum management, multi-path usage, link adaptation, multi-channel access, and traffic congestion. For instance, the authors of [23] proposed an AI scheduler to infer the free slots in a multiple frequencies time division multiple access to avoid congestion and high packet loss. Four last frames state are fed to a neural network, which consists of two fully connected hidden layers. The proposed AI scheduler was tested in a wireless sensor network of 5 nodes and can reduce the collisions with other networks with 50%. The authors of [24] proposed the addition of the artificial intelligence module instead of replacing conventional scheduling module in LTE systems. This AI module can provide conventional scheduling algorithms with the flexibility and speed up the convergence time. As scheduling for cooperative localization is a critical process to elevate the coverage and the localization precision, the authors of [25] presented a deep reinforcement learning for decentralized cooperative localization scheduling in vehicular networks. The authors of [26] proposed a deep reinforcement learning (DRL) based on LSTM to enables small base stations to perform dynamic spectrum access to an unlicensed spectrum. The model enables the dynamic selection of wireless channel, carrier aggregation, and fractional spectrum access. The coexistence of WLAN and other LTE-LAA operators transmitting on the same channel is formulated as a game between the two and each of which aims to maximize its rate while achieving long-term equal-weighted fairness. This game is solved using DRL-LSTM. The proposed framework showed significant improvement. The authors of [27] proposed an AI framework for smart wireless network management based on CNN and RNN to extract both the sequential and spatial features from the raw signals. These features serve as a state of deep reinforcement learning which defines the optimal network policy. The proposed framework was tested using real-experiment an experiment using a real-time heterogeneous wireless network test-bed. The proposed AI framework enhances the average throughput by approximately 36%. However, the proposed framework is costly in terms of training time and memory usage. The authors of [28] proposed a deep-reinforcement learning approach for SDN routing optimization. To evaluate the performance of the proposed DRL based routing model, the scalefree network topology of 14 nodes, and 21 full-duplex links, with uniform link capacities and average node degree of 3, and traffic intensity levels from 12.5% to 125% of the total network capacity. The trained DRL routing model can achieve similar configurations that of methods such as analytical optimization or local-search heuristic methods with minimal delays. Some other work on routing can be found in [29], [30]. Another aspect of network management is interference management. Interference management often relays on algorithms such as WMMSE. This algorithm is costly as it uses matrix inversion, to solve the problem of numerical optimization in signal processing, the authors of [31] proposed to approximate the WMMSE used for interference management, which is has a central role in enabling Massive MIMO systems. The authors showed that SP optimization algorithms could be approximated by a finite-size neural network.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. In this paper, describe the proposed method about deep reinforcement learning based on LSTM. Explain how the usage of an unlicensed spectrum is optimized by the DRL system. C. Channel Coding A noticeable feature of the air interface of the 5G is the use of new channel coding techniques: Data channels use lowdensity parity-check (LDPC) codes, and control channels use polar codes [18]. However, the use of these techniques have some limitations. For instance, polar codes can achieve excellent performance, but it takes several iterations to achieve this performance, and there is no way to predict how fast polar codes can reach this desired performance. In addition, LDPC codes suffer from high complexity of decoding when either it is used with large block or the channel is under colored noise. Deep learning is well-known for its high parallelism structure, which can implement one-shot coding/decoding. Thus, many researchers predict that deep learning-based channel coding is a propitious method to enable 5G NR. For instance, the authors of [19] proposed reinforcement learning for effective decoding strategies for binary linear codes such as ReedMuller and BCH codes, and as a case study, they considered bit-flipping decoding. The authors mapped learned bit-flipping decoding to a Markov decision process and reformulated the decoding problem using both standards and fitted Q-learning with a neural network. The neural network architecture consists of two hidden layers with 500 and 1500 neurons with ReLu activation functions. For the training hyperparameters, the authors considered ten iterations and 0.99 as a discount factor. The SNR is ranging from -2dB to 8dB. The authors considered two types of channels, binary symmetric channel, and Additive White Gaussian Noise (AWGN) channel. The authors of [20] proposed three types of deep neural networks for channel decoding for 5G, multi-layer perceptron, convolutional neural network, and recurrent neural network. The authors used polar codes with rate 1/2 and three codeword lengths 8, 16, and 32. The signal to noise ratio is from -2 dB to 20 dB. The authors showed that the recurrent neural network has the best decoding performance but at the cost of high computation time. The authors of [21] studied a low latency, robust, and scalable convolutional neural network-based decoder of convolutional and LPDC codes. The convolution decoder is trained to decode in a single-shot using Mixed-SNR independent sampling. The CNN decoder is tested with different block lengths of 100, 200, and 1000 under the AWGN channel and with total samples of 109 samples, and SNR is ranging from -4dB to 4dB. The proposed model is compared with Viterbi, BiGRY, and bit flipping based decoders using bit error rate and block error rate. The authors showed that CNN outperforms the previously mentioned decoders regarding BER and BLER. Also, CNN decoder is eight times faster than RNN decoders. Another example of deep learning-based channel decoder is proposed in [22]. The proposed deep learning models consists of an iterative belief propagation concatenated with a convolutional neural network (BP-CNN) LDPC decoding under correlated noise, CNN for denoising the received signal and BP for decoding. The authors considered the AWGN channel and BPSK modulation. The authors showed that BPCNN reduces the decoding bit error rate with low complexity. Further studies are required to investigate the performance of deep learning under communication channels which exhibit correlations in fading. Deep learning-based channel coding can achieve a good range of performance–complexity trade-offs, if the training is performed correctly as the choice of code-word length, causes over-fitting and under-fitting. D. Intelligent Radio Resource and Network Management Radio resources are scarce, and there is an increasing demand of wireless traffic. Intelligent wireless network management is the way forward to meet these increasing demands. Machine learning/deep learning can be a promising feature for resource allocation in 5G wireless communication networks. Deep learning can be a good alternative for interference management, spectrum management, multi-path usage, link adaptation, multi-channel access, and traffic congestion. For instance, the authors of [23] proposed an AI scheduler to infer the free slots in a multiple frequencies time division multiple access to avoid congestion and high packet loss. Four last frames state are fed to a neural network, which consists of two fully connected hidden layers. The proposed AI scheduler was tested in a wireless sensor network of 5 nodes and can reduce the collisions with other networks with 50%. The authors of [24] proposed the addition of the artificial intelligence module instead of replacing conventional scheduling module in LTE systems. This AI module can provide conventional scheduling algorithms with the flexibility and speed up the convergence time. As scheduling for cooperative localization is a critical process to elevate the coverage and the localization precision, the authors of [25] presented a deep reinforcement learning for decentralized cooperative localization scheduling in vehicular networks. The authors of [26] proposed a deep reinforcement learning (DRL) based on LSTM to enables small base stations to perform dynamic spectrum access to an unlicensed spectrum. The model enables the dynamic selection of wireless channel, carrier aggregation, and fractional spectrum access. The coexistence of WLAN and other LTE-LAA operators transmitting on the same channel is formulated as a game between the two and each of which aims to maximize its rate while achieving long-term equal-weighted fairness. This game is solved using DRL-LSTM. The proposed framework showed significant improvement. The authors of [27] proposed an AI framework for smart wireless network management based on CNN and RNN to extract both the sequential and spatial features from the raw signals. These features serve as a state of deep reinforcement learning which defines the optimal network policy. The proposed framework was tested using real-experiment an experiment using a real-time heterogeneous wireless network test-bed. The proposed AI framework enhances the average throughput by approximately 36%. However, the proposed framework is costly in terms of training time and memory usage. The authors of [28] proposed a deep-reinforcement learning approach for SDN routing optimization. To evaluate the performance of the proposed DRL based routing model, the scalefree network topology of 14 nodes, and 21 full-duplex links, with uniform link capacities and average node degree of 3, and traffic intensity levels from 12.5% to 125% of the total network capacity. The trained DRL routing model can achieve similar configurations that of methods such as analytical optimization or local-search heuristic methods with minimal delays. Some other work on routing can be found in [29], [30]. Another aspect of network management is interference management. Interference management often relays on algorithms such as WMMSE. This algorithm is costly as it uses matrix inversion, to solve the problem of numerical optimization in signal processing, the authors of [31] proposed to approximate the WMMSE used for interference management, which is has a central role in enabling Massive MIMO systems. The authors showed that SP optimization algorithms could be approximated by a finite-size neural network. https://arxiv.org/pdf/2009.04943

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

What is SpaceX about? What are its achievements, missions, and prospects if any mentioned? Summarize all these in a bulleted list of about 500 words.

SpaceX, American aerospace company founded in 2002 that helped usher in the era of commercial spaceflight. It was the first private company to successfully launch and return a spacecraft from Earth orbit and the first to launch a crewed spacecraft and dock it with the International Space Station (ISS). Headquarters are in Hawthorne, California. SpaceX was formed by entrepreneur Elon Musk in the hopes of revolutionizing the aerospace industry and making affordable spaceflight a reality. The company entered the arena with the Falcon 1 rocket, a two-stage liquid-fueled craft designed to send small satellites into orbit. The Falcon 1 was vastly cheaper to build and operate than its competitors, a field largely populated by spacecraft built by publicly owned and government-funded companies such as Lockheed Martin and Boeing. Part of the rocket’s cost-effectiveness was made possible by the SpaceX-developed Merlin engine, a cheaper alternative to those used by other companies. SpaceX also focused on making reusable rockets (other launch vehicles are generally made for one-time use). Falcon 1 rocketLaunch of a Falcon 1 rocket from the SpaceX launch site on Kwajalein Atoll, Marshall Islands, September 28, 2008. Dragon on recovery shipThe SpaceX Dragon spacecraft secured aboard the deck of a recovery ship after its first successful orbital flight, December 8, 2010. In March 2006 SpaceX made its first Falcon 1 launch, which began successfully but ended prematurely because of a fuel leak and fire. By this time, however, the company had already earned millions of dollars in launching orders, many of them from the U.S. government. In August of that year SpaceX was a winner of a NASA competition for funds to build and demonstrate spacecraft that could potentially service the ISS after the decommissioning of the space shuttle. Falcon 1 launches that failed to attain Earth orbit followed in March 2007 and August 2008, but in September 2008 SpaceX became the first privately owned company to send a liquid-fueled rocket into orbit. Three months later it won a NASA contract for servicing the ISS that was worth more than $1 billion. Witness the launch of the SpaceX Dragon capsule, May 25, 2012 Witness the launch of the SpaceX Dragon capsule, May 25, 2012Video released by spacecraft maker SpaceX celebrating its Dragon capsule, which on May 25, 2012, became the first commercial spacecraft to dock with the International Space Station. See all videos for this article Learn about SpaceX, the first private company in history to send a spacecraft, which it named Dragon, to the International Space Station Learn about SpaceX, the first private company in history to send a spacecraft, which it named Dragon, to the International Space StationVideo released by the spacecraft maker SpaceX in August 2012 after it won a contract with NASA to prepare its Dragon spacecraft to carry astronauts into space. See all videos for this article In 2010 SpaceX first launched its Falcon 9, a bigger craft so named for its use of nine engines, and the following year it broke ground on a launch site for the Falcon Heavy, a craft the company hoped would be the first to break the $1,000-per-pound-to-orbit cost barrier and that might one day be used to transport astronauts into deep space. In December 2010 the company reached another milestone, becoming the first commercial company to release a spacecraft—the Dragon capsule—into orbit and successfully return it to Earth. Dragon again made history on May 25, 2012, when it became the first commercial spacecraft to dock with the ISS, to which it successfully delivered cargo. In August that year, SpaceX announced that it had won a contract from NASA to develop a successor to the space shuttle that would transport astronauts into space. Falcon 9 first-stage landingThe landing of a Falcon 9 first stage at Cape Canaveral, Florida, December 21, 2015. This was the first time a rocket stage launched a spacecraft into orbit and then returned to a landing on Earth. SpaceX: Falcon Heavy rocketLaunch of the SpaceX Falcon Heavy rocket from the Kennedy Space Center, Cape Canaveral, Florida, February 6, 2018. The Falcon 9 was designed so that its first stage could be reused. In 2015 a Falcon 9 first stage successfully returned to Earth near its launch site. Beginning in 2016, SpaceX also began using drone ships for rocket stage landings. A rocket stage that had returned to Earth was successfully reused in a 2017 launch. That same year, a Dragon capsule was reused on a flight to the ISS. The Falcon Heavy rocket had its first test flight in 2018. Two of the three first stages landed successfully; the third hit the water near the drone ship. That Falcon Heavy did not carry a satellite but instead placed into orbit around the Sun a Tesla Roadster with a mannequin in a space suit buckled into the driver’s seat. The first operational flight of the Falcon Heavy launched on April 11, 2019. In 2019 SpaceX began launching satellites for its Starlink megaconstellation, which provides satellite Internet service. About 50 Starlink satellites are launched at a time on a Falcon 9 flight. As of 2023, Starlink had 3,660 active satellites, half of all active satellites in orbit. A further 7,500 satellites have been approved by the U.S. Federal Communications Commission, and SpaceX ultimately seeks to have 29,988 satellites orbiting between 340 and 614 km (211 and 381 miles) above Earth. The first crewed flight of a Dragon capsule to the ISS launched on May 30, 2020, with astronauts Doug Hurley and Robert Behnken. SpaceX also announced the successor to the Falcon 9 and the Falcon Heavy: the Super Heavy–Starship system (originally called the BFR [Big Falcon Rocket]). The Super Heavy first stage would be capable of lifting 100,000 kg (220,000 pounds) to low Earth orbit. The payload would be the Starship, a spacecraft designed for several purposes, including providing fast transportation between cities on Earth and building bases on the Moon and Mars. SpaceX planned to use the Starship for a flight around the Moon carrying Japanese businessman Maezawa Yusaku and several artists in 2023, for flights to land astronauts on the Moon as part of NASA’s Artemis program, and eventually to launch settlers to Mars.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== What is SpaceX about? What are its achievements, missions, and prospects if any mentioned? Summarize all these in a bulleted list of about 500 words. {passage 0} ========== SpaceX, American aerospace company founded in 2002 that helped usher in the era of commercial spaceflight. It was the first private company to successfully launch and return a spacecraft from Earth orbit and the first to launch a crewed spacecraft and dock it with the International Space Station (ISS). Headquarters are in Hawthorne, California. SpaceX was formed by entrepreneur Elon Musk in the hopes of revolutionizing the aerospace industry and making affordable spaceflight a reality. The company entered the arena with the Falcon 1 rocket, a two-stage liquid-fueled craft designed to send small satellites into orbit. The Falcon 1 was vastly cheaper to build and operate than its competitors, a field largely populated by spacecraft built by publicly owned and government-funded companies such as Lockheed Martin and Boeing. Part of the rocket’s cost-effectiveness was made possible by the SpaceX-developed Merlin engine, a cheaper alternative to those used by other companies. SpaceX also focused on making reusable rockets (other launch vehicles are generally made for one-time use). Falcon 1 rocketLaunch of a Falcon 1 rocket from the SpaceX launch site on Kwajalein Atoll, Marshall Islands, September 28, 2008. Dragon on recovery shipThe SpaceX Dragon spacecraft secured aboard the deck of a recovery ship after its first successful orbital flight, December 8, 2010. In March 2006 SpaceX made its first Falcon 1 launch, which began successfully but ended prematurely because of a fuel leak and fire. By this time, however, the company had already earned millions of dollars in launching orders, many of them from the U.S. government. In August of that year SpaceX was a winner of a NASA competition for funds to build and demonstrate spacecraft that could potentially service the ISS after the decommissioning of the space shuttle. Falcon 1 launches that failed to attain Earth orbit followed in March 2007 and August 2008, but in September 2008 SpaceX became the first privately owned company to send a liquid-fueled rocket into orbit. Three months later it won a NASA contract for servicing the ISS that was worth more than $1 billion. Witness the launch of the SpaceX Dragon capsule, May 25, 2012 Witness the launch of the SpaceX Dragon capsule, May 25, 2012Video released by spacecraft maker SpaceX celebrating its Dragon capsule, which on May 25, 2012, became the first commercial spacecraft to dock with the International Space Station. See all videos for this article Learn about SpaceX, the first private company in history to send a spacecraft, which it named Dragon, to the International Space Station Learn about SpaceX, the first private company in history to send a spacecraft, which it named Dragon, to the International Space StationVideo released by the spacecraft maker SpaceX in August 2012 after it won a contract with NASA to prepare its Dragon spacecraft to carry astronauts into space. See all videos for this article In 2010 SpaceX first launched its Falcon 9, a bigger craft so named for its use of nine engines, and the following year it broke ground on a launch site for the Falcon Heavy, a craft the company hoped would be the first to break the $1,000-per-pound-to-orbit cost barrier and that might one day be used to transport astronauts into deep space. In December 2010 the company reached another milestone, becoming the first commercial company to release a spacecraft—the Dragon capsule—into orbit and successfully return it to Earth. Dragon again made history on May 25, 2012, when it became the first commercial spacecraft to dock with the ISS, to which it successfully delivered cargo. In August that year, SpaceX announced that it had won a contract from NASA to develop a successor to the space shuttle that would transport astronauts into space. Falcon 9 first-stage landingThe landing of a Falcon 9 first stage at Cape Canaveral, Florida, December 21, 2015. This was the first time a rocket stage launched a spacecraft into orbit and then returned to a landing on Earth. SpaceX: Falcon Heavy rocketLaunch of the SpaceX Falcon Heavy rocket from the Kennedy Space Center, Cape Canaveral, Florida, February 6, 2018. The Falcon 9 was designed so that its first stage could be reused. In 2015 a Falcon 9 first stage successfully returned to Earth near its launch site. Beginning in 2016, SpaceX also began using drone ships for rocket stage landings. A rocket stage that had returned to Earth was successfully reused in a 2017 launch. That same year, a Dragon capsule was reused on a flight to the ISS. The Falcon Heavy rocket had its first test flight in 2018. Two of the three first stages landed successfully; the third hit the water near the drone ship. That Falcon Heavy did not carry a satellite but instead placed into orbit around the Sun a Tesla Roadster with a mannequin in a space suit buckled into the driver’s seat. The first operational flight of the Falcon Heavy launched on April 11, 2019. In 2019 SpaceX began launching satellites for its Starlink megaconstellation, which provides satellite Internet service. About 50 Starlink satellites are launched at a time on a Falcon 9 flight. As of 2023, Starlink had 3,660 active satellites, half of all active satellites in orbit. A further 7,500 satellites have been approved by the U.S. Federal Communications Commission, and SpaceX ultimately seeks to have 29,988 satellites orbiting between 340 and 614 km (211 and 381 miles) above Earth. The first crewed flight of a Dragon capsule to the ISS launched on May 30, 2020, with astronauts Doug Hurley and Robert Behnken. SpaceX also announced the successor to the Falcon 9 and the Falcon Heavy: the Super Heavy–Starship system (originally called the BFR [Big Falcon Rocket]). The Super Heavy first stage would be capable of lifting 100,000 kg (220,000 pounds) to low Earth orbit. The payload would be the Starship, a spacecraft designed for several purposes, including providing fast transportation between cities on Earth and building bases on the Moon and Mars. SpaceX planned to use the Starship for a flight around the Moon carrying Japanese businessman Maezawa Yusaku and several artists in 2023, for flights to land astronauts on the Moon as part of NASA’s Artemis program, and eventually to launch settlers to Mars. https://www.britannica.com/topic/SpaceX

You can only answer a prompt using the information contained in the prompt context, you cannot rely on your own knowledge or outside knowledge to answer, only what is shown in the literal text of the prompt.

Please summarise what the Animal Welfare Act is and what/who is affected by this act.

In 1966, Congress passed legislation that later became known as the Animal Welfare Act (P.L. 89-544) with goals of preventing the theft and sale of pets to research laboratories and regulating the humane care and handling of dogs, cats, and other laboratory animals. The Animal Welfare Act as amended (AWA, 7 U.S.C. §§2131-2156) is the central federal statute governing the humane care and handling of mammals and certain other animals. Since its enactment, Congress has amended the law to expand the types of animals it covers and activities it regulates and to clarify various provisions. These amendments have strengthened enforcement, expanded coverage to more animals and activities, and curtailed cruel practices (e.g., animal fighting), among other things. The AWA covers any live or dead warm-blooded animal, as defined, determined by the U.S. Department of Agriculture (USDA) to be used for research, exhibition, or as a pet. In addition, the AWA addresses animal fighting and the importation of certain dogs into the United States. The AWA’s statutory definition of animal excludes birds, rats, and mice bred for research; horses not used for research; and other farm animals used in the production of food and fiber. The act applies to animal dealers (e.g., pet breeders, medical research suppliers), exhibitors (e.g., zoos, circuses), research facilities (e.g., private and federal laboratories that use animals in research), and transporters (e.g., airlines, railroads, truckers). Covered entities must meet certain standards described in law and regulation and keep certain records. The AWA establishes penalties for noncompliance. USDA’s Animal and Plant Health Inspection Service (APHIS) administers the AWA. In carrying out this responsibility, APHIS promulgates and updates AWA regulations; licenses and registers entities subject to the AWA; inspects the premises of licensed and registered entities; investigates potential violations; and enforces AWA provisions. Animal welfare issues generate significant attention from stakeholder groups. For example, animal welfare advocates have called on Congress to define specific standards for animal care within AWA legislation, increase AWA enforcement, and expand AWA coverage to even more covered animals, entities, and activities. Other stakeholders, including entities regulated under the AWA, have called on Congress to streamline USDA’s AWA oversight and enforcement. Additional issues debated in recent years include the role and care of research animals and federal oversight of pet breeding operations, circuses, and animal shelters.

You can only answer a prompt using the information contained in the prompt context, you cannot rely on your own knowledge or outside knowledge to answer, only what is shown in the literal text of the prompt. In 1966, Congress passed legislation that later became known as the Animal Welfare Act (P.L. 89-544) with goals of preventing the theft and sale of pets to research laboratories and regulating the humane care and handling of dogs, cats, and other laboratory animals. The Animal Welfare Act as amended (AWA, 7 U.S.C. §§2131-2156) is the central federal statute governing the humane care and handling of mammals and certain other animals. Since its enactment, Congress has amended the law to expand the types of animals it covers and activities it regulates and to clarify various provisions. These amendments have strengthened enforcement, expanded coverage to more animals and activities, and curtailed cruel practices (e.g., animal fighting), among other things. The AWA covers any live or dead warm-blooded animal, as defined, determined by the U.S. Department of Agriculture (USDA) to be used for research, exhibition, or as a pet. In addition, the AWA addresses animal fighting and the importation of certain dogs into the United States. The AWA’s statutory definition of animal excludes birds, rats, and mice bred for research; horses not used for research; and other farm animals used in the production of food and fiber. The act applies to animal dealers (e.g., pet breeders, medical research suppliers), exhibitors (e.g., zoos, circuses), research facilities (e.g., private and federal laboratories that use animals in research), and transporters (e.g., airlines, railroads, truckers). Covered entities must meet certain standards described in law and regulation and keep certain records. The AWA establishes penalties for noncompliance. USDA’s Animal and Plant Health Inspection Service (APHIS) administers the AWA. In carrying out this responsibility, APHIS promulgates and updates AWA regulations; licenses and registers entities subject to the AWA; inspects the premises of licensed and registered entities; investigates potential violations; and enforces AWA provisions. Animal welfare issues generate significant attention from stakeholder groups. For example, animal welfare advocates have called on Congress to define specific standards for animal care within AWA legislation, increase AWA enforcement, and expand AWA coverage to even more covered animals, entities, and activities. Other stakeholders, including entities regulated under the AWA, have called on Congress to streamline USDA’s AWA oversight and enforcement. Additional issues debated in recent years include the role and care of research animals and federal oversight of pet breeding operations, circuses, and animal shelters. Please summarise what the Animal Welfare Act is and what/who is affected by this act.

Use the info in this document and not any other source.

Categorize the terms into "Device", "Procedure", and "Other", and exclude any financial or insurance related terms.

N Non-covered charges: Costs for dental care your insurer does not cover. In some cases the service is a covered service, but the insurer is not responsible for the entire charge. In these cases, you will be responsible for any charge not covered by your dental plan. You may wish to call your insurer or consult your dental plan or dental policy to determine whether certain services are included in your plan before you receive those services from your dentist. Non-Covered Services: Dental services not listed as a benefit. If you receive non-covered services, your dental plan will not pay for them. Your provider will bill you. You will be responsible for the full cost. Usually payments count toward deductible. Check with your insurer. Make sure you know what services are covered before you see your dentist. Nonduplication of Benefits: Occurs when you have two insurance plans. It’s how our second insurance carrier calculates its payment. The secondary carrier calculates what it would have paid if it were your primary plan. Then it subtracts what the other plan paid. Examples: Your primary carrier paid 80 percent. Your secondary carrier normally covers 80 percent. Your secondary carrier would not make any additional payment. If the primary carrier paid 50 percent. The secondary carrier would pay up to 30 percent. O Occlusion: Any contact between biting or chewing surfaces of upper and lower teeth. Occlusal Guard: A removable device worn between the upper and lower teeth to prevent clenching or grinding. [NOTE: ODONTOPLASTY WAS REMOVED] Open Enrollment/Open Enrollment Period: Time of year when an eligible person may add, change or terminate a dental plan or dental policy for the next contract year. Open Panel: Allows you to receive care from any dentist. It allows any dentist to participate. Any dentist may accept or refuse to treat patients enrolled in the plan. Open panel plans often are described as freedom of choice plans. Orthodontic Retainer: Appliance to stabilize teeth following orthodontic treatment. Glossary of Dental Insurance and Dental Care Terms 12 * American Dental Association Current Dental Terminology 2011-2012, glossary. **Dental Benefits: A Guide to Dental PPOs, HMOs And Other Managed Plans, Don Mayes, Revised Edition, 2002. **FDA/ADA radiograph guidelines. National Association of Dental Plans, www.nadp.org Orthodontics and dentofacial orthopedics: Branch of dentistry. Includes the diagnosis, prevention, interception, and correction of malocclusion. Also includes neuromuscular and skeletal abnormalities of the developing or mature orofacial structures. Orthodontist: Specialist who treats malocclusion and other neuromuscular and skeletal abnormalities of the teeth and their surrounding structures. Orthotic device: Dental appliance used to support, align, prevent or correct deformities, or to improve the function of the oral Out-of-Network: Care from providers not on your plan. This includes dentists and clinics. Usually, you will pay more out of your own pocket when you receive dental care out-of-network providers. Out-of-network benefits: Coverage for services from providers who are not under a contract with your dental plan. Out-of-pocket cost: The amount plan members must pay for care. Includes the difference between the amount charged by a provider and what a health plan pays for such services. Out-of-Pocket Maximum: The most a dental plan requires a member to pay in a year. Deductibles, co-payments and co-insurance count toward the out-of-pocket maximum. The only dental benefits that have out-of-pocket maximums are child benefits purchased through public exchanges, or purchased as an individual or through a small group. The out-of-pocket maximum for one child is $350 and for more than one child is $700 in all states. After reaching an out-of-pocket maximum, the plan pays 100% of the cost of pediatric dental services. This only applies to covered services. Members are still responsible for services that are not covered by the plan. Members also continue to pay their monthly premiums. Overbilling: Stating fees as higher than actual charges. Example: when you are charged one fee and an insurance company is billed a higher fee. This is done to use your co-payment. It also done to increase your fees solely because you are covered under a dental benefits plan. Overdenture: See Denture/Overdenture. P Palate: The hard and soft tissues forming the roof of the mouth. It separates the oral and nasal cavities. Palliative: Treatment that relieves pain but may not remove the cause of the pain. Partial Denture: See Denture/Partial Denture. Glossary of Dental Insurance and Dental Care Terms 13 * American Dental Association Current Dental Terminology 2011-2012, glossary. **Dental Benefits: A Guide to Dental PPOs, HMOs And Other Managed Plans, Don Mayes, Revised Edition, 2002. **FDA/ADA radiograph guidelines. National Association of Dental Plans, www.nadp.org Participating Provider: Dentists and other licensed dental providers on your plan. They have a contract with your plan. The contract includes set service fees. Payer: Party responsible for paying your claims. It can be a self-insured employer, insurance company or governmental agency. Pediatric dentist: A dental specialist. Treats children from birth through adolescence. Provides primary and comprehensive preventive and therapeutic oral health care. Formerly known as a pedodontist. Periodontal: Branch of dentistry that involves the prevention and treatment of gum disease. Periodontal disease: Inflammation process of gums and/or periodontal membrane of the teeth. Results in an abnormally deep gingival sulcus. Possibly produces periodontal pockets and loss of supporting alveolar bone. Periodontist: A dental specialist. Treats diseases of the supporting and surrounding tissues of the teeth. Periodontitis: Inflammation and loss of the connective tissue of the supporting or surrounding structure of teeth. With loss of attachment. [NOTE: PIN REMOVED] Plan Year: See Benefit Year. Plaque: A soft sticky substance. Composed largely of bacteria and bacterial derivatives. It forms on teeth daily. Point of Service (POS) Plan: A dental plan that allows you to choose at the time of dental service whether you will go to a provider within your dental plan's network or get dental care from a provider outside the network. [NOTE: PORCELAIN/CERAMIC REMOVED] [NOTE: POST REMOVED] Preauthorization: A process that your dental plan or insurer uses to make a decision that particular dental services are covered. Your plan may require preauthorization for certain services, such as crowns, before you receive them. Preauthorization requirements are generally waived if you need emergency care. Sometimes called prior authorization. [NOTE: PRECERTIFICATION REMOVED] Predetermination: A process where a dentist submits a treatment plan to the payer before treatment begins. The payer reviews the treatment plan. The payer notifies you and your dentist about one or more of the following: your eligibility, covered services, amounts payable, co-payment and deductibles and plan maximums. See preauthorization. Glossary of Dental Insurance and Dental Care Terms 14 * American Dental Association Current Dental Terminology 2011-2012, glossary. **Dental Benefits: A Guide to Dental PPOs, HMOs And Other Managed Plans, Don Mayes, Revised Edition, 2002. **FDA/ADA radiograph guidelines. National Association of Dental Plans, www.nadp.org Pre-existing condition: A dental condition that exists for a set time prior to enrollment in a dental plan, regardless of whether the condition has been formally diagnosed. The only pre-existing condition that is common for dental plans or policies is a missing tooth. [REMOVED PRECIOUS OR HIGH NOBLE METALS – SEE METALS, CLASSIFICATIONS –ACCORDING TO CDT] Pretreatement Estimate: See predetermination. ** Preferred Provider Organization (PPO): See DPPO. Premedication: The use of medications prior to dental procedures. Prepaid dental plan: A method of funding dental care costs in advance of services. For a defined population. Premium: The amount you pay to a dental insurance company for dental coverage. The dental insurance company generally recalculates the premium each policy year. This amount is usually paid in monthly installments. When you receive dental insurance through an employer, the employer may pay a portion of the premium and you pay the rest, often through payroll deductions. Preventive Services: See diagnostic and preventive services. Primary dentition: Another name for baby teeth. See deciduous. Primary payer: The third party payer with first responsibility in a benefit determination. Prophylaxis: Scaling and polishing procedure. Performed to remove coronal plaque, calculus and stains. ** Prosthodontic: Branch of dentistry that deals with the repair of teeth by crowns, inlays or onlays and/or the replacement of missing teeth and related mouth or jaw structures by bridges, dentures, implants or other artificial devises. Prosthodontist: A dental specialist. Restores natural teeth. Replaces missing teeth with artificial substitutes. Provider: A dentist or other dental care professional, or clinic that is accredited, licensed or certified to provide dental services in their state, and is providing services within the scope of that accreditation, license or certification. Provider network: Dentists and other dental care professionals who agree to provide dental care to members of a dental plan, under the terms of a contract.

N Non-covered charges: Costs for dental care your insurer does not cover. In some cases the service is a covered service, but the insurer is not responsible for the entire charge. In these cases, you will be responsible for any charge not covered by your dental plan. You may wish to call your insurer or consult your dental plan or dental policy to determine whether certain services are included in your plan before you receive those services from your dentist. Non-Covered Services: Dental services not listed as a benefit. If you receive non-covered services, your dental plan will not pay for them. Your provider will bill you. You will be responsible for the full cost. Usually payments count toward deductible. Check with your insurer. Make sure you know what services are covered before you see your dentist. Nonduplication of Benefits: Occurs when you have two insurance plans. It’s how our second insurance carrier calculates its payment. The secondary carrier calculates what it would have paid if it were your primary plan. Then it subtracts what the other plan paid. Examples: Your primary carrier paid 80 percent. Your secondary carrier normally covers 80 percent. Your secondary carrier would not make any additional payment. If the primary carrier paid 50 percent. The secondary carrier would pay up to 30 percent. O Occlusion: Any contact between biting or chewing surfaces of upper and lower teeth. Occlusal Guard: A removable device worn between the upper and lower teeth to prevent clenching or grinding. [NOTE: ODONTOPLASTY WAS REMOVED] Open Enrollment/Open Enrollment Period: Time of year when an eligible person may add, change or terminate a dental plan or dental policy for the next contract year. Open Panel: Allows you to receive care from any dentist. It allows any dentist to participate. Any dentist may accept or refuse to treat patients enrolled in the plan. Open panel plans often are described as freedom of choice plans. Orthodontic Retainer: Appliance to stabilize teeth following orthodontic treatment. Glossary of Dental Insurance and Dental Care Terms 12 * American Dental Association Current Dental Terminology 2011-2012, glossary. **Dental Benefits: A Guide to Dental PPOs, HMOs And Other Managed Plans, Don Mayes, Revised Edition, 2002. **FDA/ADA radiograph guidelines. National Association of Dental Plans, www.nadp.org Orthodontics and dentofacial orthopedics: Branch of dentistry. Includes the diagnosis, prevention, interception, and correction of malocclusion. Also includes neuromuscular and skeletal abnormalities of the developing or mature orofacial structures. Orthodontist: Specialist who treats malocclusion and other neuromuscular and skeletal abnormalities of the teeth and their surrounding structures. Orthotic device: Dental appliance used to support, align, prevent or correct deformities, or to improve the function of the oral Out-of-Network: Care from providers not on your plan. This includes dentists and clinics. Usually, you will pay more out of your own pocket when you receive dental care out-of-network providers. Out-of-network benefits: Coverage for services from providers who are not under a contract with your dental plan. Out-of-pocket cost: The amount plan members must pay for care. Includes the difference between the amount charged by a provider and what a health plan pays for such services. Out-of-Pocket Maximum: The most a dental plan requires a member to pay in a year. Deductibles, co-payments and co-insurance count toward the out-of-pocket maximum. The only dental benefits that have out-of-pocket maximums are child benefits purchased through public exchanges, or purchased as an individual or through a small group. The out-of-pocket maximum for one child is $350 and for more than one child is $700 in all states. After reaching an out-of-pocket maximum, the plan pays 100% of the cost of pediatric dental services. This only applies to covered services. Members are still responsible for services that are not covered by the plan. Members also continue to pay their monthly premiums. Overbilling: Stating fees as higher than actual charges. Example: when you are charged one fee and an insurance company is billed a higher fee. This is done to use your co-payment. It also done to increase your fees solely because you are covered under a dental benefits plan. Overdenture: See Denture/Overdenture. P Palate: The hard and soft tissues forming the roof of the mouth. It separates the oral and nasal cavities. Palliative: Treatment that relieves pain but may not remove the cause of the pain. Partial Denture: See Denture/Partial Denture. Glossary of Dental Insurance and Dental Care Terms 13 * American Dental Association Current Dental Terminology 2011-2012, glossary. **Dental Benefits: A Guide to Dental PPOs, HMOs And Other Managed Plans, Don Mayes, Revised Edition, 2002. **FDA/ADA radiograph guidelines. National Association of Dental Plans, www.nadp.org Participating Provider: Dentists and other licensed dental providers on your plan. They have a contract with your plan. The contract includes set service fees. Payer: Party responsible for paying your claims. It can be a self-insured employer, insurance company or governmental agency. Pediatric dentist: A dental specialist. Treats children from birth through adolescence. Provides primary and comprehensive preventive and therapeutic oral health care. Formerly known as a pedodontist. Periodontal: Branch of dentistry that involves the prevention and treatment of gum disease. Periodontal disease: Inflammation process of gums and/or periodontal membrane of the teeth. Results in an abnormally deep gingival sulcus. Possibly produces periodontal pockets and loss of supporting alveolar bone. Periodontist: A dental specialist. Treats diseases of the supporting and surrounding tissues of the teeth. Periodontitis: Inflammation and loss of the connective tissue of the supporting or surrounding structure of teeth. With loss of attachment. [NOTE: PIN REMOVED] Plan Year: See Benefit Year. Plaque: A soft sticky substance. Composed largely of bacteria and bacterial derivatives. It forms on teeth daily. Point of Service (POS) Plan: A dental plan that allows you to choose at the time of dental service whether you will go to a provider within your dental plan's network or get dental care from a provider outside the network. [NOTE: PORCELAIN/CERAMIC REMOVED] [NOTE: POST REMOVED] Preauthorization: A process that your dental plan or insurer uses to make a decision that particular dental services are covered. Your plan may require preauthorization for certain services, such as crowns, before you receive them. Preauthorization requirements are generally waived if you need emergency care. Sometimes called prior authorization. [NOTE: PRECERTIFICATION REMOVED] Predetermination: A process where a dentist submits a treatment plan to the payer before treatment begins. The payer reviews the treatment plan. The payer notifies you and your dentist about one or more of the following: your eligibility, covered services, amounts payable, co-payment and deductibles and plan maximums. See preauthorization. Glossary of Dental Insurance and Dental Care Terms 14 * American Dental Association Current Dental Terminology 2011-2012, glossary. **Dental Benefits: A Guide to Dental PPOs, HMOs And Other Managed Plans, Don Mayes, Revised Edition, 2002. **FDA/ADA radiograph guidelines. National Association of Dental Plans, www.nadp.org Pre-existing condition: A dental condition that exists for a set time prior to enrollment in a dental plan, regardless of whether the condition has been formally diagnosed. The only pre-existing condition that is common for dental plans or policies is a missing tooth. [REMOVED PRECIOUS OR HIGH NOBLE METALS – SEE METALS, CLASSIFICATIONS –ACCORDING TO CDT] Pretreatement Estimate: See predetermination. ** Preferred Provider Organization (PPO): See DPPO. Premedication: The use of medications prior to dental procedures. Prepaid dental plan: A method of funding dental care costs in advance of services. For a defined population. Premium: The amount you pay to a dental insurance company for dental coverage. The dental insurance company generally recalculates the premium each policy year. This amount is usually paid in monthly installments. When you receive dental insurance through an employer, the employer may pay a portion of the premium and you pay the rest, often through payroll deductions. Preventive Services: See diagnostic and preventive services. Primary dentition: Another name for baby teeth. See deciduous. Primary payer: The third party payer with first responsibility in a benefit determination. Prophylaxis: Scaling and polishing procedure. Performed to remove coronal plaque, calculus and stains. ** Prosthodontic: Branch of dentistry that deals with the repair of teeth by crowns, inlays or onlays and/or the replacement of missing teeth and related mouth or jaw structures by bridges, dentures, implants or other artificial devises. Prosthodontist: A dental specialist. Restores natural teeth. Replaces missing teeth with artificial substitutes. Provider: A dentist or other dental care professional, or clinic that is accredited, licensed or certified to provide dental services in their state, and is providing services within the scope of that accreditation, license or certification. Provider network: Dentists and other dental care professionals who agree to provide dental care to members of a dental plan, under the terms of a contract. Use the info in this document and not any other source. Categorize the terms into "Device", "Procedure", and "Other", and exclude any financial or insurance related terms.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Considering Zimbabwe's effort to reduce the financial crisis through focusing on re engaging policies in 2014. How much more was raised in 2017 compared to the money that was raised through bond trading within the first 2 years .Also explain how these bonds have affected the government debt management . Keep the response at 300 words or Less

In 2014, the government for the first time started to trade infrastructure bonds (GoZ, 2014b). The introduction of the 5-year tenor infrastructure bonds at a fixed interest of 9.5 percent, has not only enhanced financial deepening in the economy but also contributed to a paradigm shift in the structure of government debt. Also, the introduction of long term debt instruments by the government was intended at minimising rollover risk and lessen borrowing expenses associated with short term debt (Infrastructure Development Bank of Zimbabwe “IDBZ”, 2016). Until now, the government has raised US$5 million, $15 million and $22 million in 2015, 2016 and 2017, respectively, through the trading of infrastructure bonds on the capital markets (IDBZ, 2015, 2016; GoZ, 2017). At present, the government debt securities are being traded on the Zimbabwe Stock Exchange in the same manner as other stocks. To provide for the management of public debt in Zimbabwe on a statutory basis, mainly foreign public debt, the public debt reforms included public sector financial reforms and the institutionalisation and operationalisation of a Debt Management Office, which is currently housed in the Ministry of Finance and Economic Development. The responsibilities of the Debt Office are among others, to ensure public debt database validation and reconciliation with all creditors and to provide for the raising, management and servicing of loans by the state (GoZ, 2015b). The Public Management Act Amended (2015) further stipulates that the Debt Office shall (1) formulate and publish a Medium Term Debt Management Strategy, (2) formulate and publish an annual borrowing plan, which includes a borrowing limit, and (3) undertake an annual debt sustainability analyses (MOFED, 2012). In 2011, the GNU instituted several foreign policy shifts, intended at reducing the country’s foreign public debt overhang, by re-engaging with creditors and the global community. The intention of the new re engagement policy reform was to seek comprehensive debt relief initiatives, as well as opening up new lines of offshore financing. Accordingly, in 2011, the government started to make paltry debt payments to the Bretton Woods institutions and the African Development Bank, an initiative that was aimed at seeking debt rescheduling (RBZ, 2014). To spearhead the re-engagement process, the government formulated the Accelerated Re-engagement Economic Programme (ZAREP). More so, the formulation of ZAREP was meant to promote fiscal sustainability through proper expenditure management, monitoring and wage policy reviews (GoZ, 2015c: 14). The emergence of Staff Monitored Programme (SMP) between the Zimbabwean government and the International Monetary Fund in 2013 is an indication of the success of the re-engagement policy with its traditional creditors (IMF, 2015). The Staff Monitored Programme focuses on putting public finances on a sustainable course, enhancing public financial management, facilitating diamond revenue transparency, and restructuring the central bank (IMF, 2013). In related institutional and revenue structural reforms, the government in 2015 managed to amalgamate all diamond companies into one, under the name Zimbabwe Consolidated Diamond Corporation (ZCDC) (Parliament of Zimbabwe, 2017: 12). The Zimbabwe Consolidated Diamond Corporation came as result of the IMF’s recommendations to improve on diamond revenue transparency and accountability (

"================ <TEXT PASSAGE> ======= In 2014, the government for the first time started to trade infrastructure bonds (GoZ, 2014b). The introduction of the 5-year tenor infrastructure bonds at a fixed interest of 9.5 percent, has not only enhanced financial deepening in the economy but also contributed to a paradigm shift in the structure of government debt. Also, the introduction of long term debt instruments by the government was intended at minimising rollover risk and lessen borrowing expenses associated with short term debt (Infrastructure Development Bank of Zimbabwe “IDBZ”, 2016). Until now, the government has raised US$5 million, $15 million and $22 million in 2015, 2016 and 2017, respectively, through the trading of infrastructure bonds on the capital markets (IDBZ, 2015, 2016; GoZ, 2017). At present, the government debt securities are being traded on the Zimbabwe Stock Exchange in the same manner as other stocks. To provide for the management of public debt in Zimbabwe on a statutory basis, mainly foreign public debt, the public debt reforms included public sector financial reforms and the institutionalisation and operationalisation of a Debt Management Office, which is currently housed in the Ministry of Finance and Economic Development. The responsibilities of the Debt Office are among others, to ensure public debt database validation and reconciliation with all creditors and to provide for the raising, management and servicing of loans by the state (GoZ, 2015b). The Public Management Act Amended (2015) further stipulates that the Debt Office shall (1) formulate and publish a Medium Term Debt Management Strategy, (2) formulate and publish an annual borrowing plan, which includes a borrowing limit, and (3) undertake an annual debt sustainability analyses (MOFED, 2012). In 2011, the GNU instituted several foreign policy shifts, intended at reducing the country’s foreign public debt overhang, by re-engaging with creditors and the global community. The intention of the new re engagement policy reform was to seek comprehensive debt relief initiatives, as well as opening up new lines of offshore financing. Accordingly, in 2011, the government started to make paltry debt payments to the Bretton Woods institutions and the African Development Bank, an initiative that was aimed at seeking debt rescheduling (RBZ, 2014). To spearhead the re-engagement process, the government formulated the Accelerated Re-engagement Economic Programme (ZAREP). More so, the formulation of ZAREP was meant to promote fiscal sustainability through proper expenditure management, monitoring and wage policy reviews (GoZ, 2015c: 14). The emergence of Staff Monitored Programme (SMP) between the Zimbabwean government and the International Monetary Fund in 2013 is an indication of the success of the re-engagement policy with its traditional creditors (IMF, 2015). The Staff Monitored Programme focuses on putting public finances on a sustainable course, enhancing public financial management, facilitating diamond revenue transparency, and restructuring the central bank (IMF, 2013). In related institutional and revenue structural reforms, the government in 2015 managed to amalgamate all diamond companies into one, under the name Zimbabwe Consolidated Diamond Corporation (ZCDC) (Parliament of Zimbabwe, 2017: 12). The Zimbabwe Consolidated Diamond Corporation came as result of the IMF’s recommendations to improve on diamond revenue transparency and accountability ( http://www.ijqr.net/journal/v12-n1/6.pdf ================ <QUESTION> ======= Considering Zimbabwe's effort to reduce the financial crisis through focusing on re engaging policies in 2014. How much more was raised in 2017 compared to the money that was raised through bond trading within the first 2 years .Also explain how these bonds have affected the government debt management . Keep the response at 300 words or Less ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Model must only respond using information contained in the context block. Model must not rely on its own knowledge or outside sources of information when responding.

What measures did the federal reserve implement in March 2020 to stabilize the commercial paper market during the COVID pandemic?

CRS INSIGHT Prepared for Members and Committees of Congress INSIGHTi COVID-19: Commercial Paper Market Strains and Federal Government Support April 13, 2020 What Is Commercial Paper and Why Is It Important? As COVID-19 spread rapidly in the United States, fears of its economic effects led to strains in the commercial paper (CP) market, one of the main funding sources for many firms and for providers of credit to individuals. Commercial paper is short-term debt issued primarily by corporations and generally is unsecured. The CP market is an important source of short-term credit for a range of financial and nonfinancial businesses, who may rely on it as an alternative to bank loans—for example, in making payroll or for other short-term funding needs. The CP market also helps provide credit to individuals through short-term asset-backed commercial paper (ABCP), which finances certain consumer loans such as auto loans or other consumer debt. Municipalities also issue CP for short-term funding needs. Some money market funds (MMFs) are key purchasers of CP, which plays a significant role in this short-term funding market. As of March 31, 2020, about 24% of total CP outstanding was ABCP; 47% of total CP was from financial issuers; and 28% was from nonfinancial issuers. The total CP market in the United States was $1.092 trillion as of the end of March 2020, though this amount can fluctuate based on market conditions. For a sense of scale, this is roughly 65% of the amount of currency in circulation by the public ($1.73 trillion as of March 9, 2020). The CP market grew rapidly in the 1970s and 1980s in the United States, as a lower-cost alternative to bank loans. A provision in the securities laws allowing for an exemption from more elaborate Securities and Exchange Commission (SEC) registration requirements for debt securities with maturities of 270 days or less helped fuel this market’s rapid expansion. From 1970 to 1991, outstanding commercial paper grew at an annual rate of 14%. The subsequent growth of securitization, in which loans are packaged into bonds and sold to investors as securities, also fueled a rapid expansion of ABCP. Between 1997 and 2007, ABCP grew from $250 billion to more than $1 trillion. This growth was partly fueled by the expansion of residential mortgage securitization. In August 2007, ABCP comprised over 52% of the total CP; financial CP accounted for 38%; and nonfinancial CP constituted 10%. The amount of CP outstanding peaked at $2.2 trillion in August 2007, before shrinking considerably during and after the 2008 financial crisis. Congressional Research Service https://crsreports.congress.gov IN11332 Congressional Research Service 2 Because CP involves short maturities (much CP matures in 30 days or less), many firms have to “roll over” maturing CP—issuing new CP as existing CP matures. Thus, the CP market is generally susceptible to roll-over risk, meaning the risk that market conditions may change and the usual buyers of CP might decline to purchase new notes when existing ones expire, preferring perhaps to hold cash. This is often sparked by credit risk, wherein fears over a CP issuer’s credit, or even the bankruptcy of a CP issuer, lead to depressed demand for commercial paper. The risk of being unable to roll over maturing commercial paper due to credit risk has been demonstrated as real in recent financial history, both in the financial crisis following Lehman Brothers’ collapse and in prior sudden corporate bankruptcies. When credit and liquidity become unavailable through the CP market, the effects can spill over into credit markets more generally. Commercial Paper Market Stress and Federal Government Support As concerns over the spread of COVID-19 grew, stresses in the CP market became linked to the supply of business credit, putting pressure on banks and heightening the market demand for cash. Such strains on credit markets can sharply increase borrowing costs for financial and nonfinancial firms. When investment bank Lehman Brothers failed during the 2008 crisis, the cost of borrowing in CP, as measured by the spread for CP borrowing rates over more stable overnight index swap rates, rose by about 200 basis points (2%) in the following week, and the rates for financial firms’ CP notes eventually climbed higher. Data from the Federal Reserve shown in Figure 1 indicate that CP borrowing rates for financial issuers, as measured in spreads for CP borrowing rates over Treasuries, spiked by about 200 basis points in March 2020, as investors grew reluctant to buy new CP. To add liquidity and foster credit provision in the CP market, the Federal Reserve intervened on March 17, 2020, with a credit facility. Figure 1. Spreads Between 1-Month and 3-Month AA-rated Financial Commercial Paper and 3-Month Constant Maturity Treasury Rates Source: CRS, based on data obtained from the Federal Reserve Bank of St. Louis FRED website. Congressional Research Service 3 IN11332 · VERSION 1 · NEW Note: “AA-rated” is the second-highest credit rating. For more information, see the Federal Reserve Bank of New York website. On March 17, the Federal Reserve (Fed) announced that it was establishing a Commercial Paper Funding Facility (CPFF) to support the flow of credit to households and businesses. This facility is backed by funding from the Treasury’s Economic Stabilization Fund. The Fed noted the CPFF was designed to support the CP markets, which “directly finance a wide range of economic activity, supplying credit and funding for auto loans and mortgages as well as liquidity to meet the operational needs of a range of companies.” The Fed aims to provide a liquidity backstop to CP issuers by buying both ABCP and regular, unsecured CP of a minimum credit quality from eligible companies. By acting as a buyer of the last resort, the Fed program aims to reduce investors’ risk that CP issuers would not repay them because they became unable to roll over any maturing CP. On March 23, the Fed expanded the CPFF to facilitate the flow of credit to municipalities by including high-quality, tax-exempt commercial paper as eligible securities, and also reduced the pricing of the facility. (For more information, see CRS Insight IN11259, Federal Reserve: Recent Actions in Response to COVID-19, by Marc Labonte; and CRS Report R44185, Federal Reserve: Emergency Lending, by Marc Labonte.) Author Information Rena S. Miller Specialist in Financial Economics Disclaimer This document was prepared by the Congressional Research Service (CRS). CRS serves as nonpartisan shared staff to congressional committees and Members of Congress. It operates solely at the behest of and under the direction of Congress. Information in a CRS Report should not be relied upon for purposes other than public understanding of information that has been provided by CRS to Members of Congress in connection with CRS’s institutional role. CRS Reports, as a work of the United States Government, are not subject to copyright protection in the United States. Any CRS Report may be reproduced and distributed in its entirety without permission from CRS. However, as a CRS Report may include copyrighted images or material from a third party, you may need to obtain the permission of the copyright holder if you wish to copy or otherwise use copyrighted material.

CRS INSIGHT Prepared for Members and Committees of Congress INSIGHTi COVID-19: Commercial Paper Market Strains and Federal Government Support April 13, 2020 What Is Commercial Paper and Why Is It Important? As COVID-19 spread rapidly in the United States, fears of its economic effects led to strains in the commercial paper (CP) market, one of the main funding sources for many firms and for providers of credit to individuals. Commercial paper is short-term debt issued primarily by corporations and generally is unsecured. The CP market is an important source of short-term credit for a range of financial and nonfinancial businesses, who may rely on it as an alternative to bank loans—for example, in making payroll or for other short-term funding needs. The CP market also helps provide credit to individuals through short-term asset-backed commercial paper (ABCP), which finances certain consumer loans such as auto loans or other consumer debt. Municipalities also issue CP for short-term funding needs. Some money market funds (MMFs) are key purchasers of CP, which plays a significant role in this short-term funding market. As of March 31, 2020, about 24% of total CP outstanding was ABCP; 47% of total CP was from financial issuers; and 28% was from nonfinancial issuers. The total CP market in the United States was $1.092 trillion as of the end of March 2020, though this amount can fluctuate based on market conditions. For a sense of scale, this is roughly 65% of the amount of currency in circulation by the public ($1.73 trillion as of March 9, 2020). The CP market grew rapidly in the 1970s and 1980s in the United States, as a lower-cost alternative to bank loans. A provision in the securities laws allowing for an exemption from more elaborate Securities and Exchange Commission (SEC) registration requirements for debt securities with maturities of 270 days or less helped fuel this market’s rapid expansion. From 1970 to 1991, outstanding commercial paper grew at an annual rate of 14%. The subsequent growth of securitization, in which loans are packaged into bonds and sold to investors as securities, also fueled a rapid expansion of ABCP. Between 1997 and 2007, ABCP grew from $250 billion to more than $1 trillion. This growth was partly fueled by the expansion of residential mortgage securitization. In August 2007, ABCP comprised over 52% of the total CP; financial CP accounted for 38%; and nonfinancial CP constituted 10%. The amount of CP outstanding peaked at $2.2 trillion in August 2007, before shrinking considerably during and after the 2008 financial crisis. Congressional Research Service https://crsreports.congress.gov IN11332 Congressional Research Service 2 Because CP involves short maturities (much CP matures in 30 days or less), many firms have to “roll over” maturing CP—issuing new CP as existing CP matures. Thus, the CP market is generally susceptible to roll-over risk, meaning the risk that market conditions may change and the usual buyers of CP might decline to purchase new notes when existing ones expire, preferring perhaps to hold cash. This is often sparked by credit risk, wherein fears over a CP issuer’s credit, or even the bankruptcy of a CP issuer, lead to depressed demand for commercial paper. The risk of being unable to roll over maturing commercial paper due to credit risk has been demonstrated as real in recent financial history, both in the financial crisis following Lehman Brothers’ collapse and in prior sudden corporate bankruptcies. When credit and liquidity become unavailable through the CP market, the effects can spill over into credit markets more generally. Commercial Paper Market Stress and Federal Government Support As concerns over the spread of COVID-19 grew, stresses in the CP market became linked to the supply of business credit, putting pressure on banks and heightening the market demand for cash. Such strains on credit markets can sharply increase borrowing costs for financial and nonfinancial firms. When investment bank Lehman Brothers failed during the 2008 crisis, the cost of borrowing in CP, as measured by the spread for CP borrowing rates over more stable overnight index swap rates, rose by about 200 basis points (2%) in the following week, and the rates for financial firms’ CP notes eventually climbed higher. Data from the Federal Reserve shown in Figure 1 indicate that CP borrowing rates for financial issuers, as measured in spreads for CP borrowing rates over Treasuries, spiked by about 200 basis points in March 2020, as investors grew reluctant to buy new CP. To add liquidity and foster credit provision in the CP market, the Federal Reserve intervened on March 17, 2020, with a credit facility. Figure 1. Spreads Between 1-Month and 3-Month AA-rated Financial Commercial Paper and 3-Month Constant Maturity Treasury Rates Source: CRS, based on data obtained from the Federal Reserve Bank of St. Louis FRED website. Congressional Research Service 3 IN11332 · VERSION 1 · NEW Note: “AA-rated” is the second-highest credit rating. For more information, see the Federal Reserve Bank of New York website. On March 17, the Federal Reserve (Fed) announced that it was establishing a Commercial Paper Funding Facility (CPFF) to support the flow of credit to households and businesses. This facility is backed by funding from the Treasury’s Economic Stabilization Fund. The Fed noted the CPFF was designed to support the CP markets, which “directly finance a wide range of economic activity, supplying credit and funding for auto loans and mortgages as well as liquidity to meet the operational needs of a range of companies.” The Fed aims to provide a liquidity backstop to CP issuers by buying both ABCP and regular, unsecured CP of a minimum credit quality from eligible companies. By acting as a buyer of the last resort, the Fed program aims to reduce investors’ risk that CP issuers would not repay them because they became unable to roll over any maturing CP. On March 23, the Fed expanded the CPFF to facilitate the flow of credit to municipalities by including high-quality, tax-exempt commercial paper as eligible securities, and also reduced the pricing of the facility. (For more information, see CRS Insight IN11259, Federal Reserve: Recent Actions in Response to COVID-19, by Marc Labonte; and CRS Report R44185, Federal Reserve: Emergency Lending, by Marc Labonte.) Author Information Rena S. Miller Specialist in Financial Economics Disclaimer This document was prepared by the Congressional Research Service (CRS). CRS serves as nonpartisan shared staff to congressional committees and Members of Congress. It operates solely at the behest of and under the direction of Congress. Information in a CRS Report should not be relied upon for purposes other than public understanding of information that has been provided by CRS to Members of Congress in connection with CRS’s institutional role. CRS Reports, as a work of the United States Government, are not subject to copyright protection in the United States. Any CRS Report may be reproduced and distributed in its entirety without permission from CRS. However, as a CRS Report may include copyrighted images or material from a third party, you may need to obtain the permission of the copyright holder if you wish to copy or otherwise use copyrighted material. Model must only respond using information contained in the context block. Model must not rely on its own knowledge or outside sources of information when responding. What measures did the federal reserve implement in March 2020 to stabilize the commercial paper market during the COVID pandemic?

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What are the essential steps and key points from the customer discovery process outlined in "Talking to Humans"?

TALKING TO HUMANS Success starts with understanding your customers GIFF CONSTABLE with Frank Rimalovski illustrations by Tom Fishburne and foreword by Steve Blank Copyright ©2014 Gif Constable First edition, v1.71 All rights reserved. Book design: Gif Constable Illustrations by Tom Fishburne Cover design assistance: Jono Mallanyk Lean Startup is trademarked by Eric Ries Customer Discovery is a phrase coined by Steve Blank ISBN: 978-0-9908009-0-3 Special thanks to the NYU Entrepreneurial Institute for their collaboration and support in the creation of Talking to Humans Acclaim for Talking to Humans “If you are teaching entrepreneurship or running a startup accelerator, you need to make it required reading for your students and teams. I have.” Steve Blank, entrepreneur, educator and author of Four Steps to the Epiphany and The Startup Owner’s Manual “If entrepreneurship 101 is talking to customers, this is the syllabus. Talking to Humans is a thoughtful guide to the customer informed product development that lies at the foundation of successful start-ups.” Phin Barnes, Partner, First Round Capital “Getting started on your Customer Discovery journey is the most important step to becoming a successful entrepreneur and reading Talking To Humans is the smartest frst step to fnding and solving real problems for paying customers.” Andre Marquis, Executive Director, Lester Center for Entrepreneurship University of California Berkeley “A lot of entrepreneurs pay lip service to talking to customers but you have to know how. Talking to Humans ofers concrete examples on how to how to recruit candidates, how to conduct interviews, and how to prioritize learning from customers more through listening versus talking.” Ash Maurya, Founder Spark59 and Author of Running Lean “Tis is a great how-to guide for entrepreneurs that provides practical guidance and examples on one of the most important and ofen under practiced requirements of building a great startup—getting out of the ofce, talking directly with customers and partners, and beginning the critical process of building a community.” David Aronoff, General Partner, Flybridge Capital “Gif has been one of the thought leaders in the lean startup movement from the very beginning. Entrepreneurs in all industries will fnd Talking to Humans practical, insightful, and incredibly useful.” Patrick Vlaskovits, New York Times bestselling author of The Lean Entpreneur “Current and future customers are the best source of feedback and insight for your new product ideas. Talking to them is intimidating and seemingly time-consuming. In this focused, practical, down-to-earth book Gif Constable demystifes the art (not science) of customer discovery helping entrepreneurs and product veterans alike learn how to build a continuous conversation with their market and ensure the best chances of success for their ideas. Want to know what your audience is thinking? Read this book!” Jeff Gothelf, author of LeanUX “When getting ‘out of the building,’ too many people crash and burn right out of the gate and wonder what happened. Talking to Humans is a quick and efective guide for how Lean Startup interviews should be done: who to talk to, how to talk your way in the door, and how to gain the most insight and learning. Don’t crash and burn – read Talking to Humans!” Dean Chang, Associate Vice President for Innovation & Entrepreneurship University of Maryland “A must read for anyone who is considering creating a startup, developing a new product or starting a new division. Read this book frst – a great guide to the evolving art of customer discovery. Don’t waste your time building products that your customer may or may not want. Before you write the frst line of code, pitch your idea to investors or build the frst prototype, do your self a favor, read this book and follow the advice! I guarantee you will make better decisions, build a better product and have a more successful company.” John Burke, Partner, True Ventures “Primary market research has been around for a long time because it has stood the test of time and proved that it is fundamental to building a successful venture; it underlies all that we do at MIT in entrepreneurship. Te question is how we more broadly deployed appropriate skills to entrepreneurs so they can be guided to do this in an efcient and efective manner while maintaining rigor. With all the sloganeering out there on the topic, this book stands out in that it delivers real value to the practitioner in this regard.” Bill Aulet, Managing Director, Martin Trust Center for MIT Entrepreneurship “Talking to strangers can be scary, but it’s vital to launching any new product. Trough storytelling, Gif Constable makes customer development concepts accessible. Tis book will show you how to articulate assumptions, get useful information and turn it into meaningful insights. Ten it delivers practical advice you can use immediately to test your ideas. Fear holds people back. Tis book will give you the confdence to jump.” Andres Glusman, Chief Strategy Offcer, Meetup.com Table of Contents 8 Foreword 11 Introduction 14 The Story 28 Lessons Learned 30 How To 31 Getting Started with Customer Discovery 32 Who Do You Want to Learn From? 36 What Do You Want to Learn? 44 How Do You Find Your Interview Subjects? 52 How to Ensure an Effective Session? 58 How Do You Make Sense of What You Learn? 65 Conclusion 66 Appendix 67 Cold Approach Examples 69 Business Assumptions Exercise 72 Teaching Exercise #1: Mock Interviews 74 Teaching Exercise #2: Mock Approach 76 Screwing Up Customer Discovery 80 Glossary 82 Other Learning Resources 83 Behind the Book 8 Talking to Humans Foreword “Get out of the building!” Tat’s been the key lesson in building startups since I frst started teaching customer development and the Lean Launchpad curriculum in 2002. Since then, a lot has happened. Te concepts I frst outlined in my book Te Four Steps to the Epiphany have grown into an international movement: Te Lean Startup. Te class I developed - Te Lean Launchpad - is now taught at Stanford, UC Berkeley, Columbia University, UCSF, and most recently New York University (NYU). More than 200 college and university faculty have taken my Lean Launchpad Educators Seminar, and have gone on to teach the curriculum at hundreds of universities around the globe. Te National Science Foundation, and now the National Institute of Health, use it to commercialize scientifc research as part of their Innovation Corps (I-Corps) program. My How to Build a Startup class on Udacity has been viewed by over 225,000 students worldwide. During the past few years, we’ve seen dozens of large companies including General Electric, Qualcomm and Intuit begin to adopt the lean startup methodology. Te Lean Startup turns the decades-old formula of writing a business plan, pitching it to investors, assembling a team, and launching and selling a product on its head. While terms like “pivot” and “minimum viable product” have become widely used, they are not understood by many. Te same can be said of “getting out of the building”. Many entrepreneurs “get out” and get in front of customers, but take a simplistic view and ask their customers what they want, or if they would buy their startup’s (half-baked) product. Te “getting out” part is easy. It is the application of the customer Foreword & Introduction 9 development methodology and the testing of their hypotheses with users, customers and partners that is both critical and ofen difcult for entrepreneurs to grasp in the search for a scalable and repeatable business model. Since the Four Steps, many other books have been written on customer development including Te Startup Owner’s Manual, Business Model Generation, Te Lean Startup, and others. Each of these texts has advanced our understanding of the customer development methodology in one way or another, teaching aspiring students and entrepreneurs the what, when and why we should get out of the building, but have only skimmed the surface on “how” to get out of the building. For both my own classes as well as I-Corps, I always made Gif Constable’s blog post “12 Tips for Early Customer Development Interviews” required reading. It answered the “how” question as well. Now Gif has turned those 12 tips into an entire book of great advice. In a comprehensive, yet concise and accessible manner, Talking to Humans teaches you how to get out of the building. It guides students and entrepreneurs through the critical elements: how to fnd interview candidates, structure and conduct efective interviews and synthesize your learning. Gif provides ample anecdotes as well as useful strategies, tactics and best practices to help you hit the ground running in your customer discovery interviews. If you are a student, aspiring entrepreneur or product manager trying to bring the value of getting out of the building to an existing company, Talking to Humans is a must read. It is chock full of lessons learned and actionable advice that will enable you to make the most of your time out of the building. Talking to Humans is the perfect complement to the existing 10 Talking to Humans body of work on customer development. If you are teaching entrepreneurship or running a startup accelerator, you need to make it required reading for your students and teams. I have. Steve Blank September 3, 2014 Foreword & Introduction 11 Introduction 12 Talking to Humans Te art of being a great entrepreneur is fnding the right balance between vision and reality. You are probably opening this book because you want to put something new in the world. Tat’s an incredibly powerful and meaningful endeavor. It’s also scary and extremely risky. How can you get ahead of that risk and beat the odds? Every new business idea is built upon a stack of assumptions. We agree with Steve Blank’s insight that it is better to challenge your risky assumptions right at the start. You can’t challenge anything sitting in a conference room. You have to get into the market, or, as Blank likes to say, “Get out of the building!” Tere are two efective ways to do this: 1. talk directly to your customers and partners, and observe their behavior; 2. run experiments in which you put people through an experience and track what happens. Tis book focuses on the frst. Te qualitative part of customer discovery is surprisingly hard for most people, partly because talking to strangers can feel intimidating, and partially because our instincts on how to do it are ofen wrong. Here’s what customer discovery is not: It is not asking people to design your product for you. It is not about abdicating your vision. It is also not about pitching. A natural tendency is to try to sell other people on your idea, but your job in customer discovery is to learn. You are a detective. You are looking for clues that help confrm or deny your assumptions. Whether you are a tiny startup or an intrapreneurial team within a big company, your goal is not to compile statistically signifcant answers. Instead you want to look for patterns that will help you make better decisions. Tose decisions should lead to action, and smart action is what you need for success. Foreword & Introduction 13 Tis book was written as a focused primer on qualitative research to help you get started. You should view it as a complement to the other excellent resources out there on customer development and lean innovation. It is not a rulebook, but hopefully you will fnd the principles included here useful. Te book comes in two parts. It begins with a fctional story of two entrepreneurs doing customer research for the frst time. Te second part is a mix of theory and tactics to guide you through the core steps of customer discovery. While the fctional story highlights a consumer-facing business, I should note that there are plenty of tips in this book for teams who sell to the enterprise. Some last words to kick things of: entrepreneurs have a tendency to over-obsess about their product to the neglect of other business risks. Tey also tend to stay inside their heads for far too long. I urge you to be brave, get out of the building, and go talk to real human beings. Gif Constable August 2014 Some Thanks Are Due Many thanks to Frank Rimalovski for encouraging me to write this, and his students and team at NYU for providing early feedback, Steve Blank for the foreword and his inspiration and leadership on the topic of entrepreneurship, Tom Fishburne for his great illustrations, Josh Seiden and Jef Gothelf for their insights, my colleagues at Neo for continuing to push forward the craf of customer development, the many speakers and members of New York’s Lean Lessons Learned meetup who have shared their stories with me, and Eric Ries for inspiring me and so many others. The Story PART ONE The Story 15 Breakthrough Koshi and Roberta had so much adrenaline pumping through their systems that neither could sleep that night. Afer a year of challenging lab work, they had fnally cracked it. Tey were now sure they could manufacture artifcial down feathers cost-efectively. Teir insomnia was ironic, since their very dream was to transform the quality of people’s sleep through the invention of a better pillow. Tey knew they had a technical advantage. Teir artifcial down had heightened levels of insulation, a better resilience/resistance quotient, and was kinder to both animals and the environment. Now the question was, did they have a business? The Advisor Tey called a meeting with their entrepreneurial advisor the next day. Samantha had built four companies, successfully exiting two of them. She was now an angel investor and believed frmly in giving back by working with frst-time entrepreneurs. “We fnally cracked it!” Roberta blurted out. “What she means,” Koshi said, “is that we’re convinced we can manufacture NewDown in a cost-efective and repeatable manner. Now we think we can make a real business.” “So you want to know if the time has come to jump in feet frst?” asked Samantha. Te two scientists nodded. “If you want to be successful bringing something to market, you need to understand the market. Do you feel like you know when and why people buy pillows today?” “Not really,” Roberta said. “We’ve spent our time in the lab focused on the product side.” “I suspected so. Founders commonly obsess about product at the 16 Talking to Humans expense of the understanding the customer or the business model. You need to work on it all, and you have to challenge your thinking. Behind your startup is a belief system about how your business will work. Some of your assumptions will be right, but the ones that are wrong could crater your business. I want you to get ahead of the risky hypotheses that might cause failure.” Samantha had the founders list out the riskiest hypotheses. 1. We believe that people care about sleep quality when making a pillow purchase decision. 2. We believe that we can sell online directly to customers. 3. We believe that our customers will be young urban professionals. 4. We believe that our very frst customers will be new graduates who need to outft their apartments. 5. We believe that we can sell our pillows at a high enough price to cover our costs. 6. We believe that we can raise enough capital to cover investments in manufacturing. “Let’s put aside the fundraising risk right now,” Samantha said. “It’s what everyone jumps to, but you need to strengthen your story frst. Many of your risks are tied to your customer. I like attacking a problem from multiple directions and recommend three approaches. First, I want you to walk a day in your customer’s shoes and actually go out and buy a pillow. Second, I want you to observe people in the process of buying a pillow. And third, I want you to talk directly to them.” “Talk to people?” said Koshi. “I’m a scientist, not a salesperson. If I simply asked someone if my pillow was better, they would have no idea. If I asked them if they would buy my pillow, I couldn’t trust The Story 17 the answer. So what is the point?” “Your job right now isn’t to sell, but rather to learn. You are right, though: getting the customer to speculate is rarely useful,” Samantha said. “You need to understand your market. How does your customer buy? When do they buy? Why do they buy? Where do they buy? As a scientist, you are fully capable of doing research, gathering data, and seeing if your data supports your hypotheses. I promise you, if you are polite and creative, people will be more receptive to you than you might think.” “Buying. Observing. Talking. Do we really need to do all three? Can we really aford to spend the time?” “Can you aford not to? Each of the three approaches is imperfect, but together you should see patterns. By walking in your customer’s shoes you will gain empathy and personal understanding, but you don’t want to rely solely on your own experience. By watching people shop, you can witness honest behavior, but you won’t be able to get into their heads to know their motivations. By talking to people, you gather intel on both behavior and motivation, but you have to be careful not to take what you hear too literally. Each method has strengths and weaknesses, but taken together you will learn a ton. You will have a lot more confdence that you are either on the right track, or that you have to make changes to your plans. It is far better to discover bad assumptions now, before you have invested a lot! Now, how do you think you should proceed?” “We want our customers to buy online from us, so I guess we should also buy our own pillow online,” said Roberta. “And we can observe people shopping by going to a home goods store.” “Tat sounds good,” said Samantha. “You will want to talk to some of those people in the store as well. I see one catch: you will be 18 Talking to Humans targeting the moment of purchase but not the type of customer you are hoping for. One of your risk assumptions was specifcally about young urban professionals and new graduates, so what can you also do to target and connect with them?” “What about going to a cofee shop near the downtown ofce buildings as people are going to work?” Koshi said. “Can’t we just hit up some of the people we used to know in college who are now in the working world?” Roberta said. “Why don’t you try both, and see which approach works better,” said Samantha. “Roberta, I would also ask your friends if they will refer you to their friends. It’s best to talk to people who aren’t too close to you. You don’t want a someone’s afection for you to steer what they have to say. “Let’s start by thinking through the questions you want to ask. It always makes sense to prioritize what you want to learn. You should write down an interview plan, even if you don’t completely stick to it. Break the ice, and then get them to tell you a story about buying a pillow!” Te scientists sketched out a plan: Intro: hello, I’m a PhD candidate at Hillside University and I’m researching sleep quality. I’m asking people about the last time they bought a pillow. Would you mind if I asked a few questions? When was the last time you bought a pillow? Why did you go looking for a pillow? How did you start shopping for a pillow? Why did you choose the one you bought? After you bought, how did you feel about the pillow you purchased? The Story 19 Are you going to be in the market for a pillow anytime soon? “Tat’s a great start,” Samantha said. “Keep good notes as you go, and remember to regularly regroup to review your fndings and look for patterns. Be mindful of which method you used as you discuss your observations.” Walking in the Customer’s Shoes Koshi and Roberta got together the next day afer both purchasing a pillow online. “I found it all a bit frustrating,” said Roberta. “It was hard to learn why you would choose down feathers, cotton, or foam. Te manufacturer websites felt like they were from the 1990s. Tere were some reviews available on Amazon and Bed Bath & Beyond, which helped. In my interpretation, about 65% of reviews talked about sleep quality, which seems like a good sign for our frst risk. A lot of the reviews had to do with personal preference for frm versus sof pillows. I think we can ofer both kinds eventually, but we likely need to choose one at the beginning and that could impact some of our assumptions around market size. ” “I started out by searching Google,” said Koshi. “Amazon and BB&B dominated the results, as we expected, but there were a few specialty providers like BestPillow that ranked high. BestPillow lets you navigate their website by sleep issue, such as snoring or neck pain, which I found interesting. While I see some makers pushing hypoallergenic oferings, I didn’t see anyone who could meet our claims of being environmentally friendly. I agree that all the manufacturer websites felt ancient. I think there’s an opportunity to be smart about search engine optimization and really stand out if we can get the messaging right. I guess our next step is to visit the retail 20 Talking to Humans stores.” Observing the Customer Roberta ended up going to a Bed Bath & Beyond while Koshi went to a local department store. She watched three diferent people come in and pick through several diferent pillows, puzzling over the packaging material. One of them asked a store employee for help, and two pulled out their mobile phones to look online. She then watched a woman go right to a particular shelf, grab a pillow and head back to the aisle. Roberta’s plan was to balance observation and interaction, so she decided to jump in. “Pardon me,” she said “I am trying to fgure out which pillow to purchase and noticed that you went right to that one. Might I ask why you chose that pillow?” “Oh, I replaced some ratty old pillows in my house a few weeks ago,” the woman said, “and I liked this one so much that I thought I would replace my whole set.” “Do you mind if I ask how you decided to buy that pillow in the frst place? My name is Roberta, by the way.” “Nice to meet you, Roberta. I’m Susan. Well, I guess I started by researching online and...” A day later, the founders met to compare notes. “Te BB&B had good foot trafc,” Roberta said, “and I was able to watch ffeen people, and speak to ten. Of the ten, one knew what she wanted going into the store, three were basing their purchase just on packaging and store price, and six did Google searches on their phones, right there in the store. Tey were looking up reviews and pricing. You mentioned search engine optimization earlier — I think it could be even stronger with a fabulous mobile experience.” She looked down at her notes. “I also found that seven out of ten were trying to choose a pillow specifcally for better sleep, although their sleep problems were diverse. Finally, when I asked The Story 21 them why they were buying a pillow, the folks over 40 seemed to be in replacement mode, while the folks under 40 seemed to be reacting to a life change. Two people were moving to a bigger house from an apartment. Another person was moving in with their girlfriend, and another said that she got a new job and could now aford nicer things.” “I went to the home goods section of a high-end department store,” said Koshi. “I saw eighteen people, and fve of them knew what they wanted already. Te rest spent time puzzling over the packaging and, like your group, going online with their mobile phone. I spoke to nine shoppers. I said that I was a scientist trying to invent a new pillow. People thought that was pretty cool. Two of them admitted that they were buying the highest price pillow because they assumed that it had to be the best. Two got the cheapest because it was the cheapest. Te others had specifc preferences for down, cotton or foam based on the frmness they were looking for in a pillow. Te frmness preference seemed to be tied to a belief that they would sleep more soundly. On price, I was relieved to see that the prices of the better pillows were in line with what we were hoping to charge.” Roberta pulled out a pad. “So we saw thirty-three people and spoke to nineteen. Our sample set is still small, but Samantha told us to look for patterns and not worry about statistical signifcance right now. If we break our observations into a few metrics, what have we learned?” • 24% of shoppers knew what they wanted when they walked in • 52% looked up information on their phone in the store • 45% of shoppers purchased a mid-priced or high-priced pillow • 68% of the people we spoke to indicated that better sleep was a major driver of their choice 22 Talking to Humans • 37% of the people we spoke to were reacting to a life change • 37% of the people we spoke to were in replacement mode “I think the use of mobile phones is something we need to pay attention to and work into our strategy,” Koshi said. “I guess for our next step, we should follow Samantha’s suggestions to target urban professionals.” Regrouping A week and many interviews later, the team sat down with Samantha. “How did things go?” she asked. “I went to a downtown cofee shop at peak hour,” Koshi said. “At frst, everyone was in such a hurry to get to work that I didn’t get much response, but then I made a little sign I held up outside that promised ‘cofee for science,’ which started to get laughs and a lot of curiosity. I ended up talking to about ffeen people who matched our target of young urban professionals. I got to talk to them for about fve to twenty minutes each. It was actually very enjoyable. “One clear pattern was that people right out of school tended to have no clue. Tey either had never bought a pillow themselves, or if they had, it had been the cheapest thing they could get. A few admitted that they were probably going to buy new bedding. I know it is speculation, but I asked them to guess how they might go about looking for a pillow, based on how they shop for other things. Te common responses were searching on Google or Amazon, or walking into a Bed Bath & Beyond. “Te few folks in their later twenties or thirties whom I spoke to had usually bought at least one pillow — some from Amazon and some from retailers. Te ones who liked a frm pillow avoided The Story 23 down feathers. Te ones who wanted to upgrade to fancier duvets and high thread-count sheets all seemed to go with duck and goose feathers. Tey didn’t know any brands and instead relied on product packaging. Amazon buyers did actually read the reviews. All these folks were only planning on buying new pillows when they were moving to a bigger apartment because they were getting married or something.” “Yes, that aligns with what we learned when we spoke to people in the retail stores and what I saw with my other interviews,” said Roberta. “Pillow buying seems to be tied to life events like moving and marriage and such. I interviewed a diferent group. A whole bunch of our old classmates responded to my email or my Facebook post. I even had some folks pass me on to their friends, and so I got to talk to some people who didn’t go to school with us. “Like you, I saw a lag efect afer someone graduated from college. When new graduates told me that they had not spent any money on their linens yet, I inquired further and found out that their initial spending money was predominately going towards clothes. I spoke to twelve people between 22 and 25, and roughly 60% had actually bought a pillow in the last few years. I saw similar trends as you, although most went right to Google, Amazon or a few specialty online retailers. It seemed like a very online crowd. Te price sensitive ones stayed away from down. Tey didn’t have much to go on for brand, but the reviews helped. Te women defnitely cared more about quality and put more efort into their hunt.” “Te good news is that everyone thought inventing a new pillow was an awesome idea!” said Koshi. Samantha chuckled. “Of everything I’ve heard you say, that last bit is probably the least useful. It’s easy to say something is cool. It’s another thing to actually buy. Te good news is, you are a lot more educated about your market than you were last time we met. 24 Talking to Humans I see from your notes that you have either spoken to or observed 72 people. We should be able to see some patterns from that. Let’s revisit our critical assumptions.” Challenging Assumptions Te team looked at their initial list. 1. We believe that people care about sleep quality when making a purchase decision. “68% of the retail shoppers indicated that this was a major factor,” said Roberta. “Of our young urban professionals, we were able to ask this of only a portion of our interviewees. Only 56% indicated that it was a factor, but if we factor out the new graduates, it was more like 70%. We’ve also read a lot of online reviews and have seen this come up repeatedly. We feel reasonably confdent that this is a common decision point in choosing a pillow,” said Koshi. “I’m glad you are approaching this with rigor and actually calculating metrics from your observations,” said Samantha. “Tat will prevent you from letting innate biases override your actual results. However, one word of advice. At this stage, don’t take any of your statistics too literally and don’t let any single number dominate your strategic thinking. Just as we’re not looking for statistical signifcance at this point, we also don’t want to start treating our results as if they are indisputable facts. How about the next assumption?” 2. We believe that we can sell online directly to customers. “We have seen some promising signs. 77% of our urban professionals start researching purchases with a search engine. Te question is whether they would discover, visit, or convert with our The Story 25 online store. We did see a ton of mobile usage in the retail stores and think there might be a chance to steal those customers if we have good enough search engine optimization. Overall, our conclusion is that we need more data here.” 3. We believe that our customers will be young urban professionals. “I need to run some numbers on size of market and the number of purchases we might expect from this group, but we still feel like this is a good group for us. We clearly saw purchase behavior. Tey want, and can aford, quality things, and prefer to buy things online.” 4. We believe that our very frst customers will be new graduates who need to outft their apartments. “Tis is where we were totally wrong. Buying behavior, or at least the willingness to buy something that isn’t the cheapest option, did not seem to be very prevalent among new grads. Only 25% of the newly minted grads we spoke with had purchased a pillow on their own. Instead, the evidence points us towards people in their mid-tolate twenties or early thirties. “We also saw a correlation between purchasing and life changes. While this was only 37% with our retail shoppers, it was 70% of our urban professionals. From an early adopter perspective, I wonder if we can do well targeting people who are getting married or moving to a larger apartment or house?” 5. We believe we can sell our pillows at a high enough price to cover our costs. “45% of our retail shoppers bought at least a mid-priced pillow. We admit that we visited reasonably high-end stores, but that was still a nice statistic to see. Te good news is that our initial target price is comparable with the high-end of the current market. We 26 Talking to Humans won’t be proftable at the beginning, but if we can scale and improve our manufacturing process then we can move into the black. Of course, they have to want to buy our pillow.” Samantha nodded. “To test that, you will need to actually try selling a few, which ties back to your second risk. But I’m glad you have spent time learning rather than rushing to sell. Overall, it sounds like you have gotten some solid intel. I’m also glad you caught the issue with college grads before you spent a lot of money and energy trying to target them. Have your eforts uncovered new risks or worries?” “I’m both excited and worried by how confused customers are,” Koshi said. “Every brand promises a better night’s sleep. I’m also worried about signals we picked up that the market might be divided into those who want a frm pillow versus a sof pillow. We think that’s erroneous thinking. Our pillow lands in the middle, and our studies show better results. I don’t know if people will believe our data. We really need to get the messaging right.” “As for me,” Roberta said, “I’m most worried about the size of our initial market, how quickly we could grow, and if we can survive to proftability.” “I’m not surprised,” said Samantha. “I have some suggestions. One of you should continue doing these interviews, but try adding a new spin. You are both worried about diferentiation and if people will understand or appreciate the proof from your scientifc studies. Let’s test some messaging. Given what you have said about mobile usage, maybe create an infographic that tries to make your case. Show it to people on a phone. Ask them to explain it to you. First you can see if they understand it, and then if they fnd it meaningful. “Expanding from qualitative research, I also think one of you should create a fnancial model that lets you play with how much The Story 27 you charge, how many items you might sell, and what your costs will be. Take into account what you have learned so far and see if your business model adds up. “Finally, I think you’ve learned enough to run some experiments around customer acquisition and sales. It is straightforward to create a basic online store using one of the hosted services. You can test selling a few pillows before you invest in manufacturing capability. Try driving trafc through Google or Facebook ads, and run some A/B tests around ad copy, landing-page messaging and price points. Study your metrics. Ten follow up with your customers and interview them on their buying process and decision.” Roberta’s eyes widened. “Wow. Maybe we can get our frst paying customer!” “Exactly,” said Samantha. “Just remember Steve Blank’s phrase about startups: you are in search of a scalable and repeatable business model. Run these experiments and keep in mind that your mission at this point is to learn before you scale. Don’t stop talking directly to customers. Your questions will likely evolve, but no matter what stage you are in, you’ll usually fnd that your best insights will come from talking to real people and observing real behavior.” 28 Talking to Humans Lessons Learned The Story 29 So what are the key takeaways from Roberta and Koshi’s adventure? 1. Customer discovery is about gaining much deeper insight into your customer, or your partners, or your market 2. Being told your idea is cool is not useful; seeing behavior that validates your customer’s willingness to buy is very useful 3. Prepare an interview guide before you get out of the building 4. To ask the right questions, you need to understand your risks and assumptions 5. Get creative when trying to recruit people — if at frst you don’t succeed, try something new 6. Sometimes observation is as powerful as interviews 7. Take good notes, especially on your key risks, so that you can calculate metrics later. Even better, set your target goals ahead of time! 8. Bring learning back and analyze your patterns as a team 9. Never stop asking hard questions about your business In the next section of this book, we’re going to dive into tactics and talk about all this and more in detail. How To PART TWO How To 31 Getting Started with Customer Discovery Qualitative research, i.e. talking to humans, is something you never want to stop doing, but it can defnitely feel intimidating at frst. Te good news is that if you go about it in a professional and thoughtful way, you will fnd lots of people who are willing to help and give you some of their valuable time. You need to begin with a core set of questions: t
Who do you want to learn from? t
What do you want to learn? t
How will you get to them? t
How can you ensure an efective session? t
How do you make sense of what you learn? 32 Talking to Humans Who Do You Want to Learn From? How To 33 If your desired customer is a doctor, it stands to reason that it won’t help you much talking to a plumber. If you were aiming for teenagers, would you talk to grandparents? Te frst step in trying to learn from the market is having an opinion about who your market actually is. I recommend thinking about a few categories: t
Te typical customer you envision if you get traction with your idea t
Your early adopter, i.e. the people who will take a chance on your product before anyone else t
Critical partners for distribution, fulfllment, or other parts of your business You might think you are creating a product for “everyone”, but that is not an actionable or useful description in the early stages. You need to get more specifc. Your job is to think through the kinds of people who have the problem you are interested in solving. Sometimes they have a particular job, or a state of mind, live in a particular part of the world, or belong to a certain age group. Standard demographics might be useful, or they might be irrelevant. What are the commonalities across your customer base? Here are some examples: • A hospital management system has to think about the hospital administrator who will buy their software and the actual hospital workers who would use it • An on-call veterinarian service needs to talk to pet owners • An online marketplace for plumbers might consider plumbers on the sell side, and home owners on the buy side 34 Talking to Humans You also want to think about your early adopters. Why do they matter? Most new products ft alongside a “technology adoption curve,” as illustrated below. New founders tend to obsess about their mainstream customer (represented in the chart as the early and late majority). However, by defnition, the mainstream is waiting for proof from early adopters before they try something. If you cannot get early adopters, you cannot move on. Early adopters are usually folks who feel a pain point acutely, or love to try new products and services. In our story of Koshi and Roberta, the scientists hypothesized that their early adopter would be urban professionals in their mid to late twenties. For the three customer examples we just gave, here are examples of early adopters: • Our hospital management system might target hospital chains still stuck with an archaic vendor • Our vet service might target busy 20-somethings in a major city • Our online market for plumbers might target solo practices on the sellside and frst-time home owners on the buy-side How To 35 Tere is no prescription for how narrowly or broadly you should cast your net for customer discovery interviews. However, the more focused you can be, the easier it is to make sense of your evidence. Special Note for B2B Products If you are selling to the enterprise, you should also think about the diferent kinds of participants in your sales process. In a classic enterprise sale, you will ofen have a strategic buyer (who is excited about the change you can bring), an economic buyer (who controls the purse), a technical buyer (who might have approval/blocker rights), and then the actual users of your product. Can you identify your champion? Can you identify who might be a saboteur? For B2B companies, Steve Blank also recommends that you start by talking to mid-level managers rather than the C-suite. It can be easier to get their time, it is ofen easier to get repeat conversations, and, most importantly, it will allow you to get better educated before you go up the chain. 36 Talking to Humans What Do You Want to Learn? How To 37 Go into every customer interview with a prepared list of questions. Tis list, which we refer to as an interview guide, will keep you organized. You will appear more professional, and it will ensure that you get to your most important questions early. How do you know your most important questions? I like to begin by understanding my most important, and most risky, assumptions. Tose tend to be the areas where you need to gather insights most urgently. You can uncover your assumptions in a myriad of ways. You can use Alex Osterwalder’s business model canvas or Ash Maurya’s lean canvas. Personally, I ask these questions (see the Appendix for a worksheet and tips): • My target customer will be? • The problem my customer wants to solve is? • My customer’s need can be solved with? • Why can’t my customer solve this today? • The measurable outcome my customer wants to achieve is? • My primary customer acquisition tactic will be? • My earliest adopter will be? • I will make money (revenue) by? • My primary competition will be? • I will beat my competitors primarily because of? • My biggest risk to fnancial viability is? • My biggest technical or engineering risk is? • What assumptions do we have that, if proven wrong, would cause this business to fail? (Tip: include market size in this list) You should be able to look at this list and spot the assumptions that are both highly important and fairly uncertain. Be honest. You want to focus on the most important issues. 38 Talking to Humans In the case of our pillow entrepreneurs, they chose six initial risks which drove their research approach and frst set of questions. To give another scenario, in the last chapter we shared the example of an on-call veterinarian service. Te founders might identify a set of risks: 1. Pet owners are frustrated having to go to a vet and would rather have someone come to them 2. Customers are willing to pay a big premium to have a vet show up at their door 3. We think busy urbanite pet owners will be our early adopters 4. We think people currently discover their vets either through word of mouth or online searches 5. We can affordably acquire our customers through targeted Google search ads 6. We can recruit enough vets across the country to make this a big enough business 7. With travel baked in, our vets can see enough people in a day to be fnancially viable Not every assumption can be tested efectively through qualitative research, but in this case, our founders can probably get some insights on risks 1, 3, 4, and 6 just by talking to people. Risks 1, 3 and 4 would be focused on pet owners, while #6 would be focused on vets. Get Stories, Not Speculation When you are contemplating your questions, be careful with speculation. Humans are spectacularly bad at predicting their future behavior. It is tempting to say, “Would you like this idea?” or “Would you buy this product?” Unfortunately, you really have to treat those How To 39 answers with a great deal of skepticism. It is more efective to ask your interview subject to share a story about the past. For example, when our fctional scientists Koshi and Roberta created their interview plan, the questions were focused on getting the interviewee to tell a story about their last pillow buying experience. Keeping with our second example of an on-call vet service, the team might have a loose interview plan that looks like the following: • Warm up: concise intro on the purpose of the conversation • Warm up: basic questions about person and pet (name, age, picture) • Who is your current vet? Can you tell me about how you found and chose him/her? • Please describe the last time you had to take your pet to the vet for a checkup • Walk me through the process of scheduling a time to visit the vet. • What was frustrating about that experience? • What did you like about that experience? • Have you ever had an emergency visit to a vet? if yes, can you describe that experience for me? • Have you ever thought about changing vets? why / why not? Ask Open-Ended Questions Your goal is to talk little and get the other person sharing openly. To that end, it is imperative that you structure open-ended questions, or at minimum follow up yes/no questions with an open-ended question that gets them talking. One tip is to try to ask questions that start with words like who, what, why and how. Avoid questions that start with is, are, would, and do you. But remember, if you do get a yes/no answer to a 40 Talking to Humans question, you can always follow up in a way that gets them talking. An interesting open-ended question, which Steve Blank likes to use to conclude his interviews, is: “What should I have asked you that I didn’t?” Testing for Price Two of the hardest questions to answer through qualitative research are: will people pay? and how much will they pay? Speculative answers on this topic are extremely suspect. You can learn a lot, however, by asking questions like: • How much do you currently spend to address this problem? • What budget do you have allocated to this, and who controls it? • How much would you pay to make this problem go away? (this can lead to interesting answers as long as you don’t take answers too literally) My recommendation is to set up a situation where the subject thinks they are actually buying something, even if they know the thing doesn’t exist yet. Kickstarter and other crowdfunding platforms are used by a lot of teams to test pre-order demand. For expensive corporate products, you can also try to get customers to buy in advance or sign a non-binding letter of intent to buy. Te key thing to remember is that people don’t honestly think about willingness to pay unless they feel like it is a real transaction. Getting Feedback on a Prototype Sometimes you will want to get reactions to a product solution. You can learn a lot by putting mockups or prototypes in front of people, but, as with all speculation, you should interpret reactions with a degree of skepticism. If you show your interview subject a proposed solution, you need to separate this step from your questions about their behavior. How To 41 Ask your questions about behavior and challenges frst, so that the discussion about product features does not poison or take over the conversation. People do love talking features! The Magic Wand Question Some people like to ask, “if you could wave a magic wand and have this product do whatever you want, what would it do?” Personally, I avoid questions like this because customers are too constrained by their current reality to design efective solutions. It is the customer’s job to explain their behavior, goals, and challenges. It is the product designer’s job to come up with the best solution. Tere is one variation to the magic wand question that I do like, however, because it focuses on problems and not solutions: “If you could wave a magic wand and solve any problem, what would you want to solve?” I suspect, however, that you will fnd many people struggle with such an open question. Design “Pass/Fail” Tests Customer discovery is made up of a lot of qualitative research, but it helps to take a quantitative mindset. Set goals for key questions and track results. For example, halfway through their initial research, our scientists Koshi and Roberta already knew stats like: • 24% of shoppers knew what they wanted when they walked in • 45% of shoppers purchased a mid-priced or high-priced pillow • 68% of the shoppers we spoke to indicated that better sleep was a major driver of their choice Even better would have been if they had set targets ahead of time. For example, they might have set the following goals: • Because we are a new brand, we are hoping that most shoppers are undecided. We want to see that 40% or fewer shoppers already know what 42 Talking to Humans they want when they walk in • Because our pillow is expensive, we want to see that at least 40% of the shoppers buy mid or high-end models • Because we believe that sleep quality is a major differentiator for our product, we want over 60% of shoppers to indicate that this is a major factor in their decision making process Te numerical target you choose can be an educated guess. You do not need to stress over picking the perfect number. It is more important that you set a goal and really track what is happening. Setting a target forces you carefully think through what you are hoping to see, and makes decisions and judgment calls a bit easier as you review your data. A Guide, Not a Script An interview guide is not a script. You do not need to read from it like an automaton. You should feel free to veer of of it if the conversation brings up something interesting and new. It will likely evolve as you learn from the market and unearth new questions. But always plan, prioritize and prep your questions before any session. Observation Can Be As Powerful As Questions Sometimes the best thing you can do is sit back and watch someone’s behavior. You might watch their purchase process, or examine how they go about solving a particular problem. As you think about what you want to learn, also think through how you might gather data through observation rather than direct interviews. In our story of Koshi and Roberta, the two got some of their most valuable insights by going to linen stores and watching potential customers struggle to buy a pillow. Tey observed behavior and only then jumped in to ask questions. Tis technique cannot always be used. For example, when my How To 43 team was trying to validate a weight loss product idea, it did not feel practical to watch people go about their diet. Instead we did interviews and then put a group of customers through a two-week concierge experiment (see Glossary) where we manually acted out the diet experience. But, where possible, observing uninfuenced behavior can lead to great insights. 44 Talking to Humans How Do You Find Your Interview Subjects? How To 45 Entrepreneurs new to customer development are ofen intimidated at the thought of approaching complete strangers. It might surprise you to hear that people are ofen very willing to help out. Tis is especially true if you are working on a topic that interests them and you approach them nicely and professionally. Tere are three general rules to keep in mind when recruiting candidates to speak with: 1. Try to get one degree of separation away (don’t interview your mom, your uncle, or your best friends) 2. Be creative (and don’t expect people to come to you) 3. Fish where the fsh are (and not where they are not) Get Creative One aspiring entrepreneur wanted to target mothers of young children. She had heard stories about talking to people in a cofee shop, but felt like it was too unfocused. So she tried hanging around school pickup zones, but the moms were too busy and refused to speak to her. Next, she tried the playground, where she fgured moms would be bored watching their kids play. Tis worked reasonably well, but she was only able to get a few minutes of anyone’s time. So instead, she started organizing evening events for moms at a local spa where she bought them pedicures and wine. Te time of day worked because the moms could leave the kids at home with their partner. Te attendees had a great time and were happy to talk while they were getting their nails done. Find the Moment of Pain If you can connect with people at the moment of their theoretical pain, it can be very illuminating. My colleague Alexa Roman was working with an automotive company and they had a concept tied 46 Talking to Humans to the experience of getting gas. So Alexa and team visited a series of gas stations. Tey watched consumers go through the process of buying gas. Ten they approached them and asked questions. By thinking about the moment of pain they wanted to address, they knew exactly where to fnd their consumers and they were able to gather valuable observational research. Make Referrals Happen Use referrals to your advantage. Let’s say you want to talk to doctors. Tey are busy and have strong gatekeepers. I bet you know how to get to at least one doctor, however. Tat doctor will know other doctors. Even if your doctor happens to be a close friend and thus breaks the “more than one degree of separation” guideline, she can still give you advice on when might be a good time to talk to a doctor. She can also connect you with other doctors. You should use referrals as much as possible. Set a goal of walking out of every interview with 2 or 3 new candidates. When you end an interview, ask the person if they know others who face the problem you are trying to solve. If they feel like you have respected their time, they will ofen be willing to introduce you to others. Conferences & Meetups Conferences and meetups can be an amazing recruiting ground, because they bring a group of people with shared interests into one place. You just need to be respectful of people’s time. I have found that it is extremely efective to ask people for their time, but for later, afer the conference or meetup. Get their business card, let them get back to networking, and then have an in-depth conversation when it fts their schedule. Immediately afer the conference while their memories are still fresh, send them a short email that reminds them where you met, and give your ask for a conversation. Tis How To 47 works as efectively for in-demand panel speakers as it does for other attendees. Meetups are usually inexpensive, but conference tickets can be pricey. If you are on a budget, you can “hack” expensive conferences by intercepting people outside of the building, or, if you can get access to the attendee or speaker lists ahead of time, contacting people directly and meeting them near the event. Meetup.com has decent search tools to discover relevant events in your area, and a few good Google search queries can usually get you to a short list of conferences that ft your needs. Enterprise Customers Finding interviewees can be harder when you are focused on an enterprise customer. You need laser-like targeting. In addition to conferences, LinkedIn can be extremely useful. If you have hypotheses on the titles of the people you are seeking, run searches on LinkedIn. You might be able to get to them through a referral over LinkedIn, or you might need to cold call them through their company’s main phone number. You then have to decide on your approach method. You can either ask for advice (where you make it clear that you are not selling anything), or you can go in as if you were selling something specifc. Advice vs Selling Asking for advice should be your default method early in your customer discovery process. You will have better luck gaining access. People like being asked (it makes them feel important). Steve Blank used to call people up and say something like, “My name is Steve and [dropped name] told me you were one of the smartest people in the industry and you had really valuable advice to ofer. I’m not trying to sell you anything, but was hoping to get 20 minutes of your time.” 48 Talking to Humans Another efective spin on “asking for advice” is to create a blog focused on your problem space, and ask people if you can interview them for an article. When do you approach someone as if you were selling a product? Tis method is useful if you are past initial learning and want to test your assumptions around customer acquisition and messaging. Just don’t jump into sales mode too early. Beneftting from Gatekeepers If LinkedIn isn’t helping you and you need to reach high up in an organization, another approach is to call the CEO’s ofce. Your goal is not to talk to the CEO but actually their executive assistant. His job is to be an efective gatekeeper, so if you explain, “I’m looking to talk to the person who handles X”, they will ofen connect you to the right person (especially if you are pleasant and professional — notice the trend on that one?). Te added advantage of this method is if you end up leaving a voice mail for your intended contact, you can say “Jim from [CEO’s name]’s ofce gave me your name”. Dropping the boss’ name tends to improve response rates. Another approach is to send a targeted email into an organization with a very short email that asks for an introduction to the right person to speak to. You can make guesses as to email addresses based on LinkedIn queries. For this tactic to work, you must keep your emails extremely concise. Students and Researchers While people are willing to grant time to polite people who ask for advice, you have an extra advantage if you are a student or academic researcher. In other words, if you are a student or researcher, say so. As an extra incentive, you might also ofer to share the results of your research with your interview subjects. How To 49 You Might Be Surprised Another colleague of mine, Jonathan Irwin, was working with a Fortune 50 company. Te client team wanted to interview a special kind of oil platform engineer, of which there were less than 20 in the world! To access these people required security clearance and safety training. We challenged the team to fnd a way, expecting that they would have to rely on video conferencing or phone calls. However, the team started researching this speciality profession through Google and discovered that there was an onshore training facility just an hour away. Te moral of the story is that it ofen isn’t as hard as you think. No Fish in the Sea When I say fsh where the fsh are, it is really important to remember the fip side to that statement: don’t fsh where the fsh are not. If a method isn’t working, try something new. We were doing a project with a major magazine testing out new product ideas. Our target was busy women, and we knew that the readership correlated closely with shoppers of Te Container Store (a retail store). So we parked out front of a store and intercepted folks as they came in and out. People were willing to speak for a few minutes, but many were in a bit too much of a rush. Ten one of our teammates discovered a sample sale happening around the corner. Tere were probably 200 bored women waiting in line, most of whom were happy to talk to us to pass the time. (Note: fnding bored people stuck in line is a common recruiting hack.) Still, we didn’t feel like we were targeting quite as narrowly as we wanted (busy, working women) or as geographically broadly (we didn’t want to just talk to New Yorkers). So we turned to the magazine’s social media presence. We created a short online survey to help us qualify responses, and the magazine posted a link to their Twitter and Facebook pages with a catchy sentence. We had hundreds of women fll out the survey, and then we picked our top 50 Talking to Humans thirty candidates and scheduled calls. Online Forms & Landing Pages In a similar vein, one efective tactic is to create an online form or landing page and build up a list of people to contact. Below is an example of a landing page. Our team was testing a product idea for better home organization. Tis landing page test actually consisted of a three-step funnel with a call to action, a price choice, and then a request for an email address. We tracked the conversion metrics carefully and used the emails to schedule interviews. Caveat: driving trafc is never a trivial process. If you have budget, Google or Facebook ads can work. Otherwise, you can try to generate some word of mouth on social media or through bloggers. How To 51 Conclusion Hopefully what you are picking up through these examples is that there is no single way to get to people. It takes some creativity and hustle, but it isn’t as hard as you might think. Trust me, people will not think you are rude if you carry yourself well and act professionally. Check Out the Appendix for Examples Te Appendix has more tips and examples for cold email and voice mail approaches. 52 Talking to Humans How to Ensure an Effective Session? How To 53 I recommend the following guidelines for running a productive interview session. Do Your Interviews In Person Te quality of your learning can vary a lot depending on your communication method. Talking in person is by far the best approach. You can read body language and build rapport much easier. Remember that a huge percentage of human communication is non-verbal, so why blind your senses if you don’t have to? Te next best approach is video conferencing, because at least you can still read someone’s facial expressions. Phone calls should be your method of last resort (sometimes there is no choice), and I would entirely avoid using text-based mediums like email or chat. Talk to One Person at a Time I believe in talking to one person at a time. It is useful to have a second person on your side quietly taking notes. I strongly recommend avoiding focus groups for two reasons: 1. you want to avoid group think; 2. you will really struggle to focus on one person’s stories, and drill into areas of interest, when you are juggling multiple people. Adding a Note Taker Bringing a note taker will allow you to stay in the moment without worrying about getting every bit down on paper. You can stay focused on the topics, the body language, and where to take the conversation. If you have to take your own notes, that’s not the end of the world. It can sometimes make for a more intimate conversation. Just remember to write up your notes right afer the session or you will lose a lot of detail and color that you weren’t able to write down. You can also ask the interview subject if you can record them, 54 Talking to Humans and many people are willing. Te risk is that a recorder can inhibit the conversation, but most people forget that they are being recorded once the discussion is fowing. I highly recommend that you play back the audio and write up your notes soon afer the session, both because writing up notes will reinforce what you learned in your own mind, and also because written notes are easier and faster for both you and your teammates to scan. I’ve found that once audio or video is more than a couple weeks old, somehow they never get touched again. Start With a Warm Up & Keep It Human When you kick things of, concisely explain why you are there, and thank them for the time. Launch into things with one or two easy warm up questions. For example, if you are talking to a consumer, you might ask where they are from and what they do for a living. If you are talking to enterprise, you might ask how long they have been with their company. You don’t want to spend a lot of time on this stuf, but it does get the ball rolling. Have a written or printed list of questions, but don’t rigidly read from your list. Be in the moment. Make the interview subject feel like you are really listening to them. Disarm Your Own Biases Human beings have an amazing ability to hear what they want to hear (this is called “confrmation bias”). Go into each session prepared to hear things that you might not want to hear. Some entrepreneurs even take the mindset that they are trying to kill their idea, rather than support it, just to set the bar high and prevent themselves from leading the witness. Get Them to Tell a Story As I mentioned in the chapter “What Do You Want to Learn,” How To 55 humans are terrible at predicting their own behavior. If you ask any speculative questions, be prepared to listen with a healthy dose of skepticism. I far prefer to get people telling stories about how they experienced a problem area in the past. In particular, try to fnd out if they have tried to solve the problem. What triggered their search for a solution? How did they look for a solution? What did they think the solution would do, before they tried it? How did that particular solution work out? And if they are struggling to remember specifcs, help them set the scene of their story: what part of the year or time of day? Were you with anyone? As they are telling their story, follow up with questions about their emotional state. You might get some historical revisionism, but what you hear can be very illuminating. Te researchers at Meetup.com, who borrow from Clayton Christensen’s Jobs To Be Done framework, use an interesting tactic to help their subjects get in story mode. When they are asking someone to take them through a purchase experience, from frst thought through purchase and then actual product usage, they say: “Imagine you are flming the documentary of your life. Pretend you are flming the scene, watching the actor playing you. At this moment, what is their emotion, what are they feeling?” Look for Solution Hacks One of the best indicators that the market needs a new or better solution is that some people are not just accepting their frustration with a particular problem, but they are actively trying to solve it. Maybe they have tried a few diferent solutions. Maybe they have tried hacking together their own solution. Tese stories are a great indicator of market need. Understanding Priority For someone to try a new product, their pain usually needs to be 56 Talking to Humans acute enough that they will change their behavior, take a risk, and even pay for it. If you feel like you are seeing good evidence that someone actually has a problem, it is worth asking where it ranks in their list of things to solve. Is it their #1 pain, or something too low in priority to warrant attention and budget? Listen, Don’t Talk Try to shut up as much as possible. Try to keep your questions short and unbiased (i.e. don’t embed the answer you want to hear into the question). Don’t rush to fll the “space” when the customer pauses, because they might be thinking or have more to say. Make sure you are learning, not selling! Or, at least make sure you are not in “sales” mode until the point when you actually do try to close a sale as part of an experiment. Follow Your Nose and Drill Down Anytime something tweaks your antenna, drill down with follow up questions. Don’t be afraid to ask for clarifcations and the “why” behind the “what.” You can even try drilling into multiple layers of “why” (run an Internet search for “Five Whys” for more info), as long as the interviewee doesn’t start getting annoyed. Parrot Back or Misrepresent to Confrm For important topics, try repeating back what the person said. You can occasionally get one of two interesting results. Tey might correct you because you’ve misinterpreted what they said. Or, by hearing their own thoughts, they’ll actually realize that their true opinion is slightly diferent, and they will give you a second, more sophisticated answer. Another approach is to purposefully misrepresent what they just said when you parrot it back, and then see if they correct you. But How To 57 use this technique sparingly, if at all. Do a Dry Run If you are a beginner at customer discovery, do a dry run with a friend or colleague. See how your questions feel coming out of your mouth. Get a sense of what it is like to listen carefully and occasionally improvise. Getting Feedback on Your Product If you want to get feedback on your product ideas, whether you show simple mockups or a more polished demo, there are a few important tips to keep in mind: As I mentioned before, separate the storytelling part of your session from the feedback part. People love to brainstorm on features and solutions, and this will end up infuencing the stories they might tell. So dig into their stories frst, and gather any feedback second. Second, disarm their politeness training. People are trained not to call your baby ugly. You need to make them feel safe to do this. Ask them up-front to be brutally honest, and explain that it is the very best way for them to help you. If they seem confused, explain that the worst thing that could happen is to build something people didn’t care about. Finally, keep in mind that it is incredibly easy for people to tell you that they like your product. Don’t trust this feedback. Instead, you need to put people through an actual experience and watch their behavior or try to get them to open their wallet. Tere is no right answer on how polished your early mockups need to be. If you are in the fashion space, you need to have a high degree of visual polish as table stakes. If you are creating a solution for engineers, you probably need much less. Just don’t wait for perfection, because initial product versions rarely get everything right. You need to spot your errors sooner rather than later. 58 Talking to Humans How Do You Make Sense of What You Learn? How To 59 Your goal is not to learn for learning’s sake. Your goal is to make better decisions that increase the odds of success. So how do you translate your observations into decisions? Te frst step is to make sense of your patterns. Take Good Notes To fnd your patterns, frst you need to track the data. Tis is easy if you bring a good notetaker to the interview, but otherwise, make sure that you write up your notes as soon afer your conversation as possible. Make them available to the entire team with Google Docs or the equivalent. At the start of every entry, note the following information: • Name of interview subject • Date and time • Name of interviewer • In person or video conference • Photo (if you have one) Ten at the start of your notes, include basic descriptive information of the interview subject. Quantitative Measures If you are setting specifc metric goals for your interviews, you might set up a shared spreadsheet that essentially acts as a running scorecard for how you are doing and how you are tracking to targets. EXAMPLE Let’s imagine that you have invented a new air purifer that triples the growth speed of greenhouse plants. Now you plan to talk to 20 60 Talking to Humans farmers, and you have a few core questions: • Will their business actually beneft from increased growth speed? You are assuming that increased volume will help rather than hurt. You plan to talk to growers of different crops with the goal of fnding crops where 60% or more of farmers want increased volume. • Are farmers spending any money today on growth accelerator solutions? Your qualitative research will drill into what and why, but your metrics goal says that you hope at least 50% of the market is already spending at least some money. • Do they have the facilities to support your purifer? In this case, you need your purifer to be both in a specifc location, but also have access to an electrical outlet. You are hoping that 70% of the farmers have an outlet 20 feet or closer to your spot. Here is the kind of spreadsheet that you and your team might track: As Samantha advised Koshi and Roberta in the fctional story, turning your observations into quantifable metrics is both useful and tricky. Our brains like to infuence our thinking with cognitive biases, especially fltering results for what we want to hear. Calculating actual metrics helps fght against that dynamic. How To 61 At the same time, you have to beware a diferent kind of bias: our desire to turn statistics into facts. Hopefully you are getting enough data points that you can trust the patterns, but do not confuse this with statistical signifcance or take your results too literally. My advice is to calculate metrics, but remain skeptical of them, don’t obsess over any one particular metric, and continue to question what is behind your numbers. Dump and Sort Exercise Bring your team together and arm them with sticky notes and sharpies. Give everyone 10 minutes to jot down as many patterns and observations as they saw during their interviews. Put all the sticky notes on a wall and have someone sort them into groups. As a team, discuss the patterns, and then re-review your assumptions or business canvas and see what might need to change or require greater investigation. Look for Patterns and Apply Judgement Customer development interviews will not give you statistically signifcant data, but they will give you insights based on patterns. Tey can be very tricky to interpret, because what people say is not always what they do. You don’t want to react too strongly to any single person’s comments. You don’t want to take things too literally. But neither do you want to be bogged down trying to talk to thousands of people before you can make a decision. You need to use your judgement to read between the lines, to read body language, to try to understand context and agendas, and to flter out biases based on the types of people in your pool of interviewees. But it is exactly the ability to use human judgement based on human connections that make interviews so much more useful than surveys. Ultimately, you are better of moving fast and making decisions 62 Talking to Humans from credible patterns than dithering about in analysis paralysis. Don’t Abdicate Your Role As Product Designer It is not the job of the customer to design your product. It is yours. As you are gathering information and making decisions, act like a intelligent flter, not an order-taker. Expect False Positives While all entrepreneurs get their fair share of naysayers and skeptics, you have to be wary of the opposite problem in customer development interviews. People will want to be helpful and nice, and your brain will want to hear nice things. As you are weighing what you have learned, just keep this in mind. The Truth Curve I am a big believer in qualitative research. I think a good product team should build a regular cadence of talking to relevant people into their process. However, you don’t want your only source of learning to be talking to people. You don’t really know the absolute truth about your product until it is live and people are truly using it and you are making real money from it. But that does not mean you should jump straight to a live product, because that is a very expensive and slow way to iterate your new business. Get into the market early and begin testing your assumptions right away, starting with conversations and proceeding from there. It will dramatically increase the odds that you will create a product that customers actually want. As you build confdence, test with increasing levels of fdelity. I think of it like peeling an onion in reverse. I created the accompanying chart to demonstrate the levels of believability for diferent kinds of experiments. How To 63 Talking to people is powerful. It tends to give you your biggest leaps of insight, but, as I keep on repeating, what people say is not what they do. You might show people mockups and that might give you another level of learning and feedback, but reactions still need to be taken with skepticism. Concierge and “Wizard of Oz” experiments, where you fake the product through manual labor (see Glossary) will give you stronger evidence, because you put people through an experience and watch their actions. Te next layers of the onion are to test with a truly functional “Minimum Viable Product” (see Glossary) and beyond. Te point I want to make is that all of the steps on the curve can be very useful to help you learn, make smarter decisions, and reduce risk, but you need to use your head, and apply judgement to everything you are learning. 64 Talking to Humans How many people to talk to? Tere is no pat answer to this question. A consumer business should talk to an order of magnitude more people than a business that sells to enterprise. If you are in the consumer space and haven’t spoken to at least 50 to 100 people, you probably have not done enough research. In his I-Corps course, Steve Blank requires his teams, many of which are B2B, to talk to at least 100 people over 7 weeks. I advise that you never stop talking to potential customers, but you will probably evolve what you seek to learn. If you see the same patterns over and over again, you might change things up and examine diferent assumptions and risks. For example, if you feel like you have a frm understanding of your customer’s true need, you might move on to exploring how they learn about and purchase solutions in your product category today. And don’t forget that observing your customers can be as powerful as directly talking to them. Lead with Vision Customer Development and lean startup techniques are some of the most powerful ways to increase your odds of success, but they are not a replacement for vision. You need to start with vision. You need to start with how you want to improve the world and add value to people’s lives. Te techniques we’ve discussed in this book are among a body of techniques that let you reality check your vision, and optimize the path you will take to achieve your vision. How To 65 Conclusion Toughtful qualitative research is a critical tool for any entrepreneur. Hopefully this book has given you some new strategies for how to put it to work for your needs. Creating a new business is tremendously challenging. Te ways you can fail are numerous. t
You have to get the customer and market right t
You have to get the revenue model right t
You have to get the cost structure right t
You have to get customer acquisition right t
You have to get the product right t
You have to get the team right t
You have to get your timing right Screw up any one of those and you are toast. Tere is a reason why entrepreneurship is not for the faint of heart. But we’re not here to be faint of heart. We are here to change the world. Dream big. Be passionate. Just be ruthless with your ideas and assumptions. Customer discovery and lean experimentation can truly help you chart a better path and fnd success faster and with more capital efciency. Don’t forget that as your business grows and changes, so too will your customer base. Keep on reality-checking your hypotheses. Keep on talking to humans. Appendix PART THREE Appendix 67 Cold Approach Examples When you are trying to reach someone you do not know, there are a few things to remember: 1. Keep things concise 2. Keep things convenient (meet near their ofce, etc) 3. Name drop when you can 4. Follow up if you don’t hear an answer, but don’t be annoying 5. If you are leaving a voice mail, practice it frst (you might think it sounds practiced, but to others, it will sound more professional) Example Email 1 To: [email protected] From: [email protected] John, I received your name from James Smith. He said that you had a lot of expertise in an area I am researching and recommended that we speak. I’m trying to study how companies are handling their expense report management workfows and the frustrations they are experiencing. I would be happy to share my research conclusions with you. Would you have 30 minutes to spare next week when I could buy you a cup of coffee and ask you a few questions? Many thanks for your time and I look forward to hearing from you, Jane Doe 68 Talking to Humans Example Email 2 To: [email protected] From: [email protected] John, I have been working on some new solutions in the area of expense report management, and I was told that you have a lot of expertise in this area. We started this journey because of personal frustration, and we’re trying to fgure out how to make expense reporting much less painful. Would you have 30 minutes to give us some advice, and share some of your experiences in this domain? I assure you that I’m not selling anything. I would be happy to come by your offce or arrange a quick video conference, at your preference. Many thanks, Jane Doe Example Voice Mail Message “Hello, my name is Jane Doe. I was referred to you by James Smith, who said I would beneft from your advice. I am currently researching how companies are handling their expense management workfows. I understand you have a lot of expertise in this area. I was hoping to take just 30 minutes of your time to ask you a few questions. I’m not selling anything and I would be happy to share my research conclusions with you. You can reach me at 555-555-5555. Again, this is Jane Doe, at 555-555-5555, and thank you for your time.” Final Note Cold calling is never anyone’s favorite thing to do, but it isn’t nearly as painful as you imagine. You have nothing to lose and everything to gain. So give yourself a determined smile in the mirror, and go get them! Appendix 69 Business Assumptions Exercise I am agnostic about the framework you choose to use to map out your business assumptions. Alexander Osterwalder’s business model canvas and Ash Maurya’s lean canvas are both powerful tools. I also ofen fnd myself using this simple set of questions to lay out a belief system around an idea: Try to make your assumptions as concise and specifc as possible. You want to be able to run an experiment against it to see if it is true. My target customer will be? (Tip: how would you describe your primary target customer) The problem my customer wants to solve is? (Tip: what does your customer struggle with or what need do they want to fulfll) My customer’s need can be solved with? (Tip: give a very concise description / elevator pitch of your product) Why can’t my customer solve this today? (Tip: what are the obstacles that have prevented my customer from solving this already) The measurable outcome my customer wants to achieve is? (Tip: what measurable change in your your customer’s life makes them love your product) 70 Talking to Humans My primary customer acquisition tactic will be? (Tip: you will likely have multiple marketing channels, but there is often one method, at most two, that dominates your customer acquisition — what is your current guess) My earliest adopter will be? (Tip: remember that you can’t get to the mainstream customer without getting early adopters frst) I will make money (revenue) by? (Tip: don’t list all the ideas for making money, but pick your primary one) My primary competition will be? (Tip: think about both direct and indirect competition) I will beat my competitors primarily because of? (Tip: what truly differentiates you from the competition?) My biggest risk to fnancial viability is? (Tip: what could prevent you from getting to breakeven? is there something baked into your revenue or cost model that you can de-risk?) My biggest technical or engineering risk is? (Tip: is there a major technical challenge that might hinder building your product?) And then answer the following open-ended question. Be creative and really examine your points of failure. Appendix 71 What assumptions do we have that, if proven wrong, would cause this business to fail? 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Afer you have looked at your business holistically and also answered the broad fnal question, mark the assumptions that would have a large impact on your business and feel highly uncertain. Now you know your priorities for customer discovery and the experiments you need to run! 72 Talking to Humans Teaching Exercise #1: Mock Interviews If you are using this book to try to teach customer discovery/ development, there is nothing like real-world practice to make learning stick. Before you send your class out into the world to conduct their own interviews, however, you might try a compact exercise like the following: Tools All participants should have pen and paper Preface: Choose a Topic Everyone in the class will interview each other based on the same topic, which means it needs to be something most people can relate two. Tere are two angles you might take: 1. Something that helps the interviewer dig up past behavior. For example, “Tell me about the last thing you purchased over $100.” Have the interview subject explain what they bought, what the purchase process was like from desire to actual ownership, how they made their purchase decision, etc. 2. Something that helps the interviewer unlock deeper motivations and desires. For example, “Tell me about your dream car.” Prompt your students not just to get people to describe the car, but to dig into the reasons behind the choice; they can also prompt for whether the interview subject has ever experienced driving the car. Appendix 73 Exercise Step 1: Intro, 5 minutes Explain the exercise, the topic that the students will use, and give a few specifc suggestions for questions they might ask. Example questions for the dream car: when did you fall in love with the car and why? of the reasons you shared, why are these the most important to you? how have you imagined using the car? etc Step 2: Interview Plan, 2 minutes Give your class the topic and let them spend 5 minutes on their own. Tey should write down no more than 6 questions to ask. Step 3: Pair Interviews, 5 - 7 minutes each Pair up your students. One will begin as the interviewer, and their opposite will be interviewed. Give them 7 minutes, and then switch the roles, keeping the pairs unchanged. Te new interviewer gets 7 minutes. Te person doing the interviewing should also take notes, which will give them some exposure to doing an interview solo as opposed to bringing a note-taker to help (which is what most people prefer to do when possible). Step 4: Observations and Questions, 5-10 minutes Ask the room to share observations, challenges, lessons or questions on what it was like to do a live interview. 74 Talking to Humans Teaching Exercise #2: Mock Approach Dean Chang, the Associate VP of Entrepreneurship at the University of Maryland, recommends a class exercise where one or more teams of students takes on the role of cold calling an “expert.” Te team has to do it over and over until they get it right. For this exercise, select one team and have them come to the front of the classroom. Teir job is to “cold call” a selected member of the teaching team. Te teacher will pretend to be an expert in the team’s target feld. Te team needs to get the expert to take the call, and smoothly transition into asking questions. Te job of the person playing the “expert” is to block the team’s misguided attempts to engage. When the team does something wrong, the expert declines the interview request, or ends the conversation, or gives them a gong. Ten the team has to start over again. Classic mistakes that should trigger the team starting over include long or unclear introductions, pitching the product/technology too soon, implying that the expert has problems and desperately needs help, and/or generally making the expert feel uncomfortable with the line of questioning. As Dean describes it, “We let the other teams ofer critiques and suggest plans of attack for winning over the expert and then the chosen team tries it again. Eventually afer being gonged several times in a row, they stop making the same mistakes and start to Appendix 75 converge on a good elevator pitch that praises and disarms the expert and paves the way to entering into an interview. Ten we stop the exercise.” Te exercise will probably be humorous and painful at the same time, but there is nothing like stumbling, or watching a team stumble, to realize why best practices are best practices. 76 Talking to Humans Screwing Up Customer Discovery So how do people screw up customer discovery? Here are a few antipatterns: 1. You treat speculation as confrmation Here are some question types that I don’t like — and if you ask them, you should heavily discount the answer: “would you use this?” “would you pay for this?” “would you like this?” I can’t say that I never ask these questions, but I always prefer behavioral questions over speculation. As contrast, here is a behavior-focused interaction: “Tell me about a time when you bought airline tickets online.” “What did you enjoy about the process? What frustrated you about the process?” “What diferent systems or methods have you tried in the past to book tickets?” 2. You lead the witness Leading the witness is putting the answer in the interviewee’s mouth in the way you ask the question. For example: “We don’t think most people really want to book tickets online, but what do you think?” Examine both how you phrase your questions and your tone of voice. Are you steering the answer? Ask open-ended, neutral questions before you drill down: “what was that experience of buying online tickets like?” 3. You just can’t stop talking Some entrepreneurs can’t help themselves — they are overfowing with excitement and just have to pitch pitch pitch. Tere is nothing Appendix 77 wrong with trying to pre-sell your product — that is an interesting experiment unto itself — but you should not mix this in with behavioral learning. If you do try to pre-sell, don’t just ask, “Would you pay for this?” but rather ask them to actually pay, and see what happens. Some people ask the question, “How much would you pay for this?” but I do not. Instead, try actually selling at diferent price points (albeit one at a time). I much prefer having the potential customer experience something, rather than speculate over something. 4. You only hear what you want to hear I see some people go into interviews with strong beliefs about what they like and dislike. When you debrief afer their custdev conversation, it is magical how everything they heard aligns perfectly with their opinions. Our brains are amazing flters. Leave your agenda at the door before starting a conversation. One way to solve this is to have two people for each interview — one person to ask questions, and the other to take notes. 5. You treat a single conversation as ultimate truth You’ve just spoken to a potential customer and they have really strong opinions. One instinct is to jump to conclusions and rush to make changes. Instead, you need to be patient. Tere is no defnitive answer for how many similar answers equals the truth. Look for patterns and use your judgement. A clear, consistent pattern at even 5 or 10 people is a signal. 6. Fear of rejection wins out Tis is one of the biggest blockers to people doing qualitative research, in my experience, because of fear of a stranger rejecting your advance or rejecting your idea. Many excuses, such as “I don’t know how to fnd people to talk to,” are rooted in this fear. JFDI. Customer development isn’t just about street intercepts. You can 78 Talking to Humans recruit people on Craigslist, Facebook and LinkedIn groups, and good old fashioned networking. 7. You talk to anyone with a pulse I see some teams taking a shotgun approach. Instead, defne your assumptions around who your customer will be and who your early adopter will be. You might even do a lightweight persona (see the book Lean UX for examples). Zoom in on those people and try to validate or invalidate your assumptions about your customers. It is ok to occasionally go outside your target zone for learning, but don’t boil the ocean. Focus, learn, and pivot if necessary. 8. You wing the conversation If you go into a conversation unprepared, it will be evident. Write up your questions ahead of time and force-rank them based on the risks and assumptions you are worried about. To defne your assumptions, you can answer the questions in the business assumptions exercise (previous section), or do a business model canvas or a lean canvas. Your exact method doesn’t matter as much as the act of prioritizing your risk areas. During your actual interview, do not literally read your questions from a piece of paper, but rather keep things conversational (remember, you are getting the subject to tell you stories). If you uncover something interesting, follow your nose and don’t be afraid to diverge from your initial priorities. 9. You try to learn everything in one sitting Rather than trying to go as broad as possible in every conversation, you are actually better of zooming in on a few areas which are critical to your business. If you have a huge range of questions, do more interviews and split the questions. Appendix 79 10. Only the designer does qualitative research It is ok to divide and conquer most of the time, but everyone on the team should be forced to get out and talk to real people. Note: you will probably have to coach newcomers on #5’s point about not jumping to conclusions. 11. You did customer development your frst week, but haven’t felt a need to do it since It is always sad to see product teams start things of with customer development, and then completely stop once they get going. It is perfectly fne to let customer discovery work ebb and fow. If your learning curve fattens, it can make sense to press pause or change up your approach. However, you want to build a regular qualitative cadence into your product process. It will provide a necessary complement to your quantitative metrics, because it will help you understand the reasons why things are happening. 12. You ask the customer to design your product for you Tere’s a famous line attributed to Henry Ford, “If I had asked people what they wanted, they would have said faster horses.” Remember, it is not the customer’s job to design the solution. It is your job. It is the customer’s job to tell you if your solution sucks. Get feedback, yes. Remember that the further away you are from a working product, the more you have to flter what you hear through your judgement and vision. Disclaimer As with all tips on lean and agile, there are always places and times to break the rules and do what is right for your context, and your business. 80 Talking to Humans Glossary Concierge and “Wizard of Oz” Experiments A concierge experiment is where you manually act out your product. An example in Eric Ries’ book Te Lean Startup shows an entrepreneur serving as a personal shopper for people before trying to design an automated solution. When my colleagues were testing a diet plan service, we did not want to rush to sofware before testing our assumptions. Instead, we interviewed participants about their food preferences, manually created meal plans which were emailed to them over two weeks, and interviewed them at various points in the process. At the end of the two weeks, we asked them to pay a set amount to continue, and tracked the conversion rate. A “Wizard of Oz” experiment is similar, with the diference being that the manual work is hidden from the customer. For example, another set of colleagues tested an idea for a smart task management system for married couples. Te twenty couples participating in the test thought that they were interacting with a computer system, but in reality they were emailing in to our team, who then processed the emails accordingly. We just said that the servers would be “down” at night! Minimum Viable Product (MVP) An MVP is the smallest thing you can create that gives you meaningful learning about your product. MVP is ofen used interchangeably with “experiment” in the broader community. I personally tend to reserve it specifcally for tests around the product, and not for experiments related to other business assumptions. It is best to think about MVPs as an ongoing process, rather than a single release. Validation is rarely that neat and tidy. Appendix 81 Scientifc Method I think the best way to explain the scientifc method is to quote the theoretical physicist, Richard Feynman: “In general we look for a new law by the following process: frst we guess it. Don’t laugh -- that’s really true. Ten we compute the consequences of the guess to see what, if this law is right, what it would imply. Ten we compare those computation results to nature, i.e. experiment and experience. We compare it directly to observation to see if it works. “If it disagrees with experiment, it’s wrong. Tat simple statement is the key to science. It doesn’t make a diference how beautiful your guess is, it doesn’t make a diference how smart you are, who made the guess or what his name is -- if it disagrees with experiment, it’s wrong. Tat’s all there is to it.” (Cornell lecture, 1964) It is relatively straightforward to apply the scientifc method to business. You accept that your ideas are hypotheses. You make them as specifc as possible so that you can guess the results, i.e. the implications, of your hypotheses. You design and run an experiment. If your hypothesized results do not match the results of your experiment, your hypothesis is proven wrong. However, business is about people, and people are highly complex and inconsistent compared to laws of nature. So if your experiment fails, you will still need to apply judgement about whether the errors are in the hypothesis or in the experiment. 82 Talking to Humans Other Learning Resources Authors Te two seminal books on the topics of lean innovation and customer development are Steve Blank and Bob Dorf ’s Te Startup Owner’s Manual and Eric Ries’ Te Lean Startup. Tere are a ton of other resources out there, from books to videos and blog posts. Rather than link to particular items and thus miss out on newer developments, here are a few names that I recommend you pay attention to: Alex Osterwalder, Alistair Croll, Ash Maurya, Ben Yoskowitz, Brant Cooper, Cindy Alvarez, David Bland, Jef Gothelf, Joel Gascoigne, Josh Seiden, Kevin Dewalt, Laura Klein, Patrick Vlaskovits, Rob Fitzpatrick, Salim Virani, and Tristan Kromer. Talking to Humans Website On our website talkingtohumans.com, you can get worksheet pdfs and sign up for our email list, where we send occasional notes based on useful resources we discover. Behind the Book 83 Gif Constable (gifconstable.com) is a repeat entrepreneur and currently the CEO of Neo, a global product innovation consulting company. He has held product design and business roles in six startups, and provided M&A and IPO services to technology frms while at Broadview/Jeferies. He was one of the earliest adopters & bloggers of the Lean Startup movement, co-organizes the 4,700-person Lean Lessons Learned meetup in New York, and tries to give back to the entrepreneurial community through mentoring and speaking engagements. He lives outside of New York City with his wife, two children, and an excessively rambunctious retriever. Giff Constable Talking to Humans was written by Gif Constable, at the instigation and with the collaboration of Frank Rimalovski of NYU’s Entrepreneurial Institute, and with the wonderful illustrations of Tom Fishburne. Behind the Book 84 Guide to Customer Discovery Frank Rimalovski brings over 20 years of experience in technology commercialization, startups and early-stage venture capital investing. He is executive director of the NYU Entrepreneurial Institute, managing director of the NYU Innovation Venture Fund, Adjunct Faculty at NYU’s Polytechnic School of Engineering, and an Instructor in the NSF’s I-Corps program, having trained and mentored hundreds of entrepreneurs in customer development and lean startup methodologies. Previously, he was a founding partner of New Venture Partners, director/entrepreneur-in-residence at Lucent’s New Ventures Group, and has held various positions in product management, marketing and business development at Sun Microsystems, Apple and NeXT. He lives outside of New York City with his wife, two daughters and his increasingly mellow mutt. Frank Rimalovski Tom Fishburne (marketoonist.com) started drawing cartoons on the backs of Harvard Business School cases. His cartoons have grown by word of mouth to reach 100,000 business readers a week and have been featured by the Wall Street Journal, Fast Company, and the New York Times. Tom is the Founder and CEO of Marketoon Studios, a content marketing studio that helps businesses such as Google, Kronos, and Rocketfuel reach their audiences with cartoons. Tom draws from 19 years in the marketing and innovation trenches at Method Products, Nestle, and General Mills. He lives near San Francisco with his wife and two daughters. Tom Fishburne Behind the Book 85 Like The Book? When Frank approached me to write this book, we both had the same goal of giving back to the community. We debated charging for the book, and pondered whether the question of free versus paid would afect how it was perceived. But ultimately, we decided to put it out into the world for free. Should you like Talking to Humans, and feel a need to contribute back to something, we would encourage you to think about doing one or all of the following: 1. Pay it back (and forward!) by mentoring another student or entrepreneur 2. Donate to one of our favorite causes: Charity: Water, Girls Who Code, Kiva or the NYU Entrepreneurial Institute 3. Share a link to the talkingtohumans.com website or give someone a copy of the book If this book has helped you in some small way, then that is reward enough for us. It’s why we did it. Gif Constable and Frank Rimalovski September 2014 talkingtohumans.com page intentionally blank Acclaim for Talking to Humans “Talking to Humans is the perfect complement to the existing body of work on customer development. If you are teaching entrepreneurship or running a startup accelerator, you need to make it required reading for your students and teams. I have.” Steve Blank, entrepreneur and author of The Startup Owner’s Manual “Getting started on your Customer Discovery journey is the most important step to becoming a successful entrepreneur and reading Talking To Humans is the smartest frst step to fnding and solving real problems for paying customers.” Andre Marquis, Executive Director, Lester Center for Entrepreneurship, University of California Berkeley “If entrepreneurship 101 is talking to customers, this is the syllabus. Talking to Humans is a thoughtful guide to the customer informed product development that lies at the foundation of successful start-ups.” Phin Barnes, Partner, First Round Capital “A lot of entrepreneurs pay lip service to talking to customers but you have to know how. Talking to Humans ofers concrete examples on how to how to recruit candidates, how to conduct interviews, and how to prioritize learning from customers more through listening versus talking.” Ash Maurya, Founder of Spark59 and author of Running Lean “When getting ‘out of the building,’ too many people crash and burn right out of the gate and wonder what happened. Talking to Humans is a quick and efective guide for how Lean Startup interviews should be done.” Dean Chang, Associate VP for Innovation & Entrepreneurship, University of Maryland #talkingtohumans talkingtohumans.com

I'm providing you with your source material. You will not be using any outside material. Your job is to answer questions about the material. What are the essential steps and key points from the customer discovery process outlined in "Talking to Humans"? TALKING TO HUMANS Success starts with understanding your customers GIFF CONSTABLE with Frank Rimalovski illustrations by Tom Fishburne and foreword by Steve Blank Copyright ©2014 Gif Constable First edition, v1.71 All rights reserved. Book design: Gif Constable Illustrations by Tom Fishburne Cover design assistance: Jono Mallanyk Lean Startup is trademarked by Eric Ries Customer Discovery is a phrase coined by Steve Blank ISBN: 978-0-9908009-0-3 Special thanks to the NYU Entrepreneurial Institute for their collaboration and support in the creation of Talking to Humans Acclaim for Talking to Humans “If you are teaching entrepreneurship or running a startup accelerator, you need to make it required reading for your students and teams. I have.” Steve Blank, entrepreneur, educator and author of Four Steps to the Epiphany and The Startup Owner’s Manual “If entrepreneurship 101 is talking to customers, this is the syllabus. Talking to Humans is a thoughtful guide to the customer informed product development that lies at the foundation of successful start-ups.” Phin Barnes, Partner, First Round Capital “Getting started on your Customer Discovery journey is the most important step to becoming a successful entrepreneur and reading Talking To Humans is the smartest frst step to fnding and solving real problems for paying customers.” Andre Marquis, Executive Director, Lester Center for Entrepreneurship University of California Berkeley “A lot of entrepreneurs pay lip service to talking to customers but you have to know how. Talking to Humans ofers concrete examples on how to how to recruit candidates, how to conduct interviews, and how to prioritize learning from customers more through listening versus talking.” Ash Maurya, Founder Spark59 and Author of Running Lean “Tis is a great how-to guide for entrepreneurs that provides practical guidance and examples on one of the most important and ofen under practiced requirements of building a great startup—getting out of the ofce, talking directly with customers and partners, and beginning the critical process of building a community.” David Aronoff, General Partner, Flybridge Capital “Gif has been one of the thought leaders in the lean startup movement from the very beginning. Entrepreneurs in all industries will fnd Talking to Humans practical, insightful, and incredibly useful.” Patrick Vlaskovits, New York Times bestselling author of The Lean Entpreneur “Current and future customers are the best source of feedback and insight for your new product ideas. Talking to them is intimidating and seemingly time-consuming. In this focused, practical, down-to-earth book Gif Constable demystifes the art (not science) of customer discovery helping entrepreneurs and product veterans alike learn how to build a continuous conversation with their market and ensure the best chances of success for their ideas. Want to know what your audience is thinking? Read this book!” Jeff Gothelf, author of LeanUX “When getting ‘out of the building,’ too many people crash and burn right out of the gate and wonder what happened. Talking to Humans is a quick and efective guide for how Lean Startup interviews should be done: who to talk to, how to talk your way in the door, and how to gain the most insight and learning. Don’t crash and burn – read Talking to Humans!” Dean Chang, Associate Vice President for Innovation & Entrepreneurship University of Maryland “A must read for anyone who is considering creating a startup, developing a new product or starting a new division. Read this book frst – a great guide to the evolving art of customer discovery. Don’t waste your time building products that your customer may or may not want. Before you write the frst line of code, pitch your idea to investors or build the frst prototype, do your self a favor, read this book and follow the advice! I guarantee you will make better decisions, build a better product and have a more successful company.” John Burke, Partner, True Ventures “Primary market research has been around for a long time because it has stood the test of time and proved that it is fundamental to building a successful venture; it underlies all that we do at MIT in entrepreneurship. Te question is how we more broadly deployed appropriate skills to entrepreneurs so they can be guided to do this in an efcient and efective manner while maintaining rigor. With all the sloganeering out there on the topic, this book stands out in that it delivers real value to the practitioner in this regard.” Bill Aulet, Managing Director, Martin Trust Center for MIT Entrepreneurship “Talking to strangers can be scary, but it’s vital to launching any new product. Trough storytelling, Gif Constable makes customer development concepts accessible. Tis book will show you how to articulate assumptions, get useful information and turn it into meaningful insights. Ten it delivers practical advice you can use immediately to test your ideas. Fear holds people back. Tis book will give you the confdence to jump.” Andres Glusman, Chief Strategy Offcer, Meetup.com Table of Contents 8 Foreword 11 Introduction 14 The Story 28 Lessons Learned 30 How To 31 Getting Started with Customer Discovery 32 Who Do You Want to Learn From? 36 What Do You Want to Learn? 44 How Do You Find Your Interview Subjects? 52 How to Ensure an Effective Session? 58 How Do You Make Sense of What You Learn? 65 Conclusion 66 Appendix 67 Cold Approach Examples 69 Business Assumptions Exercise 72 Teaching Exercise #1: Mock Interviews 74 Teaching Exercise #2: Mock Approach 76 Screwing Up Customer Discovery 80 Glossary 82 Other Learning Resources 83 Behind the Book 8 Talking to Humans Foreword “Get out of the building!” Tat’s been the key lesson in building startups since I frst started teaching customer development and the Lean Launchpad curriculum in 2002. Since then, a lot has happened. Te concepts I frst outlined in my book Te Four Steps to the Epiphany have grown into an international movement: Te Lean Startup. Te class I developed - Te Lean Launchpad - is now taught at Stanford, UC Berkeley, Columbia University, UCSF, and most recently New York University (NYU). More than 200 college and university faculty have taken my Lean Launchpad Educators Seminar, and have gone on to teach the curriculum at hundreds of universities around the globe. Te National Science Foundation, and now the National Institute of Health, use it to commercialize scientifc research as part of their Innovation Corps (I-Corps) program. My How to Build a Startup class on Udacity has been viewed by over 225,000 students worldwide. During the past few years, we’ve seen dozens of large companies including General Electric, Qualcomm and Intuit begin to adopt the lean startup methodology. Te Lean Startup turns the decades-old formula of writing a business plan, pitching it to investors, assembling a team, and launching and selling a product on its head. While terms like “pivot” and “minimum viable product” have become widely used, they are not understood by many. Te same can be said of “getting out of the building”. Many entrepreneurs “get out” and get in front of customers, but take a simplistic view and ask their customers what they want, or if they would buy their startup’s (half-baked) product. Te “getting out” part is easy. It is the application of the customer Foreword & Introduction 9 development methodology and the testing of their hypotheses with users, customers and partners that is both critical and ofen difcult for entrepreneurs to grasp in the search for a scalable and repeatable business model. Since the Four Steps, many other books have been written on customer development including Te Startup Owner’s Manual, Business Model Generation, Te Lean Startup, and others. Each of these texts has advanced our understanding of the customer development methodology in one way or another, teaching aspiring students and entrepreneurs the what, when and why we should get out of the building, but have only skimmed the surface on “how” to get out of the building. For both my own classes as well as I-Corps, I always made Gif Constable’s blog post “12 Tips for Early Customer Development Interviews” required reading. It answered the “how” question as well. Now Gif has turned those 12 tips into an entire book of great advice. In a comprehensive, yet concise and accessible manner, Talking to Humans teaches you how to get out of the building. It guides students and entrepreneurs through the critical elements: how to fnd interview candidates, structure and conduct efective interviews and synthesize your learning. Gif provides ample anecdotes as well as useful strategies, tactics and best practices to help you hit the ground running in your customer discovery interviews. If you are a student, aspiring entrepreneur or product manager trying to bring the value of getting out of the building to an existing company, Talking to Humans is a must read. It is chock full of lessons learned and actionable advice that will enable you to make the most of your time out of the building. Talking to Humans is the perfect complement to the existing 10 Talking to Humans body of work on customer development. If you are teaching entrepreneurship or running a startup accelerator, you need to make it required reading for your students and teams. I have. Steve Blank September 3, 2014 Foreword & Introduction 11 Introduction 12 Talking to Humans Te art of being a great entrepreneur is fnding the right balance between vision and reality. You are probably opening this book because you want to put something new in the world. Tat’s an incredibly powerful and meaningful endeavor. It’s also scary and extremely risky. How can you get ahead of that risk and beat the odds? Every new business idea is built upon a stack of assumptions. We agree with Steve Blank’s insight that it is better to challenge your risky assumptions right at the start. You can’t challenge anything sitting in a conference room. You have to get into the market, or, as Blank likes to say, “Get out of the building!” Tere are two efective ways to do this: 1. talk directly to your customers and partners, and observe their behavior; 2. run experiments in which you put people through an experience and track what happens. Tis book focuses on the frst. Te qualitative part of customer discovery is surprisingly hard for most people, partly because talking to strangers can feel intimidating, and partially because our instincts on how to do it are ofen wrong. Here’s what customer discovery is not: It is not asking people to design your product for you. It is not about abdicating your vision. It is also not about pitching. A natural tendency is to try to sell other people on your idea, but your job in customer discovery is to learn. You are a detective. You are looking for clues that help confrm or deny your assumptions. Whether you are a tiny startup or an intrapreneurial team within a big company, your goal is not to compile statistically signifcant answers. Instead you want to look for patterns that will help you make better decisions. Tose decisions should lead to action, and smart action is what you need for success. Foreword & Introduction 13 Tis book was written as a focused primer on qualitative research to help you get started. You should view it as a complement to the other excellent resources out there on customer development and lean innovation. It is not a rulebook, but hopefully you will fnd the principles included here useful. Te book comes in two parts. It begins with a fctional story of two entrepreneurs doing customer research for the frst time. Te second part is a mix of theory and tactics to guide you through the core steps of customer discovery. While the fctional story highlights a consumer-facing business, I should note that there are plenty of tips in this book for teams who sell to the enterprise. Some last words to kick things of: entrepreneurs have a tendency to over-obsess about their product to the neglect of other business risks. Tey also tend to stay inside their heads for far too long. I urge you to be brave, get out of the building, and go talk to real human beings. Gif Constable August 2014 Some Thanks Are Due Many thanks to Frank Rimalovski for encouraging me to write this, and his students and team at NYU for providing early feedback, Steve Blank for the foreword and his inspiration and leadership on the topic of entrepreneurship, Tom Fishburne for his great illustrations, Josh Seiden and Jef Gothelf for their insights, my colleagues at Neo for continuing to push forward the craf of customer development, the many speakers and members of New York’s Lean Lessons Learned meetup who have shared their stories with me, and Eric Ries for inspiring me and so many others. The Story PART ONE The Story 15 Breakthrough Koshi and Roberta had so much adrenaline pumping through their systems that neither could sleep that night. Afer a year of challenging lab work, they had fnally cracked it. Tey were now sure they could manufacture artifcial down feathers cost-efectively. Teir insomnia was ironic, since their very dream was to transform the quality of people’s sleep through the invention of a better pillow. Tey knew they had a technical advantage. Teir artifcial down had heightened levels of insulation, a better resilience/resistance quotient, and was kinder to both animals and the environment. Now the question was, did they have a business? The Advisor Tey called a meeting with their entrepreneurial advisor the next day. Samantha had built four companies, successfully exiting two of them. She was now an angel investor and believed frmly in giving back by working with frst-time entrepreneurs. “We fnally cracked it!” Roberta blurted out. “What she means,” Koshi said, “is that we’re convinced we can manufacture NewDown in a cost-efective and repeatable manner. Now we think we can make a real business.” “So you want to know if the time has come to jump in feet frst?” asked Samantha. Te two scientists nodded. “If you want to be successful bringing something to market, you need to understand the market. Do you feel like you know when and why people buy pillows today?” “Not really,” Roberta said. “We’ve spent our time in the lab focused on the product side.” “I suspected so. Founders commonly obsess about product at the 16 Talking to Humans expense of the understanding the customer or the business model. You need to work on it all, and you have to challenge your thinking. Behind your startup is a belief system about how your business will work. Some of your assumptions will be right, but the ones that are wrong could crater your business. I want you to get ahead of the risky hypotheses that might cause failure.” Samantha had the founders list out the riskiest hypotheses. 1. We believe that people care about sleep quality when making a pillow purchase decision. 2. We believe that we can sell online directly to customers. 3. We believe that our customers will be young urban professionals. 4. We believe that our very frst customers will be new graduates who need to outft their apartments. 5. We believe that we can sell our pillows at a high enough price to cover our costs. 6. We believe that we can raise enough capital to cover investments in manufacturing. “Let’s put aside the fundraising risk right now,” Samantha said. “It’s what everyone jumps to, but you need to strengthen your story frst. Many of your risks are tied to your customer. I like attacking a problem from multiple directions and recommend three approaches. First, I want you to walk a day in your customer’s shoes and actually go out and buy a pillow. Second, I want you to observe people in the process of buying a pillow. And third, I want you to talk directly to them.” “Talk to people?” said Koshi. “I’m a scientist, not a salesperson. If I simply asked someone if my pillow was better, they would have no idea. If I asked them if they would buy my pillow, I couldn’t trust The Story 17 the answer. So what is the point?” “Your job right now isn’t to sell, but rather to learn. You are right, though: getting the customer to speculate is rarely useful,” Samantha said. “You need to understand your market. How does your customer buy? When do they buy? Why do they buy? Where do they buy? As a scientist, you are fully capable of doing research, gathering data, and seeing if your data supports your hypotheses. I promise you, if you are polite and creative, people will be more receptive to you than you might think.” “Buying. Observing. Talking. Do we really need to do all three? Can we really aford to spend the time?” “Can you aford not to? Each of the three approaches is imperfect, but together you should see patterns. By walking in your customer’s shoes you will gain empathy and personal understanding, but you don’t want to rely solely on your own experience. By watching people shop, you can witness honest behavior, but you won’t be able to get into their heads to know their motivations. By talking to people, you gather intel on both behavior and motivation, but you have to be careful not to take what you hear too literally. Each method has strengths and weaknesses, but taken together you will learn a ton. You will have a lot more confdence that you are either on the right track, or that you have to make changes to your plans. It is far better to discover bad assumptions now, before you have invested a lot! Now, how do you think you should proceed?” “We want our customers to buy online from us, so I guess we should also buy our own pillow online,” said Roberta. “And we can observe people shopping by going to a home goods store.” “Tat sounds good,” said Samantha. “You will want to talk to some of those people in the store as well. I see one catch: you will be 18 Talking to Humans targeting the moment of purchase but not the type of customer you are hoping for. One of your risk assumptions was specifcally about young urban professionals and new graduates, so what can you also do to target and connect with them?” “What about going to a cofee shop near the downtown ofce buildings as people are going to work?” Koshi said. “Can’t we just hit up some of the people we used to know in college who are now in the working world?” Roberta said. “Why don’t you try both, and see which approach works better,” said Samantha. “Roberta, I would also ask your friends if they will refer you to their friends. It’s best to talk to people who aren’t too close to you. You don’t want a someone’s afection for you to steer what they have to say. “Let’s start by thinking through the questions you want to ask. It always makes sense to prioritize what you want to learn. You should write down an interview plan, even if you don’t completely stick to it. Break the ice, and then get them to tell you a story about buying a pillow!” Te scientists sketched out a plan: Intro: hello, I’m a PhD candidate at Hillside University and I’m researching sleep quality. I’m asking people about the last time they bought a pillow. Would you mind if I asked a few questions? When was the last time you bought a pillow? Why did you go looking for a pillow? How did you start shopping for a pillow? Why did you choose the one you bought? After you bought, how did you feel about the pillow you purchased? The Story 19 Are you going to be in the market for a pillow anytime soon? “Tat’s a great start,” Samantha said. “Keep good notes as you go, and remember to regularly regroup to review your fndings and look for patterns. Be mindful of which method you used as you discuss your observations.” Walking in the Customer’s Shoes Koshi and Roberta got together the next day afer both purchasing a pillow online. “I found it all a bit frustrating,” said Roberta. “It was hard to learn why you would choose down feathers, cotton, or foam. Te manufacturer websites felt like they were from the 1990s. Tere were some reviews available on Amazon and Bed Bath & Beyond, which helped. In my interpretation, about 65% of reviews talked about sleep quality, which seems like a good sign for our frst risk. A lot of the reviews had to do with personal preference for frm versus sof pillows. I think we can ofer both kinds eventually, but we likely need to choose one at the beginning and that could impact some of our assumptions around market size. ” “I started out by searching Google,” said Koshi. “Amazon and BB&B dominated the results, as we expected, but there were a few specialty providers like BestPillow that ranked high. BestPillow lets you navigate their website by sleep issue, such as snoring or neck pain, which I found interesting. While I see some makers pushing hypoallergenic oferings, I didn’t see anyone who could meet our claims of being environmentally friendly. I agree that all the manufacturer websites felt ancient. I think there’s an opportunity to be smart about search engine optimization and really stand out if we can get the messaging right. I guess our next step is to visit the retail 20 Talking to Humans stores.” Observing the Customer Roberta ended up going to a Bed Bath & Beyond while Koshi went to a local department store. She watched three diferent people come in and pick through several diferent pillows, puzzling over the packaging material. One of them asked a store employee for help, and two pulled out their mobile phones to look online. She then watched a woman go right to a particular shelf, grab a pillow and head back to the aisle. Roberta’s plan was to balance observation and interaction, so she decided to jump in. “Pardon me,” she said “I am trying to fgure out which pillow to purchase and noticed that you went right to that one. Might I ask why you chose that pillow?” “Oh, I replaced some ratty old pillows in my house a few weeks ago,” the woman said, “and I liked this one so much that I thought I would replace my whole set.” “Do you mind if I ask how you decided to buy that pillow in the frst place? My name is Roberta, by the way.” “Nice to meet you, Roberta. I’m Susan. Well, I guess I started by researching online and...” A day later, the founders met to compare notes. “Te BB&B had good foot trafc,” Roberta said, “and I was able to watch ffeen people, and speak to ten. Of the ten, one knew what she wanted going into the store, three were basing their purchase just on packaging and store price, and six did Google searches on their phones, right there in the store. Tey were looking up reviews and pricing. You mentioned search engine optimization earlier — I think it could be even stronger with a fabulous mobile experience.” She looked down at her notes. “I also found that seven out of ten were trying to choose a pillow specifcally for better sleep, although their sleep problems were diverse. Finally, when I asked The Story 21 them why they were buying a pillow, the folks over 40 seemed to be in replacement mode, while the folks under 40 seemed to be reacting to a life change. Two people were moving to a bigger house from an apartment. Another person was moving in with their girlfriend, and another said that she got a new job and could now aford nicer things.” “I went to the home goods section of a high-end department store,” said Koshi. “I saw eighteen people, and fve of them knew what they wanted already. Te rest spent time puzzling over the packaging and, like your group, going online with their mobile phone. I spoke to nine shoppers. I said that I was a scientist trying to invent a new pillow. People thought that was pretty cool. Two of them admitted that they were buying the highest price pillow because they assumed that it had to be the best. Two got the cheapest because it was the cheapest. Te others had specifc preferences for down, cotton or foam based on the frmness they were looking for in a pillow. Te frmness preference seemed to be tied to a belief that they would sleep more soundly. On price, I was relieved to see that the prices of the better pillows were in line with what we were hoping to charge.” Roberta pulled out a pad. “So we saw thirty-three people and spoke to nineteen. Our sample set is still small, but Samantha told us to look for patterns and not worry about statistical signifcance right now. If we break our observations into a few metrics, what have we learned?” • 24% of shoppers knew what they wanted when they walked in • 52% looked up information on their phone in the store • 45% of shoppers purchased a mid-priced or high-priced pillow • 68% of the people we spoke to indicated that better sleep was a major driver of their choice 22 Talking to Humans • 37% of the people we spoke to were reacting to a life change • 37% of the people we spoke to were in replacement mode “I think the use of mobile phones is something we need to pay attention to and work into our strategy,” Koshi said. “I guess for our next step, we should follow Samantha’s suggestions to target urban professionals.” Regrouping A week and many interviews later, the team sat down with Samantha. “How did things go?” she asked. “I went to a downtown cofee shop at peak hour,” Koshi said. “At frst, everyone was in such a hurry to get to work that I didn’t get much response, but then I made a little sign I held up outside that promised ‘cofee for science,’ which started to get laughs and a lot of curiosity. I ended up talking to about ffeen people who matched our target of young urban professionals. I got to talk to them for about fve to twenty minutes each. It was actually very enjoyable. “One clear pattern was that people right out of school tended to have no clue. Tey either had never bought a pillow themselves, or if they had, it had been the cheapest thing they could get. A few admitted that they were probably going to buy new bedding. I know it is speculation, but I asked them to guess how they might go about looking for a pillow, based on how they shop for other things. Te common responses were searching on Google or Amazon, or walking into a Bed Bath & Beyond. “Te few folks in their later twenties or thirties whom I spoke to had usually bought at least one pillow — some from Amazon and some from retailers. Te ones who liked a frm pillow avoided The Story 23 down feathers. Te ones who wanted to upgrade to fancier duvets and high thread-count sheets all seemed to go with duck and goose feathers. Tey didn’t know any brands and instead relied on product packaging. Amazon buyers did actually read the reviews. All these folks were only planning on buying new pillows when they were moving to a bigger apartment because they were getting married or something.” “Yes, that aligns with what we learned when we spoke to people in the retail stores and what I saw with my other interviews,” said Roberta. “Pillow buying seems to be tied to life events like moving and marriage and such. I interviewed a diferent group. A whole bunch of our old classmates responded to my email or my Facebook post. I even had some folks pass me on to their friends, and so I got to talk to some people who didn’t go to school with us. “Like you, I saw a lag efect afer someone graduated from college. When new graduates told me that they had not spent any money on their linens yet, I inquired further and found out that their initial spending money was predominately going towards clothes. I spoke to twelve people between 22 and 25, and roughly 60% had actually bought a pillow in the last few years. I saw similar trends as you, although most went right to Google, Amazon or a few specialty online retailers. It seemed like a very online crowd. Te price sensitive ones stayed away from down. Tey didn’t have much to go on for brand, but the reviews helped. Te women defnitely cared more about quality and put more efort into their hunt.” “Te good news is that everyone thought inventing a new pillow was an awesome idea!” said Koshi. Samantha chuckled. “Of everything I’ve heard you say, that last bit is probably the least useful. It’s easy to say something is cool. It’s another thing to actually buy. Te good news is, you are a lot more educated about your market than you were last time we met. 24 Talking to Humans I see from your notes that you have either spoken to or observed 72 people. We should be able to see some patterns from that. Let’s revisit our critical assumptions.” Challenging Assumptions Te team looked at their initial list. 1. We believe that people care about sleep quality when making a purchase decision. “68% of the retail shoppers indicated that this was a major factor,” said Roberta. “Of our young urban professionals, we were able to ask this of only a portion of our interviewees. Only 56% indicated that it was a factor, but if we factor out the new graduates, it was more like 70%. We’ve also read a lot of online reviews and have seen this come up repeatedly. We feel reasonably confdent that this is a common decision point in choosing a pillow,” said Koshi. “I’m glad you are approaching this with rigor and actually calculating metrics from your observations,” said Samantha. “Tat will prevent you from letting innate biases override your actual results. However, one word of advice. At this stage, don’t take any of your statistics too literally and don’t let any single number dominate your strategic thinking. Just as we’re not looking for statistical signifcance at this point, we also don’t want to start treating our results as if they are indisputable facts. How about the next assumption?” 2. We believe that we can sell online directly to customers. “We have seen some promising signs. 77% of our urban professionals start researching purchases with a search engine. Te question is whether they would discover, visit, or convert with our The Story 25 online store. We did see a ton of mobile usage in the retail stores and think there might be a chance to steal those customers if we have good enough search engine optimization. Overall, our conclusion is that we need more data here.” 3. We believe that our customers will be young urban professionals. “I need to run some numbers on size of market and the number of purchases we might expect from this group, but we still feel like this is a good group for us. We clearly saw purchase behavior. Tey want, and can aford, quality things, and prefer to buy things online.” 4. We believe that our very frst customers will be new graduates who need to outft their apartments. “Tis is where we were totally wrong. Buying behavior, or at least the willingness to buy something that isn’t the cheapest option, did not seem to be very prevalent among new grads. Only 25% of the newly minted grads we spoke with had purchased a pillow on their own. Instead, the evidence points us towards people in their mid-tolate twenties or early thirties. “We also saw a correlation between purchasing and life changes. While this was only 37% with our retail shoppers, it was 70% of our urban professionals. From an early adopter perspective, I wonder if we can do well targeting people who are getting married or moving to a larger apartment or house?” 5. We believe we can sell our pillows at a high enough price to cover our costs. “45% of our retail shoppers bought at least a mid-priced pillow. We admit that we visited reasonably high-end stores, but that was still a nice statistic to see. Te good news is that our initial target price is comparable with the high-end of the current market. We 26 Talking to Humans won’t be proftable at the beginning, but if we can scale and improve our manufacturing process then we can move into the black. Of course, they have to want to buy our pillow.” Samantha nodded. “To test that, you will need to actually try selling a few, which ties back to your second risk. But I’m glad you have spent time learning rather than rushing to sell. Overall, it sounds like you have gotten some solid intel. I’m also glad you caught the issue with college grads before you spent a lot of money and energy trying to target them. Have your eforts uncovered new risks or worries?” “I’m both excited and worried by how confused customers are,” Koshi said. “Every brand promises a better night’s sleep. I’m also worried about signals we picked up that the market might be divided into those who want a frm pillow versus a sof pillow. We think that’s erroneous thinking. Our pillow lands in the middle, and our studies show better results. I don’t know if people will believe our data. We really need to get the messaging right.” “As for me,” Roberta said, “I’m most worried about the size of our initial market, how quickly we could grow, and if we can survive to proftability.” “I’m not surprised,” said Samantha. “I have some suggestions. One of you should continue doing these interviews, but try adding a new spin. You are both worried about diferentiation and if people will understand or appreciate the proof from your scientifc studies. Let’s test some messaging. Given what you have said about mobile usage, maybe create an infographic that tries to make your case. Show it to people on a phone. Ask them to explain it to you. First you can see if they understand it, and then if they fnd it meaningful. “Expanding from qualitative research, I also think one of you should create a fnancial model that lets you play with how much The Story 27 you charge, how many items you might sell, and what your costs will be. Take into account what you have learned so far and see if your business model adds up. “Finally, I think you’ve learned enough to run some experiments around customer acquisition and sales. It is straightforward to create a basic online store using one of the hosted services. You can test selling a few pillows before you invest in manufacturing capability. Try driving trafc through Google or Facebook ads, and run some A/B tests around ad copy, landing-page messaging and price points. Study your metrics. Ten follow up with your customers and interview them on their buying process and decision.” Roberta’s eyes widened. “Wow. Maybe we can get our frst paying customer!” “Exactly,” said Samantha. “Just remember Steve Blank’s phrase about startups: you are in search of a scalable and repeatable business model. Run these experiments and keep in mind that your mission at this point is to learn before you scale. Don’t stop talking directly to customers. Your questions will likely evolve, but no matter what stage you are in, you’ll usually fnd that your best insights will come from talking to real people and observing real behavior.” 28 Talking to Humans Lessons Learned The Story 29 So what are the key takeaways from Roberta and Koshi’s adventure? 1. Customer discovery is about gaining much deeper insight into your customer, or your partners, or your market 2. Being told your idea is cool is not useful; seeing behavior that validates your customer’s willingness to buy is very useful 3. Prepare an interview guide before you get out of the building 4. To ask the right questions, you need to understand your risks and assumptions 5. Get creative when trying to recruit people — if at frst you don’t succeed, try something new 6. Sometimes observation is as powerful as interviews 7. Take good notes, especially on your key risks, so that you can calculate metrics later. Even better, set your target goals ahead of time! 8. Bring learning back and analyze your patterns as a team 9. Never stop asking hard questions about your business In the next section of this book, we’re going to dive into tactics and talk about all this and more in detail. How To PART TWO How To 31 Getting Started with Customer Discovery Qualitative research, i.e. talking to humans, is something you never want to stop doing, but it can defnitely feel intimidating at frst. Te good news is that if you go about it in a professional and thoughtful way, you will fnd lots of people who are willing to help and give you some of their valuable time. You need to begin with a core set of questions: t
Who do you want to learn from? t
What do you want to learn? t
How will you get to them? t
How can you ensure an efective session? t
How do you make sense of what you learn? 32 Talking to Humans Who Do You Want to Learn From? How To 33 If your desired customer is a doctor, it stands to reason that it won’t help you much talking to a plumber. If you were aiming for teenagers, would you talk to grandparents? Te frst step in trying to learn from the market is having an opinion about who your market actually is. I recommend thinking about a few categories: t
Te typical customer you envision if you get traction with your idea t
Your early adopter, i.e. the people who will take a chance on your product before anyone else t
Critical partners for distribution, fulfllment, or other parts of your business You might think you are creating a product for “everyone”, but that is not an actionable or useful description in the early stages. You need to get more specifc. Your job is to think through the kinds of people who have the problem you are interested in solving. Sometimes they have a particular job, or a state of mind, live in a particular part of the world, or belong to a certain age group. Standard demographics might be useful, or they might be irrelevant. What are the commonalities across your customer base? Here are some examples: • A hospital management system has to think about the hospital administrator who will buy their software and the actual hospital workers who would use it • An on-call veterinarian service needs to talk to pet owners • An online marketplace for plumbers might consider plumbers on the sell side, and home owners on the buy side 34 Talking to Humans You also want to think about your early adopters. Why do they matter? Most new products ft alongside a “technology adoption curve,” as illustrated below. New founders tend to obsess about their mainstream customer (represented in the chart as the early and late majority). However, by defnition, the mainstream is waiting for proof from early adopters before they try something. If you cannot get early adopters, you cannot move on. Early adopters are usually folks who feel a pain point acutely, or love to try new products and services. In our story of Koshi and Roberta, the scientists hypothesized that their early adopter would be urban professionals in their mid to late twenties. For the three customer examples we just gave, here are examples of early adopters: • Our hospital management system might target hospital chains still stuck with an archaic vendor • Our vet service might target busy 20-somethings in a major city • Our online market for plumbers might target solo practices on the sellside and frst-time home owners on the buy-side How To 35 Tere is no prescription for how narrowly or broadly you should cast your net for customer discovery interviews. However, the more focused you can be, the easier it is to make sense of your evidence. Special Note for B2B Products If you are selling to the enterprise, you should also think about the diferent kinds of participants in your sales process. In a classic enterprise sale, you will ofen have a strategic buyer (who is excited about the change you can bring), an economic buyer (who controls the purse), a technical buyer (who might have approval/blocker rights), and then the actual users of your product. Can you identify your champion? Can you identify who might be a saboteur? For B2B companies, Steve Blank also recommends that you start by talking to mid-level managers rather than the C-suite. It can be easier to get their time, it is ofen easier to get repeat conversations, and, most importantly, it will allow you to get better educated before you go up the chain. 36 Talking to Humans What Do You Want to Learn? How To 37 Go into every customer interview with a prepared list of questions. Tis list, which we refer to as an interview guide, will keep you organized. You will appear more professional, and it will ensure that you get to your most important questions early. How do you know your most important questions? I like to begin by understanding my most important, and most risky, assumptions. Tose tend to be the areas where you need to gather insights most urgently. You can uncover your assumptions in a myriad of ways. You can use Alex Osterwalder’s business model canvas or Ash Maurya’s lean canvas. Personally, I ask these questions (see the Appendix for a worksheet and tips): • My target customer will be? • The problem my customer wants to solve is? • My customer’s need can be solved with? • Why can’t my customer solve this today? • The measurable outcome my customer wants to achieve is? • My primary customer acquisition tactic will be? • My earliest adopter will be? • I will make money (revenue) by? • My primary competition will be? • I will beat my competitors primarily because of? • My biggest risk to fnancial viability is? • My biggest technical or engineering risk is? • What assumptions do we have that, if proven wrong, would cause this business to fail? (Tip: include market size in this list) You should be able to look at this list and spot the assumptions that are both highly important and fairly uncertain. Be honest. You want to focus on the most important issues. 38 Talking to Humans In the case of our pillow entrepreneurs, they chose six initial risks which drove their research approach and frst set of questions. To give another scenario, in the last chapter we shared the example of an on-call veterinarian service. Te founders might identify a set of risks: 1. Pet owners are frustrated having to go to a vet and would rather have someone come to them 2. Customers are willing to pay a big premium to have a vet show up at their door 3. We think busy urbanite pet owners will be our early adopters 4. We think people currently discover their vets either through word of mouth or online searches 5. We can affordably acquire our customers through targeted Google search ads 6. We can recruit enough vets across the country to make this a big enough business 7. With travel baked in, our vets can see enough people in a day to be fnancially viable Not every assumption can be tested efectively through qualitative research, but in this case, our founders can probably get some insights on risks 1, 3, 4, and 6 just by talking to people. Risks 1, 3 and 4 would be focused on pet owners, while #6 would be focused on vets. Get Stories, Not Speculation When you are contemplating your questions, be careful with speculation. Humans are spectacularly bad at predicting their future behavior. It is tempting to say, “Would you like this idea?” or “Would you buy this product?” Unfortunately, you really have to treat those How To 39 answers with a great deal of skepticism. It is more efective to ask your interview subject to share a story about the past. For example, when our fctional scientists Koshi and Roberta created their interview plan, the questions were focused on getting the interviewee to tell a story about their last pillow buying experience. Keeping with our second example of an on-call vet service, the team might have a loose interview plan that looks like the following: • Warm up: concise intro on the purpose of the conversation • Warm up: basic questions about person and pet (name, age, picture) • Who is your current vet? Can you tell me about how you found and chose him/her? • Please describe the last time you had to take your pet to the vet for a checkup • Walk me through the process of scheduling a time to visit the vet. • What was frustrating about that experience? • What did you like about that experience? • Have you ever had an emergency visit to a vet? if yes, can you describe that experience for me? • Have you ever thought about changing vets? why / why not? Ask Open-Ended Questions Your goal is to talk little and get the other person sharing openly. To that end, it is imperative that you structure open-ended questions, or at minimum follow up yes/no questions with an open-ended question that gets them talking. One tip is to try to ask questions that start with words like who, what, why and how. Avoid questions that start with is, are, would, and do you. But remember, if you do get a yes/no answer to a 40 Talking to Humans question, you can always follow up in a way that gets them talking. An interesting open-ended question, which Steve Blank likes to use to conclude his interviews, is: “What should I have asked you that I didn’t?” Testing for Price Two of the hardest questions to answer through qualitative research are: will people pay? and how much will they pay? Speculative answers on this topic are extremely suspect. You can learn a lot, however, by asking questions like: • How much do you currently spend to address this problem? • What budget do you have allocated to this, and who controls it? • How much would you pay to make this problem go away? (this can lead to interesting answers as long as you don’t take answers too literally) My recommendation is to set up a situation where the subject thinks they are actually buying something, even if they know the thing doesn’t exist yet. Kickstarter and other crowdfunding platforms are used by a lot of teams to test pre-order demand. For expensive corporate products, you can also try to get customers to buy in advance or sign a non-binding letter of intent to buy. Te key thing to remember is that people don’t honestly think about willingness to pay unless they feel like it is a real transaction. Getting Feedback on a Prototype Sometimes you will want to get reactions to a product solution. You can learn a lot by putting mockups or prototypes in front of people, but, as with all speculation, you should interpret reactions with a degree of skepticism. If you show your interview subject a proposed solution, you need to separate this step from your questions about their behavior. How To 41 Ask your questions about behavior and challenges frst, so that the discussion about product features does not poison or take over the conversation. People do love talking features! The Magic Wand Question Some people like to ask, “if you could wave a magic wand and have this product do whatever you want, what would it do?” Personally, I avoid questions like this because customers are too constrained by their current reality to design efective solutions. It is the customer’s job to explain their behavior, goals, and challenges. It is the product designer’s job to come up with the best solution. Tere is one variation to the magic wand question that I do like, however, because it focuses on problems and not solutions: “If you could wave a magic wand and solve any problem, what would you want to solve?” I suspect, however, that you will fnd many people struggle with such an open question. Design “Pass/Fail” Tests Customer discovery is made up of a lot of qualitative research, but it helps to take a quantitative mindset. Set goals for key questions and track results. For example, halfway through their initial research, our scientists Koshi and Roberta already knew stats like: • 24% of shoppers knew what they wanted when they walked in • 45% of shoppers purchased a mid-priced or high-priced pillow • 68% of the shoppers we spoke to indicated that better sleep was a major driver of their choice Even better would have been if they had set targets ahead of time. For example, they might have set the following goals: • Because we are a new brand, we are hoping that most shoppers are undecided. We want to see that 40% or fewer shoppers already know what 42 Talking to Humans they want when they walk in • Because our pillow is expensive, we want to see that at least 40% of the shoppers buy mid or high-end models • Because we believe that sleep quality is a major differentiator for our product, we want over 60% of shoppers to indicate that this is a major factor in their decision making process Te numerical target you choose can be an educated guess. You do not need to stress over picking the perfect number. It is more important that you set a goal and really track what is happening. Setting a target forces you carefully think through what you are hoping to see, and makes decisions and judgment calls a bit easier as you review your data. A Guide, Not a Script An interview guide is not a script. You do not need to read from it like an automaton. You should feel free to veer of of it if the conversation brings up something interesting and new. It will likely evolve as you learn from the market and unearth new questions. But always plan, prioritize and prep your questions before any session. Observation Can Be As Powerful As Questions Sometimes the best thing you can do is sit back and watch someone’s behavior. You might watch their purchase process, or examine how they go about solving a particular problem. As you think about what you want to learn, also think through how you might gather data through observation rather than direct interviews. In our story of Koshi and Roberta, the two got some of their most valuable insights by going to linen stores and watching potential customers struggle to buy a pillow. Tey observed behavior and only then jumped in to ask questions. Tis technique cannot always be used. For example, when my How To 43 team was trying to validate a weight loss product idea, it did not feel practical to watch people go about their diet. Instead we did interviews and then put a group of customers through a two-week concierge experiment (see Glossary) where we manually acted out the diet experience. But, where possible, observing uninfuenced behavior can lead to great insights. 44 Talking to Humans How Do You Find Your Interview Subjects? How To 45 Entrepreneurs new to customer development are ofen intimidated at the thought of approaching complete strangers. It might surprise you to hear that people are ofen very willing to help out. Tis is especially true if you are working on a topic that interests them and you approach them nicely and professionally. Tere are three general rules to keep in mind when recruiting candidates to speak with: 1. Try to get one degree of separation away (don’t interview your mom, your uncle, or your best friends) 2. Be creative (and don’t expect people to come to you) 3. Fish where the fsh are (and not where they are not) Get Creative One aspiring entrepreneur wanted to target mothers of young children. She had heard stories about talking to people in a cofee shop, but felt like it was too unfocused. So she tried hanging around school pickup zones, but the moms were too busy and refused to speak to her. Next, she tried the playground, where she fgured moms would be bored watching their kids play. Tis worked reasonably well, but she was only able to get a few minutes of anyone’s time. So instead, she started organizing evening events for moms at a local spa where she bought them pedicures and wine. Te time of day worked because the moms could leave the kids at home with their partner. Te attendees had a great time and were happy to talk while they were getting their nails done. Find the Moment of Pain If you can connect with people at the moment of their theoretical pain, it can be very illuminating. My colleague Alexa Roman was working with an automotive company and they had a concept tied 46 Talking to Humans to the experience of getting gas. So Alexa and team visited a series of gas stations. Tey watched consumers go through the process of buying gas. Ten they approached them and asked questions. By thinking about the moment of pain they wanted to address, they knew exactly where to fnd their consumers and they were able to gather valuable observational research. Make Referrals Happen Use referrals to your advantage. Let’s say you want to talk to doctors. Tey are busy and have strong gatekeepers. I bet you know how to get to at least one doctor, however. Tat doctor will know other doctors. Even if your doctor happens to be a close friend and thus breaks the “more than one degree of separation” guideline, she can still give you advice on when might be a good time to talk to a doctor. She can also connect you with other doctors. You should use referrals as much as possible. Set a goal of walking out of every interview with 2 or 3 new candidates. When you end an interview, ask the person if they know others who face the problem you are trying to solve. If they feel like you have respected their time, they will ofen be willing to introduce you to others. Conferences & Meetups Conferences and meetups can be an amazing recruiting ground, because they bring a group of people with shared interests into one place. You just need to be respectful of people’s time. I have found that it is extremely efective to ask people for their time, but for later, afer the conference or meetup. Get their business card, let them get back to networking, and then have an in-depth conversation when it fts their schedule. Immediately afer the conference while their memories are still fresh, send them a short email that reminds them where you met, and give your ask for a conversation. Tis How To 47 works as efectively for in-demand panel speakers as it does for other attendees. Meetups are usually inexpensive, but conference tickets can be pricey. If you are on a budget, you can “hack” expensive conferences by intercepting people outside of the building, or, if you can get access to the attendee or speaker lists ahead of time, contacting people directly and meeting them near the event. Meetup.com has decent search tools to discover relevant events in your area, and a few good Google search queries can usually get you to a short list of conferences that ft your needs. Enterprise Customers Finding interviewees can be harder when you are focused on an enterprise customer. You need laser-like targeting. In addition to conferences, LinkedIn can be extremely useful. If you have hypotheses on the titles of the people you are seeking, run searches on LinkedIn. You might be able to get to them through a referral over LinkedIn, or you might need to cold call them through their company’s main phone number. You then have to decide on your approach method. You can either ask for advice (where you make it clear that you are not selling anything), or you can go in as if you were selling something specifc. Advice vs Selling Asking for advice should be your default method early in your customer discovery process. You will have better luck gaining access. People like being asked (it makes them feel important). Steve Blank used to call people up and say something like, “My name is Steve and [dropped name] told me you were one of the smartest people in the industry and you had really valuable advice to ofer. I’m not trying to sell you anything, but was hoping to get 20 minutes of your time.” 48 Talking to Humans Another efective spin on “asking for advice” is to create a blog focused on your problem space, and ask people if you can interview them for an article. When do you approach someone as if you were selling a product? Tis method is useful if you are past initial learning and want to test your assumptions around customer acquisition and messaging. Just don’t jump into sales mode too early. Beneftting from Gatekeepers If LinkedIn isn’t helping you and you need to reach high up in an organization, another approach is to call the CEO’s ofce. Your goal is not to talk to the CEO but actually their executive assistant. His job is to be an efective gatekeeper, so if you explain, “I’m looking to talk to the person who handles X”, they will ofen connect you to the right person (especially if you are pleasant and professional — notice the trend on that one?). Te added advantage of this method is if you end up leaving a voice mail for your intended contact, you can say “Jim from [CEO’s name]’s ofce gave me your name”. Dropping the boss’ name tends to improve response rates. Another approach is to send a targeted email into an organization with a very short email that asks for an introduction to the right person to speak to. You can make guesses as to email addresses based on LinkedIn queries. For this tactic to work, you must keep your emails extremely concise. Students and Researchers While people are willing to grant time to polite people who ask for advice, you have an extra advantage if you are a student or academic researcher. In other words, if you are a student or researcher, say so. As an extra incentive, you might also ofer to share the results of your research with your interview subjects. How To 49 You Might Be Surprised Another colleague of mine, Jonathan Irwin, was working with a Fortune 50 company. Te client team wanted to interview a special kind of oil platform engineer, of which there were less than 20 in the world! To access these people required security clearance and safety training. We challenged the team to fnd a way, expecting that they would have to rely on video conferencing or phone calls. However, the team started researching this speciality profession through Google and discovered that there was an onshore training facility just an hour away. Te moral of the story is that it ofen isn’t as hard as you think. No Fish in the Sea When I say fsh where the fsh are, it is really important to remember the fip side to that statement: don’t fsh where the fsh are not. If a method isn’t working, try something new. We were doing a project with a major magazine testing out new product ideas. Our target was busy women, and we knew that the readership correlated closely with shoppers of Te Container Store (a retail store). So we parked out front of a store and intercepted folks as they came in and out. People were willing to speak for a few minutes, but many were in a bit too much of a rush. Ten one of our teammates discovered a sample sale happening around the corner. Tere were probably 200 bored women waiting in line, most of whom were happy to talk to us to pass the time. (Note: fnding bored people stuck in line is a common recruiting hack.) Still, we didn’t feel like we were targeting quite as narrowly as we wanted (busy, working women) or as geographically broadly (we didn’t want to just talk to New Yorkers). So we turned to the magazine’s social media presence. We created a short online survey to help us qualify responses, and the magazine posted a link to their Twitter and Facebook pages with a catchy sentence. We had hundreds of women fll out the survey, and then we picked our top 50 Talking to Humans thirty candidates and scheduled calls. Online Forms & Landing Pages In a similar vein, one efective tactic is to create an online form or landing page and build up a list of people to contact. Below is an example of a landing page. Our team was testing a product idea for better home organization. Tis landing page test actually consisted of a three-step funnel with a call to action, a price choice, and then a request for an email address. We tracked the conversion metrics carefully and used the emails to schedule interviews. Caveat: driving trafc is never a trivial process. If you have budget, Google or Facebook ads can work. Otherwise, you can try to generate some word of mouth on social media or through bloggers. How To 51 Conclusion Hopefully what you are picking up through these examples is that there is no single way to get to people. It takes some creativity and hustle, but it isn’t as hard as you might think. Trust me, people will not think you are rude if you carry yourself well and act professionally. Check Out the Appendix for Examples Te Appendix has more tips and examples for cold email and voice mail approaches. 52 Talking to Humans How to Ensure an Effective Session? How To 53 I recommend the following guidelines for running a productive interview session. Do Your Interviews In Person Te quality of your learning can vary a lot depending on your communication method. Talking in person is by far the best approach. You can read body language and build rapport much easier. Remember that a huge percentage of human communication is non-verbal, so why blind your senses if you don’t have to? Te next best approach is video conferencing, because at least you can still read someone’s facial expressions. Phone calls should be your method of last resort (sometimes there is no choice), and I would entirely avoid using text-based mediums like email or chat. Talk to One Person at a Time I believe in talking to one person at a time. It is useful to have a second person on your side quietly taking notes. I strongly recommend avoiding focus groups for two reasons: 1. you want to avoid group think; 2. you will really struggle to focus on one person’s stories, and drill into areas of interest, when you are juggling multiple people. Adding a Note Taker Bringing a note taker will allow you to stay in the moment without worrying about getting every bit down on paper. You can stay focused on the topics, the body language, and where to take the conversation. If you have to take your own notes, that’s not the end of the world. It can sometimes make for a more intimate conversation. Just remember to write up your notes right afer the session or you will lose a lot of detail and color that you weren’t able to write down. You can also ask the interview subject if you can record them, 54 Talking to Humans and many people are willing. Te risk is that a recorder can inhibit the conversation, but most people forget that they are being recorded once the discussion is fowing. I highly recommend that you play back the audio and write up your notes soon afer the session, both because writing up notes will reinforce what you learned in your own mind, and also because written notes are easier and faster for both you and your teammates to scan. I’ve found that once audio or video is more than a couple weeks old, somehow they never get touched again. Start With a Warm Up & Keep It Human When you kick things of, concisely explain why you are there, and thank them for the time. Launch into things with one or two easy warm up questions. For example, if you are talking to a consumer, you might ask where they are from and what they do for a living. If you are talking to enterprise, you might ask how long they have been with their company. You don’t want to spend a lot of time on this stuf, but it does get the ball rolling. Have a written or printed list of questions, but don’t rigidly read from your list. Be in the moment. Make the interview subject feel like you are really listening to them. Disarm Your Own Biases Human beings have an amazing ability to hear what they want to hear (this is called “confrmation bias”). Go into each session prepared to hear things that you might not want to hear. Some entrepreneurs even take the mindset that they are trying to kill their idea, rather than support it, just to set the bar high and prevent themselves from leading the witness. Get Them to Tell a Story As I mentioned in the chapter “What Do You Want to Learn,” How To 55 humans are terrible at predicting their own behavior. If you ask any speculative questions, be prepared to listen with a healthy dose of skepticism. I far prefer to get people telling stories about how they experienced a problem area in the past. In particular, try to fnd out if they have tried to solve the problem. What triggered their search for a solution? How did they look for a solution? What did they think the solution would do, before they tried it? How did that particular solution work out? And if they are struggling to remember specifcs, help them set the scene of their story: what part of the year or time of day? Were you with anyone? As they are telling their story, follow up with questions about their emotional state. You might get some historical revisionism, but what you hear can be very illuminating. Te researchers at Meetup.com, who borrow from Clayton Christensen’s Jobs To Be Done framework, use an interesting tactic to help their subjects get in story mode. When they are asking someone to take them through a purchase experience, from frst thought through purchase and then actual product usage, they say: “Imagine you are flming the documentary of your life. Pretend you are flming the scene, watching the actor playing you. At this moment, what is their emotion, what are they feeling?” Look for Solution Hacks One of the best indicators that the market needs a new or better solution is that some people are not just accepting their frustration with a particular problem, but they are actively trying to solve it. Maybe they have tried a few diferent solutions. Maybe they have tried hacking together their own solution. Tese stories are a great indicator of market need. Understanding Priority For someone to try a new product, their pain usually needs to be 56 Talking to Humans acute enough that they will change their behavior, take a risk, and even pay for it. If you feel like you are seeing good evidence that someone actually has a problem, it is worth asking where it ranks in their list of things to solve. Is it their #1 pain, or something too low in priority to warrant attention and budget? Listen, Don’t Talk Try to shut up as much as possible. Try to keep your questions short and unbiased (i.e. don’t embed the answer you want to hear into the question). Don’t rush to fll the “space” when the customer pauses, because they might be thinking or have more to say. Make sure you are learning, not selling! Or, at least make sure you are not in “sales” mode until the point when you actually do try to close a sale as part of an experiment. Follow Your Nose and Drill Down Anytime something tweaks your antenna, drill down with follow up questions. Don’t be afraid to ask for clarifcations and the “why” behind the “what.” You can even try drilling into multiple layers of “why” (run an Internet search for “Five Whys” for more info), as long as the interviewee doesn’t start getting annoyed. Parrot Back or Misrepresent to Confrm For important topics, try repeating back what the person said. You can occasionally get one of two interesting results. Tey might correct you because you’ve misinterpreted what they said. Or, by hearing their own thoughts, they’ll actually realize that their true opinion is slightly diferent, and they will give you a second, more sophisticated answer. Another approach is to purposefully misrepresent what they just said when you parrot it back, and then see if they correct you. But How To 57 use this technique sparingly, if at all. Do a Dry Run If you are a beginner at customer discovery, do a dry run with a friend or colleague. See how your questions feel coming out of your mouth. Get a sense of what it is like to listen carefully and occasionally improvise. Getting Feedback on Your Product If you want to get feedback on your product ideas, whether you show simple mockups or a more polished demo, there are a few important tips to keep in mind: As I mentioned before, separate the storytelling part of your session from the feedback part. People love to brainstorm on features and solutions, and this will end up infuencing the stories they might tell. So dig into their stories frst, and gather any feedback second. Second, disarm their politeness training. People are trained not to call your baby ugly. You need to make them feel safe to do this. Ask them up-front to be brutally honest, and explain that it is the very best way for them to help you. If they seem confused, explain that the worst thing that could happen is to build something people didn’t care about. Finally, keep in mind that it is incredibly easy for people to tell you that they like your product. Don’t trust this feedback. Instead, you need to put people through an actual experience and watch their behavior or try to get them to open their wallet. Tere is no right answer on how polished your early mockups need to be. If you are in the fashion space, you need to have a high degree of visual polish as table stakes. If you are creating a solution for engineers, you probably need much less. Just don’t wait for perfection, because initial product versions rarely get everything right. You need to spot your errors sooner rather than later. 58 Talking to Humans How Do You Make Sense of What You Learn? How To 59 Your goal is not to learn for learning’s sake. Your goal is to make better decisions that increase the odds of success. So how do you translate your observations into decisions? Te frst step is to make sense of your patterns. Take Good Notes To fnd your patterns, frst you need to track the data. Tis is easy if you bring a good notetaker to the interview, but otherwise, make sure that you write up your notes as soon afer your conversation as possible. Make them available to the entire team with Google Docs or the equivalent. At the start of every entry, note the following information: • Name of interview subject • Date and time • Name of interviewer • In person or video conference • Photo (if you have one) Ten at the start of your notes, include basic descriptive information of the interview subject. Quantitative Measures If you are setting specifc metric goals for your interviews, you might set up a shared spreadsheet that essentially acts as a running scorecard for how you are doing and how you are tracking to targets. EXAMPLE Let’s imagine that you have invented a new air purifer that triples the growth speed of greenhouse plants. Now you plan to talk to 20 60 Talking to Humans farmers, and you have a few core questions: • Will their business actually beneft from increased growth speed? You are assuming that increased volume will help rather than hurt. You plan to talk to growers of different crops with the goal of fnding crops where 60% or more of farmers want increased volume. • Are farmers spending any money today on growth accelerator solutions? Your qualitative research will drill into what and why, but your metrics goal says that you hope at least 50% of the market is already spending at least some money. • Do they have the facilities to support your purifer? In this case, you need your purifer to be both in a specifc location, but also have access to an electrical outlet. You are hoping that 70% of the farmers have an outlet 20 feet or closer to your spot. Here is the kind of spreadsheet that you and your team might track: As Samantha advised Koshi and Roberta in the fctional story, turning your observations into quantifable metrics is both useful and tricky. Our brains like to infuence our thinking with cognitive biases, especially fltering results for what we want to hear. Calculating actual metrics helps fght against that dynamic. How To 61 At the same time, you have to beware a diferent kind of bias: our desire to turn statistics into facts. Hopefully you are getting enough data points that you can trust the patterns, but do not confuse this with statistical signifcance or take your results too literally. My advice is to calculate metrics, but remain skeptical of them, don’t obsess over any one particular metric, and continue to question what is behind your numbers. Dump and Sort Exercise Bring your team together and arm them with sticky notes and sharpies. Give everyone 10 minutes to jot down as many patterns and observations as they saw during their interviews. Put all the sticky notes on a wall and have someone sort them into groups. As a team, discuss the patterns, and then re-review your assumptions or business canvas and see what might need to change or require greater investigation. Look for Patterns and Apply Judgement Customer development interviews will not give you statistically signifcant data, but they will give you insights based on patterns. Tey can be very tricky to interpret, because what people say is not always what they do. You don’t want to react too strongly to any single person’s comments. You don’t want to take things too literally. But neither do you want to be bogged down trying to talk to thousands of people before you can make a decision. You need to use your judgement to read between the lines, to read body language, to try to understand context and agendas, and to flter out biases based on the types of people in your pool of interviewees. But it is exactly the ability to use human judgement based on human connections that make interviews so much more useful than surveys. Ultimately, you are better of moving fast and making decisions 62 Talking to Humans from credible patterns than dithering about in analysis paralysis. Don’t Abdicate Your Role As Product Designer It is not the job of the customer to design your product. It is yours. As you are gathering information and making decisions, act like a intelligent flter, not an order-taker. Expect False Positives While all entrepreneurs get their fair share of naysayers and skeptics, you have to be wary of the opposite problem in customer development interviews. People will want to be helpful and nice, and your brain will want to hear nice things. As you are weighing what you have learned, just keep this in mind. The Truth Curve I am a big believer in qualitative research. I think a good product team should build a regular cadence of talking to relevant people into their process. However, you don’t want your only source of learning to be talking to people. You don’t really know the absolute truth about your product until it is live and people are truly using it and you are making real money from it. But that does not mean you should jump straight to a live product, because that is a very expensive and slow way to iterate your new business. Get into the market early and begin testing your assumptions right away, starting with conversations and proceeding from there. It will dramatically increase the odds that you will create a product that customers actually want. As you build confdence, test with increasing levels of fdelity. I think of it like peeling an onion in reverse. I created the accompanying chart to demonstrate the levels of believability for diferent kinds of experiments. How To 63 Talking to people is powerful. It tends to give you your biggest leaps of insight, but, as I keep on repeating, what people say is not what they do. You might show people mockups and that might give you another level of learning and feedback, but reactions still need to be taken with skepticism. Concierge and “Wizard of Oz” experiments, where you fake the product through manual labor (see Glossary) will give you stronger evidence, because you put people through an experience and watch their actions. Te next layers of the onion are to test with a truly functional “Minimum Viable Product” (see Glossary) and beyond. Te point I want to make is that all of the steps on the curve can be very useful to help you learn, make smarter decisions, and reduce risk, but you need to use your head, and apply judgement to everything you are learning. 64 Talking to Humans How many people to talk to? Tere is no pat answer to this question. A consumer business should talk to an order of magnitude more people than a business that sells to enterprise. If you are in the consumer space and haven’t spoken to at least 50 to 100 people, you probably have not done enough research. In his I-Corps course, Steve Blank requires his teams, many of which are B2B, to talk to at least 100 people over 7 weeks. I advise that you never stop talking to potential customers, but you will probably evolve what you seek to learn. If you see the same patterns over and over again, you might change things up and examine diferent assumptions and risks. For example, if you feel like you have a frm understanding of your customer’s true need, you might move on to exploring how they learn about and purchase solutions in your product category today. And don’t forget that observing your customers can be as powerful as directly talking to them. Lead with Vision Customer Development and lean startup techniques are some of the most powerful ways to increase your odds of success, but they are not a replacement for vision. You need to start with vision. You need to start with how you want to improve the world and add value to people’s lives. Te techniques we’ve discussed in this book are among a body of techniques that let you reality check your vision, and optimize the path you will take to achieve your vision. How To 65 Conclusion Toughtful qualitative research is a critical tool for any entrepreneur. Hopefully this book has given you some new strategies for how to put it to work for your needs. Creating a new business is tremendously challenging. Te ways you can fail are numerous. t
You have to get the customer and market right t
You have to get the revenue model right t
You have to get the cost structure right t
You have to get customer acquisition right t
You have to get the product right t
You have to get the team right t
You have to get your timing right Screw up any one of those and you are toast. Tere is a reason why entrepreneurship is not for the faint of heart. But we’re not here to be faint of heart. We are here to change the world. Dream big. Be passionate. Just be ruthless with your ideas and assumptions. Customer discovery and lean experimentation can truly help you chart a better path and fnd success faster and with more capital efciency. Don’t forget that as your business grows and changes, so too will your customer base. Keep on reality-checking your hypotheses. Keep on talking to humans. Appendix PART THREE Appendix 67 Cold Approach Examples When you are trying to reach someone you do not know, there are a few things to remember: 1. Keep things concise 2. Keep things convenient (meet near their ofce, etc) 3. Name drop when you can 4. Follow up if you don’t hear an answer, but don’t be annoying 5. If you are leaving a voice mail, practice it frst (you might think it sounds practiced, but to others, it will sound more professional) Example Email 1 To: [email protected] From: [email protected] John, I received your name from James Smith. He said that you had a lot of expertise in an area I am researching and recommended that we speak. I’m trying to study how companies are handling their expense report management workfows and the frustrations they are experiencing. I would be happy to share my research conclusions with you. Would you have 30 minutes to spare next week when I could buy you a cup of coffee and ask you a few questions? Many thanks for your time and I look forward to hearing from you, Jane Doe 68 Talking to Humans Example Email 2 To: [email protected] From: [email protected] John, I have been working on some new solutions in the area of expense report management, and I was told that you have a lot of expertise in this area. We started this journey because of personal frustration, and we’re trying to fgure out how to make expense reporting much less painful. Would you have 30 minutes to give us some advice, and share some of your experiences in this domain? I assure you that I’m not selling anything. I would be happy to come by your offce or arrange a quick video conference, at your preference. Many thanks, Jane Doe Example Voice Mail Message “Hello, my name is Jane Doe. I was referred to you by James Smith, who said I would beneft from your advice. I am currently researching how companies are handling their expense management workfows. I understand you have a lot of expertise in this area. I was hoping to take just 30 minutes of your time to ask you a few questions. I’m not selling anything and I would be happy to share my research conclusions with you. You can reach me at 555-555-5555. Again, this is Jane Doe, at 555-555-5555, and thank you for your time.” Final Note Cold calling is never anyone’s favorite thing to do, but it isn’t nearly as painful as you imagine. You have nothing to lose and everything to gain. So give yourself a determined smile in the mirror, and go get them! Appendix 69 Business Assumptions Exercise I am agnostic about the framework you choose to use to map out your business assumptions. Alexander Osterwalder’s business model canvas and Ash Maurya’s lean canvas are both powerful tools. I also ofen fnd myself using this simple set of questions to lay out a belief system around an idea: Try to make your assumptions as concise and specifc as possible. You want to be able to run an experiment against it to see if it is true. My target customer will be? (Tip: how would you describe your primary target customer) The problem my customer wants to solve is? (Tip: what does your customer struggle with or what need do they want to fulfll) My customer’s need can be solved with? (Tip: give a very concise description / elevator pitch of your product) Why can’t my customer solve this today? (Tip: what are the obstacles that have prevented my customer from solving this already) The measurable outcome my customer wants to achieve is? (Tip: what measurable change in your your customer’s life makes them love your product) 70 Talking to Humans My primary customer acquisition tactic will be? (Tip: you will likely have multiple marketing channels, but there is often one method, at most two, that dominates your customer acquisition — what is your current guess) My earliest adopter will be? (Tip: remember that you can’t get to the mainstream customer without getting early adopters frst) I will make money (revenue) by? (Tip: don’t list all the ideas for making money, but pick your primary one) My primary competition will be? (Tip: think about both direct and indirect competition) I will beat my competitors primarily because of? (Tip: what truly differentiates you from the competition?) My biggest risk to fnancial viability is? (Tip: what could prevent you from getting to breakeven? is there something baked into your revenue or cost model that you can de-risk?) My biggest technical or engineering risk is? (Tip: is there a major technical challenge that might hinder building your product?) And then answer the following open-ended question. Be creative and really examine your points of failure. Appendix 71 What assumptions do we have that, if proven wrong, would cause this business to fail? 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Afer you have looked at your business holistically and also answered the broad fnal question, mark the assumptions that would have a large impact on your business and feel highly uncertain. Now you know your priorities for customer discovery and the experiments you need to run! 72 Talking to Humans Teaching Exercise #1: Mock Interviews If you are using this book to try to teach customer discovery/ development, there is nothing like real-world practice to make learning stick. Before you send your class out into the world to conduct their own interviews, however, you might try a compact exercise like the following: Tools All participants should have pen and paper Preface: Choose a Topic Everyone in the class will interview each other based on the same topic, which means it needs to be something most people can relate two. Tere are two angles you might take: 1. Something that helps the interviewer dig up past behavior. For example, “Tell me about the last thing you purchased over $100.” Have the interview subject explain what they bought, what the purchase process was like from desire to actual ownership, how they made their purchase decision, etc. 2. Something that helps the interviewer unlock deeper motivations and desires. For example, “Tell me about your dream car.” Prompt your students not just to get people to describe the car, but to dig into the reasons behind the choice; they can also prompt for whether the interview subject has ever experienced driving the car. Appendix 73 Exercise Step 1: Intro, 5 minutes Explain the exercise, the topic that the students will use, and give a few specifc suggestions for questions they might ask. Example questions for the dream car: when did you fall in love with the car and why? of the reasons you shared, why are these the most important to you? how have you imagined using the car? etc Step 2: Interview Plan, 2 minutes Give your class the topic and let them spend 5 minutes on their own. Tey should write down no more than 6 questions to ask. Step 3: Pair Interviews, 5 - 7 minutes each Pair up your students. One will begin as the interviewer, and their opposite will be interviewed. Give them 7 minutes, and then switch the roles, keeping the pairs unchanged. Te new interviewer gets 7 minutes. Te person doing the interviewing should also take notes, which will give them some exposure to doing an interview solo as opposed to bringing a note-taker to help (which is what most people prefer to do when possible). Step 4: Observations and Questions, 5-10 minutes Ask the room to share observations, challenges, lessons or questions on what it was like to do a live interview. 74 Talking to Humans Teaching Exercise #2: Mock Approach Dean Chang, the Associate VP of Entrepreneurship at the University of Maryland, recommends a class exercise where one or more teams of students takes on the role of cold calling an “expert.” Te team has to do it over and over until they get it right. For this exercise, select one team and have them come to the front of the classroom. Teir job is to “cold call” a selected member of the teaching team. Te teacher will pretend to be an expert in the team’s target feld. Te team needs to get the expert to take the call, and smoothly transition into asking questions. Te job of the person playing the “expert” is to block the team’s misguided attempts to engage. When the team does something wrong, the expert declines the interview request, or ends the conversation, or gives them a gong. Ten the team has to start over again. Classic mistakes that should trigger the team starting over include long or unclear introductions, pitching the product/technology too soon, implying that the expert has problems and desperately needs help, and/or generally making the expert feel uncomfortable with the line of questioning. As Dean describes it, “We let the other teams ofer critiques and suggest plans of attack for winning over the expert and then the chosen team tries it again. Eventually afer being gonged several times in a row, they stop making the same mistakes and start to Appendix 75 converge on a good elevator pitch that praises and disarms the expert and paves the way to entering into an interview. Ten we stop the exercise.” Te exercise will probably be humorous and painful at the same time, but there is nothing like stumbling, or watching a team stumble, to realize why best practices are best practices. 76 Talking to Humans Screwing Up Customer Discovery So how do people screw up customer discovery? Here are a few antipatterns: 1. You treat speculation as confrmation Here are some question types that I don’t like — and if you ask them, you should heavily discount the answer: “would you use this?” “would you pay for this?” “would you like this?” I can’t say that I never ask these questions, but I always prefer behavioral questions over speculation. As contrast, here is a behavior-focused interaction: “Tell me about a time when you bought airline tickets online.” “What did you enjoy about the process? What frustrated you about the process?” “What diferent systems or methods have you tried in the past to book tickets?” 2. You lead the witness Leading the witness is putting the answer in the interviewee’s mouth in the way you ask the question. For example: “We don’t think most people really want to book tickets online, but what do you think?” Examine both how you phrase your questions and your tone of voice. Are you steering the answer? Ask open-ended, neutral questions before you drill down: “what was that experience of buying online tickets like?” 3. You just can’t stop talking Some entrepreneurs can’t help themselves — they are overfowing with excitement and just have to pitch pitch pitch. Tere is nothing Appendix 77 wrong with trying to pre-sell your product — that is an interesting experiment unto itself — but you should not mix this in with behavioral learning. If you do try to pre-sell, don’t just ask, “Would you pay for this?” but rather ask them to actually pay, and see what happens. Some people ask the question, “How much would you pay for this?” but I do not. Instead, try actually selling at diferent price points (albeit one at a time). I much prefer having the potential customer experience something, rather than speculate over something. 4. You only hear what you want to hear I see some people go into interviews with strong beliefs about what they like and dislike. When you debrief afer their custdev conversation, it is magical how everything they heard aligns perfectly with their opinions. Our brains are amazing flters. Leave your agenda at the door before starting a conversation. One way to solve this is to have two people for each interview — one person to ask questions, and the other to take notes. 5. You treat a single conversation as ultimate truth You’ve just spoken to a potential customer and they have really strong opinions. One instinct is to jump to conclusions and rush to make changes. Instead, you need to be patient. Tere is no defnitive answer for how many similar answers equals the truth. Look for patterns and use your judgement. A clear, consistent pattern at even 5 or 10 people is a signal. 6. Fear of rejection wins out Tis is one of the biggest blockers to people doing qualitative research, in my experience, because of fear of a stranger rejecting your advance or rejecting your idea. Many excuses, such as “I don’t know how to fnd people to talk to,” are rooted in this fear. JFDI. Customer development isn’t just about street intercepts. You can 78 Talking to Humans recruit people on Craigslist, Facebook and LinkedIn groups, and good old fashioned networking. 7. You talk to anyone with a pulse I see some teams taking a shotgun approach. Instead, defne your assumptions around who your customer will be and who your early adopter will be. You might even do a lightweight persona (see the book Lean UX for examples). Zoom in on those people and try to validate or invalidate your assumptions about your customers. It is ok to occasionally go outside your target zone for learning, but don’t boil the ocean. Focus, learn, and pivot if necessary. 8. You wing the conversation If you go into a conversation unprepared, it will be evident. Write up your questions ahead of time and force-rank them based on the risks and assumptions you are worried about. To defne your assumptions, you can answer the questions in the business assumptions exercise (previous section), or do a business model canvas or a lean canvas. Your exact method doesn’t matter as much as the act of prioritizing your risk areas. During your actual interview, do not literally read your questions from a piece of paper, but rather keep things conversational (remember, you are getting the subject to tell you stories). If you uncover something interesting, follow your nose and don’t be afraid to diverge from your initial priorities. 9. You try to learn everything in one sitting Rather than trying to go as broad as possible in every conversation, you are actually better of zooming in on a few areas which are critical to your business. If you have a huge range of questions, do more interviews and split the questions. Appendix 79 10. Only the designer does qualitative research It is ok to divide and conquer most of the time, but everyone on the team should be forced to get out and talk to real people. Note: you will probably have to coach newcomers on #5’s point about not jumping to conclusions. 11. You did customer development your frst week, but haven’t felt a need to do it since It is always sad to see product teams start things of with customer development, and then completely stop once they get going. It is perfectly fne to let customer discovery work ebb and fow. If your learning curve fattens, it can make sense to press pause or change up your approach. However, you want to build a regular qualitative cadence into your product process. It will provide a necessary complement to your quantitative metrics, because it will help you understand the reasons why things are happening. 12. You ask the customer to design your product for you Tere’s a famous line attributed to Henry Ford, “If I had asked people what they wanted, they would have said faster horses.” Remember, it is not the customer’s job to design the solution. It is your job. It is the customer’s job to tell you if your solution sucks. Get feedback, yes. Remember that the further away you are from a working product, the more you have to flter what you hear through your judgement and vision. Disclaimer As with all tips on lean and agile, there are always places and times to break the rules and do what is right for your context, and your business. 80 Talking to Humans Glossary Concierge and “Wizard of Oz” Experiments A concierge experiment is where you manually act out your product. An example in Eric Ries’ book Te Lean Startup shows an entrepreneur serving as a personal shopper for people before trying to design an automated solution. When my colleagues were testing a diet plan service, we did not want to rush to sofware before testing our assumptions. Instead, we interviewed participants about their food preferences, manually created meal plans which were emailed to them over two weeks, and interviewed them at various points in the process. At the end of the two weeks, we asked them to pay a set amount to continue, and tracked the conversion rate. A “Wizard of Oz” experiment is similar, with the diference being that the manual work is hidden from the customer. For example, another set of colleagues tested an idea for a smart task management system for married couples. Te twenty couples participating in the test thought that they were interacting with a computer system, but in reality they were emailing in to our team, who then processed the emails accordingly. We just said that the servers would be “down” at night! Minimum Viable Product (MVP) An MVP is the smallest thing you can create that gives you meaningful learning about your product. MVP is ofen used interchangeably with “experiment” in the broader community. I personally tend to reserve it specifcally for tests around the product, and not for experiments related to other business assumptions. It is best to think about MVPs as an ongoing process, rather than a single release. Validation is rarely that neat and tidy. Appendix 81 Scientifc Method I think the best way to explain the scientifc method is to quote the theoretical physicist, Richard Feynman: “In general we look for a new law by the following process: frst we guess it. Don’t laugh -- that’s really true. Ten we compute the consequences of the guess to see what, if this law is right, what it would imply. Ten we compare those computation results to nature, i.e. experiment and experience. We compare it directly to observation to see if it works. “If it disagrees with experiment, it’s wrong. Tat simple statement is the key to science. It doesn’t make a diference how beautiful your guess is, it doesn’t make a diference how smart you are, who made the guess or what his name is -- if it disagrees with experiment, it’s wrong. Tat’s all there is to it.” (Cornell lecture, 1964) It is relatively straightforward to apply the scientifc method to business. You accept that your ideas are hypotheses. You make them as specifc as possible so that you can guess the results, i.e. the implications, of your hypotheses. You design and run an experiment. If your hypothesized results do not match the results of your experiment, your hypothesis is proven wrong. However, business is about people, and people are highly complex and inconsistent compared to laws of nature. So if your experiment fails, you will still need to apply judgement about whether the errors are in the hypothesis or in the experiment. 82 Talking to Humans Other Learning Resources Authors Te two seminal books on the topics of lean innovation and customer development are Steve Blank and Bob Dorf ’s Te Startup Owner’s Manual and Eric Ries’ Te Lean Startup. Tere are a ton of other resources out there, from books to videos and blog posts. Rather than link to particular items and thus miss out on newer developments, here are a few names that I recommend you pay attention to: Alex Osterwalder, Alistair Croll, Ash Maurya, Ben Yoskowitz, Brant Cooper, Cindy Alvarez, David Bland, Jef Gothelf, Joel Gascoigne, Josh Seiden, Kevin Dewalt, Laura Klein, Patrick Vlaskovits, Rob Fitzpatrick, Salim Virani, and Tristan Kromer. Talking to Humans Website On our website talkingtohumans.com, you can get worksheet pdfs and sign up for our email list, where we send occasional notes based on useful resources we discover. Behind the Book 83 Gif Constable (gifconstable.com) is a repeat entrepreneur and currently the CEO of Neo, a global product innovation consulting company. He has held product design and business roles in six startups, and provided M&A and IPO services to technology frms while at Broadview/Jeferies. He was one of the earliest adopters & bloggers of the Lean Startup movement, co-organizes the 4,700-person Lean Lessons Learned meetup in New York, and tries to give back to the entrepreneurial community through mentoring and speaking engagements. He lives outside of New York City with his wife, two children, and an excessively rambunctious retriever. Giff Constable Talking to Humans was written by Gif Constable, at the instigation and with the collaboration of Frank Rimalovski of NYU’s Entrepreneurial Institute, and with the wonderful illustrations of Tom Fishburne. Behind the Book 84 Guide to Customer Discovery Frank Rimalovski brings over 20 years of experience in technology commercialization, startups and early-stage venture capital investing. He is executive director of the NYU Entrepreneurial Institute, managing director of the NYU Innovation Venture Fund, Adjunct Faculty at NYU’s Polytechnic School of Engineering, and an Instructor in the NSF’s I-Corps program, having trained and mentored hundreds of entrepreneurs in customer development and lean startup methodologies. Previously, he was a founding partner of New Venture Partners, director/entrepreneur-in-residence at Lucent’s New Ventures Group, and has held various positions in product management, marketing and business development at Sun Microsystems, Apple and NeXT. He lives outside of New York City with his wife, two daughters and his increasingly mellow mutt. Frank Rimalovski Tom Fishburne (marketoonist.com) started drawing cartoons on the backs of Harvard Business School cases. His cartoons have grown by word of mouth to reach 100,000 business readers a week and have been featured by the Wall Street Journal, Fast Company, and the New York Times. Tom is the Founder and CEO of Marketoon Studios, a content marketing studio that helps businesses such as Google, Kronos, and Rocketfuel reach their audiences with cartoons. Tom draws from 19 years in the marketing and innovation trenches at Method Products, Nestle, and General Mills. He lives near San Francisco with his wife and two daughters. Tom Fishburne Behind the Book 85 Like The Book? When Frank approached me to write this book, we both had the same goal of giving back to the community. We debated charging for the book, and pondered whether the question of free versus paid would afect how it was perceived. But ultimately, we decided to put it out into the world for free. Should you like Talking to Humans, and feel a need to contribute back to something, we would encourage you to think about doing one or all of the following: 1. Pay it back (and forward!) by mentoring another student or entrepreneur 2. Donate to one of our favorite causes: Charity: Water, Girls Who Code, Kiva or the NYU Entrepreneurial Institute 3. Share a link to the talkingtohumans.com website or give someone a copy of the book If this book has helped you in some small way, then that is reward enough for us. It’s why we did it. Gif Constable and Frank Rimalovski September 2014 talkingtohumans.com page intentionally blank Acclaim for Talking to Humans “Talking to Humans is the perfect complement to the existing body of work on customer development. If you are teaching entrepreneurship or running a startup accelerator, you need to make it required reading for your students and teams. I have.” Steve Blank, entrepreneur and author of The Startup Owner’s Manual “Getting started on your Customer Discovery journey is the most important step to becoming a successful entrepreneur and reading Talking To Humans is the smartest frst step to fnding and solving real problems for paying customers.” Andre Marquis, Executive Director, Lester Center for Entrepreneurship, University of California Berkeley “If entrepreneurship 101 is talking to customers, this is the syllabus. Talking to Humans is a thoughtful guide to the customer informed product development that lies at the foundation of successful start-ups.” Phin Barnes, Partner, First Round Capital “A lot of entrepreneurs pay lip service to talking to customers but you have to know how. Talking to Humans ofers concrete examples on how to how to recruit candidates, how to conduct interviews, and how to prioritize learning from customers more through listening versus talking.” Ash Maurya, Founder of Spark59 and author of Running Lean “When getting ‘out of the building,’ too many people crash and burn right out of the gate and wonder what happened. Talking to Humans is a quick and efective guide for how Lean Startup interviews should be done.” Dean Chang, Associate VP for Innovation & Entrepreneurship, University of Maryland #talkingtohumans talkingtohumans.com

Refer only to the context document in your answer. Do not employ any outside information. Use complete sentences.

Summarize the possible uses, that are addressed in the provided document, of Google Gemini.

**What is Google Gemini (formerly Bard)?** Google Gemini -- formerly called Bard -- is an artificial intelligence (AI) chatbot tool designed by Google to simulate human conversations using natural language processing (NLP) and machine learning. In addition to supplementing Google Search, Gemini can be integrated into websites, messaging platforms or applications to provide realistic, natural language responses to user questions. List of tasks Google Gemini can perform. Google Gemini can be applied pragmatically to complete various tasks. Google Gemini is a family of multimodal AI large language models (LLMs) that have capabilities in language, audio, code and video understanding. Gemini 1.0 was announced on Dec. 6, 2023, and built by Alphabet's Google DeepMind business unit, which is focused on advanced AI research and development. Google co-founder Sergey Brin is credited with helping to develop the Gemini LLMs, alongside other Google staff. At its release, Gemini was the most advanced set of LLMs at Google, powering Bard before Bard's renaming and superseding the company's Pathways Language Model (Palm 2). As was the case with Palm 2, Gemini was integrated into multiple Google technologies to provide generative AI capabilities. Gemini integrates NLP capabilities, which provide the ability to understand and process language. Gemini is also used to comprehend input queries as well as data. It's able to understand and recognize images, enabling it to parse complex visuals, such as charts and figures, without the need for external optical character recognition (OCR). It also has broad multilingual capabilities for translation tasks and functionality across different languages. How does Google Gemini work? Google Gemini works by first being trained on a massive corpus of data. After training, the model uses several neural network techniques to be able to understand content, answer questions, generate text and produce outputs. Specifically, the Gemini LLMs use a transformer model-based neural network architecture. The Gemini architecture has been enhanced to process lengthy contextual sequences across different data types, including text, audio and video. Google DeepMind makes use of efficient attention mechanisms in the transformer decoder to help the models process long contexts, spanning different modalities. Gemini models have been trained on diverse multimodal and multilingual data sets of text, images, audio and video with Google DeepMind using advanced data filtering to optimize training. As different Gemini models are deployed in support of specific Google services, there's a process of targeted fine-tuning that can be used to further optimize a model for a use case. During both the training and inference phases, Gemini benefits from the use of Google's latest tensor processing unit chips, TPU v5, which are optimized custom AI accelerators designed to efficiently train and deploy large models. A key challenge for LLMs is the risk of bias and potentially toxic content. According to Google, Gemini underwent extensive safety testing and mitigation around risks such as bias and toxicity to help provide a degree of LLM safety. To help further ensure Gemini works as it should, the models were tested against academic benchmarks spanning language, image, audio, video and code domains. Google has assured the public it adheres to a list of AI principles. At launch on Dec. 6, 2023, Gemini was announced to be made up of a series of different model sizes, each designed for a specific set of use cases and deployment environments. The Ultra model is the top end and is designed for highly complex tasks. The Pro model is designed for performance and deployment at scale. As of Dec. 13, 2023, Google enabled access to Gemini Pro in Google Cloud Vertex AI and Google AI Studio. For code, a version of Gemini Pro is being used to power the Google AlphaCode 2 generative AI coding technology. The Nano model is targeted at on-device use cases. There are two different versions of Gemini Nano: Nano-1 is a 1.8 billion-parameter model, while Nano-2 is a 3.25 billion-parameter model. Among the places where Nano is being embedded is the Google Pixel 8 Pro smartphone. When was Google Bard first released? Google initially announced Bard, its AI-powered chatbot, on Feb. 6, 2023, with a vague release date. It opened access to Bard on March 21, 2023, inviting users to join a waitlist. On May 10, 2023, Google removed the waitlist and made Bard available in more than 180 countries and territories. Almost precisely a year after its initial announcement, Bard was renamed Gemini. Many believed that Google felt the pressure of ChatGPT's success and positive press, leading the company to rush Bard out before it was ready. For example, during a live demo by Google and Alphabet CEO Sundar Pichai, it responded to a query with a wrong answer. In the demo, a user asked Bard the question: "What new discoveries from the James Webb Space Telescope can I tell my 9-year-old about?" In Bard's response, it mentioned that the telescope "took the very first pictures of a planet outside of our own solar system." Astronomers quickly took to social media to point out that the first image of an exoplanet was taken by an earthbound observatory in 2004, making Bard's answer incorrect. The next day, Google lost $100 billion in market value -- a decline attributed to the embarrassing mistake. Why did Google rename Bard to Gemini and when did it happen? Bard was renamed Gemini on Feb. 8, 2024. Gemini was already the LLM powering Bard. Rebranding the platform as Gemini some believe might have been done to draw attention away from the Bard moniker and the criticism the chatbot faced when it was first released. It also simplified Google's AI effort and focused on the success of the Gemini LLM. The name change also made sense from a marketing perspective, as Google aims to expand its AI services. It's a way for Google to increase awareness of its advanced LLM offering as AI democratization and advancements show no signs of slowing. Who can use Google Gemini? Gemini is widely available around the world. Gemini Pro is available in more than 230 countries and territories, while Gemini Advanced is available in more than 150 countries at the time of this writing. However, there are age limits in place to comply with laws and regulations that exist to govern AI. Users must be at least 18 years old and have a personal Google account. However, age restrictions vary for the Gemini web app. Users in Europe must be 18 or older. In other countries where the platform is available, the minimum age is 13 unless otherwise specified by local laws. Also, users younger than 18 can only use the Gemini web app in English. Is Gemini free to use? When Bard became available, Google gave no indication that it would charge for use. Google has no history of charging customers for services, excluding enterprise-level usage of Google Cloud. The assumption was that the chatbot would be integrated into Google's basic search engine, and therefore be free to use. After rebranding Bard to Gemini on Feb. 8, 2024, Google introduced a paid tier in addition to the free web application. Pro and Nano currently are free to use via registration. However, users can only get access to Ultra through the Gemini Advanced option for $20 per month. Users sign up for Gemini Advanced through a Google One AI Premium subscription, which also includes Google Workspace features and 2 terabytes of storage. What can you use Gemini for? Use cases and applications The Google Gemini models are used in many different ways, including text, image, audio and video understanding. The multimodal nature of Gemini also enables these different types of input to be combined for generating output. Use cases Businesses can use Gemini to perform various tasks that include the following: Text summarization. Gemini models can summarize content from different types of data. Text generation. Gemini can generate text based on user prompts. That text can also be driven by a Q&A-type chatbot interface. Text translation. The Gemini models have broad multilingual capabilities, enabling translation and understanding of more than 100 languages. Image understanding. Gemini can parse complex visuals, such as charts, figures and diagrams, without external OCR tools. It can be used for image captioning and visual Q&A capabilities. Audio processing. Gemini has support for speech recognition across more than 100 languages and audio translation tasks. Video understanding. Gemini can process and understand video clip frames to answer questions and generate descriptions. Multimodal reasoning. A key strength of Gemini is its use of multimodal AI reasoning, where different types of data can be mixed for a prompt to generate an output. Code analysis and generation. Gemini can understand, explain and generate code in popular programming languages, including Python, Java, C++ and Go. Applications Google developed Gemini as a foundation model to be widely integrated across various Google services. It's also available for developers to use in building their own applications. Applications that use Gemini include the following: AlphaCode 2. Google DeepMind's AlphaCode 2 code generation tool makes use of a customized version of Gemini Pro. Google Pixel. The Google-built Pixel 8 Pro smartphone is the first device engineered to run Gemini Nano. Gemini powers new features in existing Google apps, such as summarization in Recorder and Smart Reply in Gboard for messaging apps. Android 14. The Pixel 8 Pro is the first Android smartphone to benefit from Gemini. Android developers can build with Gemini Nano through the AICore system capability. Vertex AI. Google Cloud's Vertex AI service, which provides foundation models that developers can use to build applications, also provides access to Gemini Pro. Google AI Studio. Developers can build prototypes and apps with Gemini via the Google AI Studio web-based tool. Search. Google is experimenting with using Gemini in its Search Generative Experience to reduce latency and improve quality.

{Question} Summarize the possible uses, that are addressed in the provided document, of Google Gemini. ================ {Context} **What is Google Gemini (formerly Bard)?** Google Gemini -- formerly called Bard -- is an artificial intelligence (AI) chatbot tool designed by Google to simulate human conversations using natural language processing (NLP) and machine learning. In addition to supplementing Google Search, Gemini can be integrated into websites, messaging platforms or applications to provide realistic, natural language responses to user questions. List of tasks Google Gemini can perform. Google Gemini can be applied pragmatically to complete various tasks. Google Gemini is a family of multimodal AI large language models (LLMs) that have capabilities in language, audio, code and video understanding. Gemini 1.0 was announced on Dec. 6, 2023, and built by Alphabet's Google DeepMind business unit, which is focused on advanced AI research and development. Google co-founder Sergey Brin is credited with helping to develop the Gemini LLMs, alongside other Google staff. At its release, Gemini was the most advanced set of LLMs at Google, powering Bard before Bard's renaming and superseding the company's Pathways Language Model (Palm 2). As was the case with Palm 2, Gemini was integrated into multiple Google technologies to provide generative AI capabilities. Gemini integrates NLP capabilities, which provide the ability to understand and process language. Gemini is also used to comprehend input queries as well as data. It's able to understand and recognize images, enabling it to parse complex visuals, such as charts and figures, without the need for external optical character recognition (OCR). It also has broad multilingual capabilities for translation tasks and functionality across different languages. How does Google Gemini work? Google Gemini works by first being trained on a massive corpus of data. After training, the model uses several neural network techniques to be able to understand content, answer questions, generate text and produce outputs. Specifically, the Gemini LLMs use a transformer model-based neural network architecture. The Gemini architecture has been enhanced to process lengthy contextual sequences across different data types, including text, audio and video. Google DeepMind makes use of efficient attention mechanisms in the transformer decoder to help the models process long contexts, spanning different modalities. Gemini models have been trained on diverse multimodal and multilingual data sets of text, images, audio and video with Google DeepMind using advanced data filtering to optimize training. As different Gemini models are deployed in support of specific Google services, there's a process of targeted fine-tuning that can be used to further optimize a model for a use case. During both the training and inference phases, Gemini benefits from the use of Google's latest tensor processing unit chips, TPU v5, which are optimized custom AI accelerators designed to efficiently train and deploy large models. A key challenge for LLMs is the risk of bias and potentially toxic content. According to Google, Gemini underwent extensive safety testing and mitigation around risks such as bias and toxicity to help provide a degree of LLM safety. To help further ensure Gemini works as it should, the models were tested against academic benchmarks spanning language, image, audio, video and code domains. Google has assured the public it adheres to a list of AI principles. At launch on Dec. 6, 2023, Gemini was announced to be made up of a series of different model sizes, each designed for a specific set of use cases and deployment environments. The Ultra model is the top end and is designed for highly complex tasks. The Pro model is designed for performance and deployment at scale. As of Dec. 13, 2023, Google enabled access to Gemini Pro in Google Cloud Vertex AI and Google AI Studio. For code, a version of Gemini Pro is being used to power the Google AlphaCode 2 generative AI coding technology. The Nano model is targeted at on-device use cases. There are two different versions of Gemini Nano: Nano-1 is a 1.8 billion-parameter model, while Nano-2 is a 3.25 billion-parameter model. Among the places where Nano is being embedded is the Google Pixel 8 Pro smartphone. When was Google Bard first released? Google initially announced Bard, its AI-powered chatbot, on Feb. 6, 2023, with a vague release date. It opened access to Bard on March 21, 2023, inviting users to join a waitlist. On May 10, 2023, Google removed the waitlist and made Bard available in more than 180 countries and territories. Almost precisely a year after its initial announcement, Bard was renamed Gemini. Many believed that Google felt the pressure of ChatGPT's success and positive press, leading the company to rush Bard out before it was ready. For example, during a live demo by Google and Alphabet CEO Sundar Pichai, it responded to a query with a wrong answer. In the demo, a user asked Bard the question: "What new discoveries from the James Webb Space Telescope can I tell my 9-year-old about?" In Bard's response, it mentioned that the telescope "took the very first pictures of a planet outside of our own solar system." Astronomers quickly took to social media to point out that the first image of an exoplanet was taken by an earthbound observatory in 2004, making Bard's answer incorrect. The next day, Google lost $100 billion in market value -- a decline attributed to the embarrassing mistake. Why did Google rename Bard to Gemini and when did it happen? Bard was renamed Gemini on Feb. 8, 2024. Gemini was already the LLM powering Bard. Rebranding the platform as Gemini some believe might have been done to draw attention away from the Bard moniker and the criticism the chatbot faced when it was first released. It also simplified Google's AI effort and focused on the success of the Gemini LLM. The name change also made sense from a marketing perspective, as Google aims to expand its AI services. It's a way for Google to increase awareness of its advanced LLM offering as AI democratization and advancements show no signs of slowing. Who can use Google Gemini? Gemini is widely available around the world. Gemini Pro is available in more than 230 countries and territories, while Gemini Advanced is available in more than 150 countries at the time of this writing. However, there are age limits in place to comply with laws and regulations that exist to govern AI. Users must be at least 18 years old and have a personal Google account. However, age restrictions vary for the Gemini web app. Users in Europe must be 18 or older. In other countries where the platform is available, the minimum age is 13 unless otherwise specified by local laws. Also, users younger than 18 can only use the Gemini web app in English. Is Gemini free to use? When Bard became available, Google gave no indication that it would charge for use. Google has no history of charging customers for services, excluding enterprise-level usage of Google Cloud. The assumption was that the chatbot would be integrated into Google's basic search engine, and therefore be free to use. After rebranding Bard to Gemini on Feb. 8, 2024, Google introduced a paid tier in addition to the free web application. Pro and Nano currently are free to use via registration. However, users can only get access to Ultra through the Gemini Advanced option for $20 per month. Users sign up for Gemini Advanced through a Google One AI Premium subscription, which also includes Google Workspace features and 2 terabytes of storage. What can you use Gemini for? Use cases and applications The Google Gemini models are used in many different ways, including text, image, audio and video understanding. The multimodal nature of Gemini also enables these different types of input to be combined for generating output. Use cases Businesses can use Gemini to perform various tasks that include the following: Text summarization. Gemini models can summarize content from different types of data. Text generation. Gemini can generate text based on user prompts. That text can also be driven by a Q&A-type chatbot interface. Text translation. The Gemini models have broad multilingual capabilities, enabling translation and understanding of more than 100 languages. Image understanding. Gemini can parse complex visuals, such as charts, figures and diagrams, without external OCR tools. It can be used for image captioning and visual Q&A capabilities. Audio processing. Gemini has support for speech recognition across more than 100 languages and audio translation tasks. Video understanding. Gemini can process and understand video clip frames to answer questions and generate descriptions. Multimodal reasoning. A key strength of Gemini is its use of multimodal AI reasoning, where different types of data can be mixed for a prompt to generate an output. Code analysis and generation. Gemini can understand, explain and generate code in popular programming languages, including Python, Java, C++ and Go. Applications Google developed Gemini as a foundation model to be widely integrated across various Google services. It's also available for developers to use in building their own applications. Applications that use Gemini include the following: AlphaCode 2. Google DeepMind's AlphaCode 2 code generation tool makes use of a customized version of Gemini Pro. Google Pixel. The Google-built Pixel 8 Pro smartphone is the first device engineered to run Gemini Nano. Gemini powers new features in existing Google apps, such as summarization in Recorder and Smart Reply in Gboard for messaging apps. Android 14. The Pixel 8 Pro is the first Android smartphone to benefit from Gemini. Android developers can build with Gemini Nano through the AICore system capability. Vertex AI. Google Cloud's Vertex AI service, which provides foundation models that developers can use to build applications, also provides access to Gemini Pro. Google AI Studio. Developers can build prototypes and apps with Gemini via the Google AI Studio web-based tool. Search. Google is experimenting with using Gemini in its Search Generative Experience to reduce latency and improve quality. ================ {Task Information} Refer only to the context document in your answer. Do not employ any outside information. Use complete sentences.

Base your answer purely in the provided context. Answer in only one sentence.

Based only on the article provided, what is the difference between how SoundCloud's recommendation algorithm works and those of other streaming services?

**WHAT’S NEW WITH SOUNDCLOUD IN FEBRUARY: CARPLAY, 2FA, AND MORE** As winter is winding down, we’re starting to get hot. Read on for more information about our latest launches and updates to SoundCloud. In case you missed it: Apple CarPlay is here Road trips just got better: SoundCloud is available on Apple Carplay for Go, Go+, and Next Pro subscribers. Protect your account with 2FA We know how much time it took to create that track or curate that perfect playlist. At SoundCloud, we love people who love music and are committed to keeping their data as safe as possible. That’s why your security is such a priority to us, and why we’re encouraging you to up your security game by enabling two-factor authorization (2FA). After pairing your device with a 2FA app, you will now be asked to enter a quick security code whenever you log in to your account to prove it’s you, not a bot or hacker. Learn how to enable two-factor authentication here. Refreshed music algorithms and recommendations Most streaming services recommend tracks based on what similar people are listening to. If someone similar to me listens to and likes “Fred Again”, chances are I’ll be recommended “Fred Again”. That obviously works well for artists who are already being heard. But what about all of the songs that don’t have any plays yet? Well, that’s exactly the problem with most music algorithms. They simply can’t recommend tracks with zero plays. If no one has listened yet, they’ve got no signals. Next Pro changes the game. Using AI, we can quickly analyze tracks and surface them to listeners who are likely to enjoy them. Even if they were just uploaded and have zero plays. If you’re not already on Next Pro, sign up today and get your first 100 plays. Bulk edits in Track Manager page We recently updated the Track Manager to make the creator workflow more intuitive and easy. Now, you can bulk edit multiple tracks at once, add tracks to playlists, and quickly edit a single track. It’s part of a greater revamp to improve our web experience and refresh our product over the coming months, so watch this space. Removal of Sync with SoundCloud We removed a massive amount of friction and frustration within the “Monetize” tab. Previously artists had to manually push a button to sync the data to see their tracks, resulting in confusion. Now, tracks are automatically synced. Stay tuned and make sure to follow us at @SCSupport for the latest.

<query> ========== Based only on the article provided, what is the difference between how SoundCloud's recommendation algorithm works and those of other streaming services? ---------------- <task instructions> ========== Base your answer purely in the provided context. Answer in only one sentence. ---------------- <text passage> ========== **WHAT’S NEW WITH SOUNDCLOUD IN FEBRUARY: CARPLAY, 2FA, AND MORE** As winter is winding down, we’re starting to get hot. Read on for more information about our latest launches and updates to SoundCloud. In case you missed it: Apple CarPlay is here Road trips just got better: SoundCloud is available on Apple Carplay for Go, Go+, and Next Pro subscribers. Protect your account with 2FA We know how much time it took to create that track or curate that perfect playlist. At SoundCloud, we love people who love music and are committed to keeping their data as safe as possible. That’s why your security is such a priority to us, and why we’re encouraging you to up your security game by enabling two-factor authorization (2FA). After pairing your device with a 2FA app, you will now be asked to enter a quick security code whenever you log in to your account to prove it’s you, not a bot or hacker. Learn how to enable two-factor authentication here. Refreshed music algorithms and recommendations Most streaming services recommend tracks based on what similar people are listening to. If someone similar to me listens to and likes “Fred Again”, chances are I’ll be recommended “Fred Again”. That obviously works well for artists who are already being heard. But what about all of the songs that don’t have any plays yet? Well, that’s exactly the problem with most music algorithms. They simply can’t recommend tracks with zero plays. If no one has listened yet, they’ve got no signals. Next Pro changes the game. Using AI, we can quickly analyze tracks and surface them to listeners who are likely to enjoy them. Even if they were just uploaded and have zero plays. If you’re not already on Next Pro, sign up today and get your first 100 plays. Bulk edits in Track Manager page We recently updated the Track Manager to make the creator workflow more intuitive and easy. Now, you can bulk edit multiple tracks at once, add tracks to playlists, and quickly edit a single track. It’s part of a greater revamp to improve our web experience and refresh our product over the coming months, so watch this space. Removal of Sync with SoundCloud We removed a massive amount of friction and frustration within the “Monetize” tab. Previously artists had to manually push a button to sync the data to see their tracks, resulting in confusion. Now, tracks are automatically synced. Stay tuned and make sure to follow us at @SCSupport for the latest.

Use only the information provided in the Prompt to answer any questions. You may not use any previous knowledge or external resources. Limit your answer to a maximum of 150 words.

Please summarize the given text into two paragraphs at most, and do not include multiple subheadings; all of the information should be under a singular title.

Program Caps Program caps, sometimes called aggregate capacity limits, set limits on the number of customers or amount of generation capacity that may participate. Program caps can be expressed in units of power (e.g., megawatts; MW),39 a percentage of electricity demand over some period of time, or other measures as determined by a state. The choice of whether to have program caps and, if so, how to define them can affect the amount of DG that a state’s net metering policy might promote.40 Program caps may be established to reduce risks to the electricity system, such as potential reliability risks from DG, or reduce the likelihood that cross-subsidies would occur. Caps also might reduce the potential for sales losses or other negative financial impacts for utilities.41 On the other hand, program caps might create a barrier to achieving other policy goals, for example the renewable energy goals that some states have. Source Eligibility States specify which generation sources can participate in net metering, often based on capacity limits (i.e., generator size) and technology type. Solar energy is the dominant energy source for net metering capacity, but some states allow other energy types to participate as well. Whether a non-solar project will participate is usually due to cost factors, but other factors such as customer type (e.g., residential, commercial, or industrial) and location (e.g., urban, rural) may be influential as well. For example, combined heat and power facilities might be attractive mostly to large commercial and industrial customers that use steam. Distributed wind projects might be attractive mostly to farms or other customers with relatively large acreage.

Use only the information provided in the Prompt to answer any questions. You may not use any previous knowledge or external resources. Limit your answer to a maximum of 150 words. Please summarize the given text into two paragraphs at most, and do not include multiple subheadings; all of the information should be under a singular title. Program Caps Program caps, sometimes called aggregate capacity limits, set limits on the number of customers or amount of generation capacity that may participate. Program caps can be expressed in units of power (e.g., megawatts; MW),39 a percentage of electricity demand over some period of time, or other measures as determined by a state. The choice of whether to have program caps and, if so, how to define them can affect the amount of DG that a state’s net metering policy might promote.40 Program caps may be established to reduce risks to the electricity system, such as potential reliability risks from DG, or reduce the likelihood that cross-subsidies would occur. Caps also might reduce the potential for sales losses or other negative financial impacts for utilities.41 On the other hand, program caps might create a barrier to achieving other policy goals, for example the renewable energy goals that some states have. Source Eligibility States specify which generation sources can participate in net metering, often based on capacity limits (i.e., generator size) and technology type. Solar energy is the dominant energy source for net metering capacity, but some states allow other energy types to participate as well. Whether a non-solar project will participate is usually due to cost factors, but other factors such as customer type (e.g., residential, commercial, or industrial) and location (e.g., urban, rural) may be influential as well. For example, combined heat and power facilities might be attractive mostly to large commercial and industrial customers that use steam. Distributed wind projects might be attractive mostly to farms or other customers with relatively large acreage.

Provide a response using only information in the context block. Limit the response to 300 words.

Based on the context, would an owner of a business owning less than 10% of an insurance company regulated by the state of New Jersey be considered a legal entity customer and/or be required to report the identity of the beneficial owner?

Under the Beneficial Ownership Rule, 1 a bank must establish and maintain written procedures that are reasonably designed to identify and verify beneficial owner(s) of legal entity customers and to include such procedures in its anti-money laundering compliance program. Legal entities, whether domestic or foreign, can be used to facilitate money laundering and other crimes because their true ownership can be concealed. The collection of beneficial ownership information by banks about legal entity customers can provide law enforcement with key details about suspected criminals who use legal entity structures to conceal their illicit activity and assets. Requiring legal entity customers seeking access to banks to disclose identifying information, such as the name, date of birth, and Social Security number of natural persons who own or control them will make such entities more transparent, and thus less attractive to criminals and those who assist them. Similar to other customer information that a bank may gather, beneficial ownership information collected under the rule may be relevant to other regulatory requirements. These other regulatory requirements include, but are not limited to, identifying suspicious activity, and determining Office of Foreign Assets Control (OFAC) sanctioned parties. Banks should define in their policies, procedures, and processes how beneficial ownership information will be used to meet other regulatory requirements. Legal Entity Customers For the purposes of the Beneficial Ownership Rule, 2 a legal entity customer is defined as a corporation, limited liability company, or other entity that is created by the filing of a public document with a Secretary of State or other similar office, a general partnership, and any similar entity formed under the laws of a foreign jurisdiction that opens an account. A number of types of business entities are excluded from the definition of legal entity customer under the Beneficial Ownership rule. In addition, and subject to certain limitations, banks are not required to identify and verify the identity of the beneficial owner(s) of a legal entity customer when the customer opens certain types of accounts. For further information on exclusions and exemptions to the Beneficial Ownership Rule, see Appendix 1. These exclusions and exemptions do not alter or supersede other existing requirements related to BSA/AML and OFAC sanctions. Beneficial Owner(s) Beneficial ownership is determined under both a control prong and an ownership prong. Under the control prong, the beneficial owner is a single individual with significant responsibility to control, manage or direct a legal entity customer.3 This includes, an executive officer or senior manager (Chief Executive Officer, Chief Financial Officer, Chief Operating Officer, President), or any other individual who regularly performs similar functions. One beneficial owner must be identified under the control prong for each legal entity customer. Under the ownership prong, a beneficial owner is each individual, if any, who, directly or indirectly, through any contract, arrangement, understanding, relationship or otherwise, owns 25 percent or more of the equity interests of a legal entity customer.4 If a trust owns directly or indirectly, through any contract, arrangement, understanding, relationship or otherwise, 25 percent or more of the equity interests of a legal entity customer, the beneficial owner is the trustee.5 Identification of a beneficial owner under the ownership prong is not required if no individual owns 25 percent or more of a legal entity customer. Therefore, all legal entity customers will have a total of between one and five beneficial owner(s) – one individual under the control prong and zero to four individuals under the ownership prong. Exclusions from the definition of Legal Entity Customer Under 31 CFR 1010.230(e)(2) a legal entity customer does not include: • A financial institution regulated by a federal functional regulator14 or a bank regulated by a state bank regulator; • A person described in 31 CFR 1020.315(b)(2) through (5): o A department or agency of the United States, of any state, or of any political subdivision of any State; o Any entity established under the laws of the United States, of any state, or of any political subdivision of any state, or under an interstate compact between two or more states, that exercises governmental authority on behalf of the United States or any such state or political subdivision; o Any entity (other than a bank) whose common stock or analogous equity interests are listed on the New York Stock Exchange or the American Stock Exchange (currently known as the NYSE American) or have been designated as a NASDAQ National Market Security listed on the NASDAQ stock exchange (with some exceptions); o Any subsidiary (other than a bank) of any “listed entity” that is organized under the laws of the United States or of any state and at least 51 percent of whose common stock or analogous equity interest is owned by the listed entity, provided that a person that is a financial institution, other than a bank, is an exempt person only to the extent of its domestic operations; • An issuer of a class of securities registered under section 12 of the Securities Exchange Act of 1934 or that is required to file reports under section 15(d) of that Act; • An investment company, investment adviser, an exchange or clearing agency, or any other entity that is registered with the SEC; • A registered entity, commodity pool operator, commodity trading advisor, retail foreign exchange dealer, swap dealer, or major swap participant that is registered with the CFTC; • A public accounting firm registered under section 102 of the Sarbanes-Oxley Act; • A bank holding company or savings and loan holding company; • A pooled investment vehicle that is operated or advised by a financial institution that is excluded under paragraph (e)(2); • An insurance company that is regulated by a state;

Provide a response using only information in the context block. Limit the response to 300 words. Based on the context, would an owner of a business owning less than 10% of an insurance company regulated by the state of New Jersey be considered a legal entity customer and/or be required to report the identity of the beneficial owner? Under the Beneficial Ownership Rule, 1 a bank must establish and maintain written procedures that are reasonably designed to identify and verify beneficial owner(s) of legal entity customers and to include such procedures in its anti-money laundering compliance program. Legal entities, whether domestic or foreign, can be used to facilitate money laundering and other crimes because their true ownership can be concealed. The collection of beneficial ownership information by banks about legal entity customers can provide law enforcement with key details about suspected criminals who use legal entity structures to conceal their illicit activity and assets. Requiring legal entity customers seeking access to banks to disclose identifying information, such as the name, date of birth, and Social Security number of natural persons who own or control them will make such entities more transparent, and thus less attractive to criminals and those who assist them. Similar to other customer information that a bank may gather, beneficial ownership information collected under the rule may be relevant to other regulatory requirements. These other regulatory requirements include, but are not limited to, identifying suspicious activity, and determining Office of Foreign Assets Control (OFAC) sanctioned parties. Banks should define in their policies, procedures, and processes how beneficial ownership information will be used to meet other regulatory requirements. Legal Entity Customers For the purposes of the Beneficial Ownership Rule, 2 a legal entity customer is defined as a corporation, limited liability company, or other entity that is created by the filing of a public document with a Secretary of State or other similar office, a general partnership, and any similar entity formed under the laws of a foreign jurisdiction that opens an account. A number of types of business entities are excluded from the definition of legal entity customer under the Beneficial Ownership rule. In addition, and subject to certain limitations, banks are not required to identify and verify the identity of the beneficial owner(s) of a legal entity customer when the customer opens certain types of accounts. For further information on exclusions and exemptions to the Beneficial Ownership Rule, see Appendix 1. These exclusions and exemptions do not alter or supersede other existing requirements related to BSA/AML and OFAC sanctions. Beneficial Owner(s) Beneficial ownership is determined under both a control prong and an ownership prong. Under the control prong, the beneficial owner is a single individual with significant responsibility to control, manage or direct a legal entity customer.3 This includes, an executive officer or senior manager (Chief Executive Officer, Chief Financial Officer, Chief Operating Officer, President), or any other individual who regularly performs similar functions. One beneficial owner must be identified under the control prong for each legal entity customer. Under the ownership prong, a beneficial owner is each individual, if any, who, directly or indirectly, through any contract, arrangement, understanding, relationship or otherwise, owns 25 percent or more of the equity interests of a legal entity customer.4 If a trust owns directly or indirectly, through any contract, arrangement, understanding, relationship or otherwise, 25 percent or more of the equity interests of a legal entity customer, the beneficial owner is the trustee.5 Identification of a beneficial owner under the ownership prong is not required if no individual owns 25 percent or more of a legal entity customer. Therefore, all legal entity customers will have a total of between one and five beneficial owner(s) – one individual under the control prong and zero to four individuals under the ownership prong. Exclusions from the definition of Legal Entity Customer Under 31 CFR 1010.230(e)(2) a legal entity customer does not include: • A financial institution regulated by a federal functional regulator14 or a bank regulated by a state bank regulator; • A person described in 31 CFR 1020.315(b)(2) through (5): o A department or agency of the United States, of any state, or of any political subdivision of any State; o Any entity established under the laws of the United States, of any state, or of any political subdivision of any state, or under an interstate compact between two or more states, that exercises governmental authority on behalf of the United States or any such state or political subdivision; o Any entity (other than a bank) whose common stock or analogous equity interests are listed on the New York Stock Exchange or the American Stock Exchange (currently known as the NYSE American) or have been designated as a NASDAQ National Market Security listed on the NASDAQ stock exchange (with some exceptions); o Any subsidiary (other than a bank) of any “listed entity” that is organized under the laws of the United States or of any state and at least 51 percent of whose common stock or analogous equity interest is owned by the listed entity, provided that a person that is a financial institution, other than a bank, is an exempt person only to the extent of its domestic operations; • An issuer of a class of securities registered under section 12 of the Securities Exchange Act of 1934 or that is required to file reports under section 15(d) of that Act; • An investment company, investment adviser, an exchange or clearing agency, or any other entity that is registered with the SEC; • A registered entity, commodity pool operator, commodity trading advisor, retail foreign exchange dealer, swap dealer, or major swap participant that is registered with the CFTC; • A public accounting firm registered under section 102 of the Sarbanes-Oxley Act; • A bank holding company or savings and loan holding company; • A pooled investment vehicle that is operated or advised by a financial institution that is excluded under paragraph (e)(2); • An insurance company that is regulated by a state;

Use only the document provided and nothing else.

What is the RMS delay spread with a 30° antenna beam width compared to an omnidirectional antenna?

International Journal of Engineering Inventions ISSN: 2278-7461, www.ijeijournal.com Volume 1, Issue 3 (September 2012) PP: 06-11 Bit Error Rate of Mobile Wimax (Phy) Under Different Communication Channels and Modulation Technique T.Manochandar 1 , R.Krithika 2 'Department of Electronics and Communication Engineering, VRS College of engineering and technology, Villupuram- 607 107 '.TamilNadu 2 Department of Electronics and Communication Engineering, E.S College oj < I in , , "• and technology, ViUupuram-605 602. TamilNadu Abstract — Mobile Wimax is a broadband wireless solution that enables the convergence of mobile and fixed broadband network, through a common wide area broadband radio access technology and flexible network architecture. The Performance of mobile Wimax under varying channel is one of the interesting research interests. Most of the most existing systems, based on performance and evaluation under channel condition are limited to AWGN, ITU etc in mobile Wimax. In this paper the performance of mobile Wimax (PHY layer) under SUI channel models in addition to different data rates and modulation techniques were analyzed. The simulation cavers important performance parameters like Bit Error Rate and Signal to Noise Ratio. Keywords— Wimax, BER, SNR, BPSK, OFDMA I. INTRODUCTION IEEE802.16e is a global broadband wireless access standard capable of delivering high data rates to fixed users as well as portable and mobile ones over long distance [l].In mobile Wimax air interface adopts orthogonal frequency division multiple access (OFDMA) for improved multi-path performance in non-line-of sight (NLOS) environment. Mobile Wimax extends the OFDM PHY layer to support terminal mobility and multiple-access. The resulting technology is Scalable OFDMA. Data streams to and from indh idual users are multiplexed to groups of sub channel on the downlink and uplink. By adopting Scalable PHY architecture, mobile Wimax is able to support a wide range of bandwidths. The performance of the WiMAX (Worldwide Interoperability for Microwave Access) can be evaluated by using the Stanford University Interim (SUI) channel models which has a set of six channels for terrain types [3J.With different data rates, coding schemes and modulation techniques. The mobile WiMAX standard builds on the principles of OFDM by adopting a Scalable OFDMA-based PHY layer (SOFDMA) [4J. SOFDMA supports a wide range of operating bandwidths to flexibl) address the need for various spectrum allocation and application requirements. The simulation done in the paper covers important performance such as Bit Error Rate and Signal to Noise Ratio. II. WIMAX PHYSICAL LAYER This project deals with the performances of Bit Error Rate and Signal to Noise Ratio in mobile WiMAX physical layer. The block diagram of the physical layer of mobile WiMAX diagram is given in Figure 1 . The transferring of data or receiving the data is done through the physical layer of WiMAX. So the uplink and the downlink of the message were done on the physical layer of WiMAX. There are three levels in the physical layer of mobile WiMAX physical layer are • Bit level processing • OFDM symbol level processing • Digital IF processing Each levels of physical layer of WiMAX consist of certain processes for transferring the data at uplink region and receiving of data at downlink region consists of encoder, decoder, symbol mapper and randomizer etc., Every processes were done in order to improve the performance of the mobility condition of mobile wimax. In this paper the perfor analyzed by the signal to noise ratio and the bit error rate Bit Error Rale Of Mobile Wimax (Plix) Under Different Communication,,, m^v Figure: 1. Block Diagram of Wimax Physical Layer Table. 1 Parameter of mobile wima x physical layer Parameter Value FFT size 128 512 1024 2048 Channel Bandwidth(MHz) 1.25 5 10 20 Subcarrier Frequency spacing (KHz) 10.94 Useful Symbol Period 91.4 Guard Time 1/32,1/8,1/6,1/4 III. CHANNEL The medium between the transmitting antenna and the receiving antenna is said to be the channel. The profile of received signal can be obtained from that of the transmitted signal, if we have a model of the medium between the two. The model of the medium is called channel model. Bit Error Rate Of Mobile Winuix (Plix) Under Different Communication... Y (f) ->oulpui signal H (f) ->channel response X (f) ->input signal Y (f) =X (f) H (f) +n (f) A. Stanford Universit) [nterim (SUI) Channel Models: It is a set of six channel models representing three terrain types and a variety of Doppler spreads, delay spread and mainly the line-of-sight/non-line-of-site conditions that are typical of the continental. The terrain type A, B, C is same as those defined in Erceg model [10]. The multipath fading is modeled as a tapped delay line with 3 taps with non-uniform delays. The gain associated w ith each tap is characterized by a Rician Distribution and the maximum Doppler frequency. In a multipath environment, the received power r has a Rician distribution, whose Pdf is given by: o LOS component and the pdf of the power becomes Pdf(r)=r/o 2 e [ -* ac2+A2a2] Io(rA/o 2 ) < r < a This is also known as Raleigh distribution. The ratio K=A / (2o2) in the Rician case represents the ratio of LOS component to NLOS component and is called the "K- Factor" or "Rician Factor." The general structure for the SUI channel model is as shown below in figure. This structure is for Multiple Input Multiple Output (MIMO) channels and includes other configurations like Single Input Single Output (SISO) and Single Input Multiple Output (SIMO) as subsets. Figure 2.SUI Channel Model Power Distribution For each tap a set of complex zero-mean Gaussian distributed numbers is generated with a e of 0.5 for the real and imaginary part, so that the total average power of this distribution is 1. This yields a normalized Rayleigh distribution (equivalent to Rice with K=0) for the magnitude of the complex coefficients. If a Rician distribution (K>0 implied) is needed, a constant path component m is added to the Rayleigh set of coefficients. The ratio of powers between this constant part and the Rayleigh (variable) part is specified by the K-factor. For this general case, we show how to distribute the power correctly by first stating die total power P of each tap: Where m is the comple: of the complex Gaussian set. Second, the ratio of powers is K=m 2 /|o 2 l. T able 2: Terrain type and Doppler spread for SUI channel mod el Channel Terrain Type spread Spread LOS SUI-1 C Low Low High SUI-2 C Low Low High SUI-3 B Low Low Low SUI-4 B High Moderate Low SUI-5 A Low High Low SUI-6 A High High High Bit Error Rale Of Mobile Wimax (Phy) Under Different Communication... In the SUI channel model, parameter for the SUI 1 and SUI 2 channel model has been tabulated in 3 and 4 respectively for the reference. BER performance is evaluated in this channel models. Depending on the performance parameter for the SUI channel, the performances of wimax physical layer are evaluated through the performance graph. Table 3 SUI -1 Channel Model Tapl Tap 2 Tap 3 Units Delay 0.4 0.9 [IS Power(omni antenna) 90% K-facto<omni) 0<OIM 4 20 -15 -20 db Power(30 antenna) 90% k-facto<30°) 16 72 -21 -32 db Doppler 0.4 0.3 0.5 Hz < , - , iii Gain Reduction Factor: GRF=0db Normalisation Factor: F^i=-0.1771db FV=-0.0371db Terrain Type : C Omni antenna :tems = 0.1 11 [is Overall K:K=3 .3 (90%) K= .10.4(75%) 30 u 3iitenna:i[j!]Ms =0.042 \is Overall K:K= 14. 0(90%) K=44 2(7 4>) Table 4 SUI -2 Channel Mo del Tapl Tap 2 3 Units Delay 0.4 1.1 us Power(ortmi antenna) 90% K-facto<omni) 73% K-facto<omni) 11 -12 -15 db Poweri i0' minni i 90% k-facto<30°) 75% K-facto<30*) 36" -27 db Doppler 0.2 0.15 0.25 Hz Antenna c on elation. p= . '. O am Re duction F actor: GRF =2 db Normalization Factor: F Mmi =-0.3930db F 3 o°=- n .07(58clb Terrain Type : C Omni antenna : tbke = 0.202 us Overall K: K=l .6 (90%) K=5.1(75%) 30 antenna:T EWS =0.06QLS Overall K:K=<5 .9(90%) K=21.S(75%) For a 30° antenna beam width, 2.3 times smaller RMS delay spread is used when compared to an omnidirectional antenna RMS delay spread. Consequently, the 2nd tap power is attenuated additional 6 dB and the 3rd tap power is attenuated additional 12 dB (effect of antenna pattern, delays remain the same). The simulation results for all the six channels arc e\ aluated. The above experiments are done using the simulation in Matlab communication tool box. IV. The output for the perfc MATLAB coding with BPSK modulati SIMULATION RESULTS of mobile WiMAX was estimated by the BER and the SNR plot t The bandwidth used in the experiment was 3.5 MHz Bit Error Rate Of Mobile Wima.x (Phy) Under Different Communication... Figure3.BER curve for BPSK modulation The output for the performance of mobile WiMAX was estimated by the Bit Error Rate and the Signal to Noise Ratio plot using the MATLAB coding with Quadrature Phase Shift Keying modulation technique is given below in figure 4. BER of the received symbols. ( G=0.25.BW=3.5MHz and modulation of QPSK ) Figure 4. BER curve for QPSK modulation The output for the performance of mobile WiMAX was estimated by the BER and the SNR plot using the MATLAB coding with 16QAM modulation. It is illustrated in the figure5. Figure5. BER curve for 16QAM modulation Bit Error Rate Of Mobile Wimax (Phy) Under Different Communication... The output for the performance of mobile Wimax was estimated by the BER and the SNR plot using the MATLAB coding with 64QAM modulation and graphical illustration done as in figure 6. Figure6. BER curve for 64QAM modulation V. CONCLUSION In this paper, the performance of mobile WIMAX physical layer for OFDMA on different channel condition assisted by Mobile IP(Internet protocol) for mobility management was analyzed. The analysis demonstrated that the modulation and coding rate had a greater impact on the relative performance between the different SU1 channel conditions. The performance was analyzed under SUI channel models with different modulation techniques for mobility management. It is found from the performance graphs that SUI channel 5 and 6 performs better than the conventional ones. REFERENCES IEEE 2010 Omar Arafat,K.Dimyati, a study of physical layer of Mobile WiMax under different communication channels & modulation technique. [2JIEEE std 802.16 Etm-2004"Part 16: Air Interface for fixed and mobile broadband wireless Access system,"Feb 2004. Md.ZahidHasan.Mu.A .hiaiiillslam, Comparative Study of Different Guard Time Intervals to Improve the BER Performance of WiM AX Systems to Minimize the Effects of ISI and 1CI under Adaptive Modulation Techniques over SUI-1 and AWGN Communication Channels, (IICSIS) International Journal of Computer Science and Information Security, Vol. 6, No.2, 2009. IEEE 802.16 Broadband Wireless Access Working Group Simulating the SUI Channel Models Li-Chun Wang Department of Communications Engineering National Chiao Tung University Hsinchu,Taiwan. Mai Tran, G Zaggaoulos and A .Nix" Mobile WiMAX MIMO performance Analysis: Downlink and Uplink", PIMRC2008. J.GAndews, A.Ghoshand R.Muhamed, Fundamentals of WiMAX Understanding broadband Wireless Networks, "Prentice Hall, Feb 2007. RajJain,@aum.org,"ChannelModelaTutorial", feb21,2007 submitted to wimax forum at aum. M.S. Smith and C. Tappenden, 'Additional enhancements to interim channel models for G2 MMDS fixed wireless applications," IEEE 802.16.3c-00/53 M.S.Smith, J.E.J. Dalley, "A new methodology for deriving path loss models from cellular drive test data", Proc.AP2000 Conference, Davos, Switzerland, April 2000. V. Erceget.al, "A model for the multipath delay profile of fixed wireless channels," IEEE JSAC, vol. 17, no. 3, March 1999, pp. 399-410. L.J.Greenstein, V. Erceg, Y.S. Yeh, and M.V. Clark, "A new path-gain/delay-spread propagation model for digital cellular channels," IEEE Trans. Veh. Technol., vol. 46, no. 2, May 1997. J.W. Porter and J.A. Thweatt, "Microwave propagation characteristics in the MMDS frequency band," ICC'2000 Conference Proceedings, pp. 1578-1582. L.J. Greenstein, S. Ghassemzadeh, V.Erceg, and DG. Michelson, "Ricean K-factors in narrowband fixed wireless channels: Theory, experiments, and statistical models," WPMC'99 Conference Proceedings, Amsterdam, September 1999.

Use only the document provided and nothing else. What is the RMS delay spread with a 30° antenna beam width compared to an omnidirectional antenna? International Journal of Engineering Inventions ISSN: 2278-7461, www.ijeijournal.com Volume 1, Issue 3 (September 2012) PP: 06-11 Bit Error Rate of Mobile Wimax (Phy) Under Different Communication Channels and Modulation Technique T.Manochandar 1 , R.Krithika 2 'Department of Electronics and Communication Engineering, VRS College of engineering and technology, Villupuram- 607 107 '.TamilNadu 2 Department of Electronics and Communication Engineering, E.S College oj < I in , , "• and technology, ViUupuram-605 602. TamilNadu Abstract — Mobile Wimax is a broadband wireless solution that enables the convergence of mobile and fixed broadband network, through a common wide area broadband radio access technology and flexible network architecture. The Performance of mobile Wimax under varying channel is one of the interesting research interests. Most of the most existing systems, based on performance and evaluation under channel condition are limited to AWGN, ITU etc in mobile Wimax. In this paper the performance of mobile Wimax (PHY layer) under SUI channel models in addition to different data rates and modulation techniques were analyzed. The simulation cavers important performance parameters like Bit Error Rate and Signal to Noise Ratio. Keywords— Wimax, BER, SNR, BPSK, OFDMA I. INTRODUCTION IEEE802.16e is a global broadband wireless access standard capable of delivering high data rates to fixed users as well as portable and mobile ones over long distance [l].In mobile Wimax air interface adopts orthogonal frequency division multiple access (OFDMA) for improved multi-path performance in non-line-of sight (NLOS) environment. Mobile Wimax extends the OFDM PHY layer to support terminal mobility and multiple-access. The resulting technology is Scalable OFDMA. Data streams to and from indh idual users are multiplexed to groups of sub channel on the downlink and uplink. By adopting Scalable PHY architecture, mobile Wimax is able to support a wide range of bandwidths. The performance of the WiMAX (Worldwide Interoperability for Microwave Access) can be evaluated by using the Stanford University Interim (SUI) channel models which has a set of six channels for terrain types [3J.With different data rates, coding schemes and modulation techniques. The mobile WiMAX standard builds on the principles of OFDM by adopting a Scalable OFDMA-based PHY layer (SOFDMA) [4J. SOFDMA supports a wide range of operating bandwidths to flexibl) address the need for various spectrum allocation and application requirements. The simulation done in the paper covers important performance such as Bit Error Rate and Signal to Noise Ratio. II. WIMAX PHYSICAL LAYER This project deals with the performances of Bit Error Rate and Signal to Noise Ratio in mobile WiMAX physical layer. The block diagram of the physical layer of mobile WiMAX diagram is given in Figure 1 . The transferring of data or receiving the data is done through the physical layer of WiMAX. So the uplink and the downlink of the message were done on the physical layer of WiMAX. There are three levels in the physical layer of mobile WiMAX physical layer are • Bit level processing • OFDM symbol level processing • Digital IF processing Each levels of physical layer of WiMAX consist of certain processes for transferring the data at uplink region and receiving of data at downlink region consists of encoder, decoder, symbol mapper and randomizer etc., Every processes were done in order to improve the performance of the mobility condition of mobile wimax. In this paper the perfor analyzed by the signal to noise ratio and the bit error rate Bit Error Rale Of Mobile Wimax (Plix) Under Different Communication,,, m^v Figure: 1. Block Diagram of Wimax Physical Layer Table. 1 Parameter of mobile wima x physical layer Parameter Value FFT size 128 512 1024 2048 Channel Bandwidth(MHz) 1.25 5 10 20 Subcarrier Frequency spacing (KHz) 10.94 Useful Symbol Period 91.4 Guard Time 1/32,1/8,1/6,1/4 III. CHANNEL The medium between the transmitting antenna and the receiving antenna is said to be the channel. The profile of received signal can be obtained from that of the transmitted signal, if we have a model of the medium between the two. The model of the medium is called channel model. Bit Error Rate Of Mobile Winuix (Plix) Under Different Communication... Y (f) ->oulpui signal H (f) ->channel response X (f) ->input signal Y (f) =X (f) H (f) +n (f) A. Stanford Universit) [nterim (SUI) Channel Models: It is a set of six channel models representing three terrain types and a variety of Doppler spreads, delay spread and mainly the line-of-sight/non-line-of-site conditions that are typical of the continental. The terrain type A, B, C is same as those defined in Erceg model [10]. The multipath fading is modeled as a tapped delay line with 3 taps with non-uniform delays. The gain associated w ith each tap is characterized by a Rician Distribution and the maximum Doppler frequency. In a multipath environment, the received power r has a Rician distribution, whose Pdf is given by: o LOS component and the pdf of the power becomes Pdf(r)=r/o 2 e [ -* ac2+A2a2] Io(rA/o 2 ) < r < a This is also known as Raleigh distribution. The ratio K=A / (2o2) in the Rician case represents the ratio of LOS component to NLOS component and is called the "K- Factor" or "Rician Factor." The general structure for the SUI channel model is as shown below in figure. This structure is for Multiple Input Multiple Output (MIMO) channels and includes other configurations like Single Input Single Output (SISO) and Single Input Multiple Output (SIMO) as subsets. Figure 2.SUI Channel Model Power Distribution For each tap a set of complex zero-mean Gaussian distributed numbers is generated with a e of 0.5 for the real and imaginary part, so that the total average power of this distribution is 1. This yields a normalized Rayleigh distribution (equivalent to Rice with K=0) for the magnitude of the complex coefficients. If a Rician distribution (K>0 implied) is needed, a constant path component m is added to the Rayleigh set of coefficients. The ratio of powers between this constant part and the Rayleigh (variable) part is specified by the K-factor. For this general case, we show how to distribute the power correctly by first stating die total power P of each tap: Where m is the comple: of the complex Gaussian set. Second, the ratio of powers is K=m 2 /|o 2 l. T able 2: Terrain type and Doppler spread for SUI channel mod el Channel Terrain Type spread Spread LOS SUI-1 C Low Low High SUI-2 C Low Low High SUI-3 B Low Low Low SUI-4 B High Moderate Low SUI-5 A Low High Low SUI-6 A High High High Bit Error Rale Of Mobile Wimax (Phy) Under Different Communication... In the SUI channel model, parameter for the SUI 1 and SUI 2 channel model has been tabulated in 3 and 4 respectively for the reference. BER performance is evaluated in this channel models. Depending on the performance parameter for the SUI channel, the performances of wimax physical layer are evaluated through the performance graph. Table 3 SUI -1 Channel Model Tapl Tap 2 Tap 3 Units Delay 0.4 0.9 [IS Power(omni antenna) 90% K-facto<omni) 0<OIM 4 20 -15 -20 db Power(30 antenna) 90% k-facto<30°) 16 72 -21 -32 db Doppler 0.4 0.3 0.5 Hz < , - , iii Gain Reduction Factor: GRF=0db Normalisation Factor: F^i=-0.1771db FV=-0.0371db Terrain Type : C Omni antenna :tems = 0.1 11 [is Overall K:K=3 .3 (90%) K= .10.4(75%) 30 u 3iitenna:i[j!]Ms =0.042 \is Overall K:K= 14. 0(90%) K=44 2(7 4>) Table 4 SUI -2 Channel Mo del Tapl Tap 2 3 Units Delay 0.4 1.1 us Power(ortmi antenna) 90% K-facto<omni) 73% K-facto<omni) 11 -12 -15 db Poweri i0' minni i 90% k-facto<30°) 75% K-facto<30*) 36" -27 db Doppler 0.2 0.15 0.25 Hz Antenna c on elation. p= . '. O am Re duction F actor: GRF =2 db Normalization Factor: F Mmi =-0.3930db F 3 o°=- n .07(58clb Terrain Type : C Omni antenna : tbke = 0.202 us Overall K: K=l .6 (90%) K=5.1(75%) 30 antenna:T EWS =0.06QLS Overall K:K=<5 .9(90%) K=21.S(75%) For a 30° antenna beam width, 2.3 times smaller RMS delay spread is used when compared to an omnidirectional antenna RMS delay spread. Consequently, the 2nd tap power is attenuated additional 6 dB and the 3rd tap power is attenuated additional 12 dB (effect of antenna pattern, delays remain the same). The simulation results for all the six channels arc e\ aluated. The above experiments are done using the simulation in Matlab communication tool box. IV. The output for the perfc MATLAB coding with BPSK modulati SIMULATION RESULTS of mobile WiMAX was estimated by the BER and the SNR plot t The bandwidth used in the experiment was 3.5 MHz Bit Error Rate Of Mobile Wima.x (Phy) Under Different Communication... Figure3.BER curve for BPSK modulation The output for the performance of mobile WiMAX was estimated by the Bit Error Rate and the Signal to Noise Ratio plot using the MATLAB coding with Quadrature Phase Shift Keying modulation technique is given below in figure 4. BER of the received symbols. ( G=0.25.BW=3.5MHz and modulation of QPSK ) Figure 4. BER curve for QPSK modulation The output for the performance of mobile WiMAX was estimated by the BER and the SNR plot using the MATLAB coding with 16QAM modulation. It is illustrated in the figure5. Figure5. BER curve for 16QAM modulation Bit Error Rate Of Mobile Wimax (Phy) Under Different Communication... The output for the performance of mobile Wimax was estimated by the BER and the SNR plot using the MATLAB coding with 64QAM modulation and graphical illustration done as in figure 6. Figure6. BER curve for 64QAM modulation V. CONCLUSION In this paper, the performance of mobile WIMAX physical layer for OFDMA on different channel condition assisted by Mobile IP(Internet protocol) for mobility management was analyzed. The analysis demonstrated that the modulation and coding rate had a greater impact on the relative performance between the different SU1 channel conditions. The performance was analyzed under SUI channel models with different modulation techniques for mobility management. It is found from the performance graphs that SUI channel 5 and 6 performs better than the conventional ones. REFERENCES IEEE 2010 Omar Arafat,K.Dimyati, a study of physical layer of Mobile WiMax under different communication channels & modulation technique. [2JIEEE std 802.16 Etm-2004"Part 16: Air Interface for fixed and mobile broadband wireless Access system,"Feb 2004. Md.ZahidHasan.Mu.A .hiaiiillslam, Comparative Study of Different Guard Time Intervals to Improve the BER Performance of WiM AX Systems to Minimize the Effects of ISI and 1CI under Adaptive Modulation Techniques over SUI-1 and AWGN Communication Channels, (IICSIS) International Journal of Computer Science and Information Security, Vol. 6, No.2, 2009. IEEE 802.16 Broadband Wireless Access Working Group Simulating the SUI Channel Models Li-Chun Wang Department of Communications Engineering National Chiao Tung University Hsinchu,Taiwan. Mai Tran, G Zaggaoulos and A .Nix" Mobile WiMAX MIMO performance Analysis: Downlink and Uplink", PIMRC2008. J.GAndews, A.Ghoshand R.Muhamed, Fundamentals of WiMAX Understanding broadband Wireless Networks, "Prentice Hall, Feb 2007. RajJain,@aum.org,"ChannelModelaTutorial", feb21,2007 submitted to wimax forum at aum. M.S. Smith and C. Tappenden, 'Additional enhancements to interim channel models for G2 MMDS fixed wireless applications," IEEE 802.16.3c-00/53 M.S.Smith, J.E.J. Dalley, "A new methodology for deriving path loss models from cellular drive test data", Proc.AP2000 Conference, Davos, Switzerland, April 2000. V. Erceget.al, "A model for the multipath delay profile of fixed wireless channels," IEEE JSAC, vol. 17, no. 3, March 1999, pp. 399-410. L.J.Greenstein, V. Erceg, Y.S. Yeh, and M.V. Clark, "A new path-gain/delay-spread propagation model for digital cellular channels," IEEE Trans. Veh. Technol., vol. 46, no. 2, May 1997. J.W. Porter and J.A. Thweatt, "Microwave propagation characteristics in the MMDS frequency band," ICC'2000 Conference Proceedings, pp. 1578-1582. L.J. Greenstein, S. Ghassemzadeh, V.Erceg, and DG. Michelson, "Ricean K-factors in narrowband fixed wireless channels: Theory, experiments, and statistical models," WPMC'99 Conference Proceedings, Amsterdam, September 1999.

Use only the information given below. Keep your responses concise and use bullet points where appropriate.

If I'm looking to minimise my tax exposure for my retirement funds, what are some things I should focus on?

So, how do you actually implement the investment plan outlined above? As mentioned in the first section, your biggest priority is to get yourself out of debt; until that point, the only investing you should be doing is with the minimum 401(k) or other defined contribution savings required to “max out” your employer match; beyond that, you should earmark every spare penny to eliminating your student and consumer debt. Next, you’ll need an emergency fund placed in T-bills, CDs, or money market accounts; this should be enough for six months of living expenses, and should be in a taxable account. (Putting your emergency money in a 401(k) or IRA is a terrible idea, since if you need it, you’ll almost certainly have to pay a substantial tax penalty to get it out.) Then, and only then, can you start to save seriously for retirement. For most young people, this will mean some mix of an employer-based plan, such as a 401(k), individual IRA accounts, and taxable accounts. There are two kinds of IRA accounts: traditional and Roth. The main difference between the two comes when you pay taxes on them; with a traditional account, you get a tax deduction on the contributions, and pay taxes when the money is withdrawn, generally after age 59½. (You can withdraw money before 59½, but, with a few important exceptions, you’ll pay a substantial tax penalty for doing so.) With a Roth, it’s the opposite: you contribute with money you’ve already paid taxes on, but pay no taxes on withdrawals in retirement. There’s thus not a lot of difference between a 401(k) and a traditional IRA; in fact, you can seamlessly roll the former into the latter after you leave your employer. In general, the Roth is a better deal than a traditional IRA, since not only can you contribute “more” to the Roth (since $5,500—the current annual contribution limit—of after-tax dollars is worth a lot more than $5,500 in pre-tax dollars), but also you’re hopefully in a higher tax bracket when you retire. Your goal, as mentioned, is to save at least 15 percent of your salary in some combination of 401(k)/IRA/taxable savings. But in reality, the best strategy is to save as much as you can, and don’t stop doing so until the day you die. The optimal strategy for most young people is thus to first max out their 401(k) match, then contribute the maximum to a Roth IRA (assuming they’re not making too much money to qualify for the Roth, approximately $200,000 for a married couple and $120,000 for a single person), then save in a taxable account on top of that. A frequent problem with 401(k) plans is the quality of the fund offerings. You should look carefully at the fund expenses offered in your employer’s plan. If its expense ratios are in general more than 1.0%, then you have a lousy one, and you should contribute only up to the match. If its expenses are in general lower than 0.5%, and particularly if it includes Vanguard’s index funds or Fidelity’s Spartanclass funds (which have fees as low as Vanguard’s), then you might consider making significant voluntary contributions in excess of the match limits. For most young savers, fully maxing out voluntary 401(k) contributions (assuming you have a “good” 401(k) with low expenses) and the annual Roth limit will get them well over the 15 percent savings target. Your contributions to your 401(k), IRA, and taxable accounts should be made equally to the indexed U.S. stock, foreign stock, and bond funds available to you. Once per year, you should “rebalance” them back to equal status. In the good years, this will mean selling some stocks, which you should avoid doing in a taxable account, since this will incur capital gains taxes. In practice, this means keeping a fair amount of your stock holdings in a tax sheltered 401(k) or IRA. This will not be a problem for the typical young investor, since he or she will have a relatively small amount of his or her assets in a taxable account.

If I'm looking to minimise my tax exposure for my retirement funds, what are some things I should focus on? Use only the information given below. Keep your responses concise and use bullet points where appropriate. So, how do you actually implement the investment plan outlined above? As mentioned in the first section, your biggest priority is to get yourself out of debt; until that point, the only investing you should be doing is with the minimum 401(k) or other defined contribution savings required to “max out” your employer match; beyond that, you should earmark every spare penny to eliminating your student and consumer debt. Next, you’ll need an emergency fund placed in T-bills, CDs, or money market accounts; this should be enough for six months of living expenses, and should be in a taxable account. (Putting your emergency money in a 401(k) or IRA is a terrible idea, since if you need it, you’ll almost certainly have to pay a substantial tax penalty to get it out.) Then, and only then, can you start to save seriously for retirement. For most young people, this will mean some mix of an employer-based plan, such as a 401(k), individual IRA accounts, and taxable accounts. There are two kinds of IRA accounts: traditional and Roth. The main difference between the two comes when you pay taxes on them; with a traditional account, you get a tax deduction on the contributions, and pay taxes when the money is withdrawn, generally after age 59½. (You can withdraw money before 59½, but, with a few important exceptions, you’ll pay a substantial tax penalty for doing so.) With a Roth, it’s the opposite: you contribute with money you’ve already paid taxes on, but pay no taxes on withdrawals in retirement. There’s thus not a lot of difference between a 401(k) and a traditional IRA; in fact, you can seamlessly roll the former into the latter after you leave your employer. In general, the Roth is a better deal than a traditional IRA, since not only can you contribute “more” to the Roth (since $5,500—the current annual contribution limit—of after-tax dollars is worth a lot more than $5,500 in pre-tax dollars), but also you’re hopefully in a higher tax bracket when you retire. Your goal, as mentioned, is to save at least 15 percent of your salary in some combination of 401(k)/IRA/taxable savings. But in reality, the best strategy is to save as much as you can, and don’t stop doing so until the day you die. The optimal strategy for most young people is thus to first max out their 401(k) match, then contribute the maximum to a Roth IRA (assuming they’re not making too much money to qualify for the Roth, approximately $200,000 for a married couple and $120,000 for a single person), then save in a taxable account on top of that. A frequent problem with 401(k) plans is the quality of the fund offerings. You should look carefully at the fund expenses offered in your employer’s plan. If its expense ratios are in general more than 1.0%, then you have a lousy one, and you should contribute only up to the match. If its expenses are in general lower than 0.5%, and particularly if it includes Vanguard’s index funds or Fidelity’s Spartanclass funds (which have fees as low as Vanguard’s), then you might consider making significant voluntary contributions in excess of the match limits. For most young savers, fully maxing out voluntary 401(k) contributions (assuming you have a “good” 401(k) with low expenses) and the annual Roth limit will get them well over the 15 percent savings target. Your contributions to your 401(k), IRA, and taxable accounts should be made equally to the indexed U.S. stock, foreign stock, and bond funds available to you. Once per year, you should “rebalance” them back to equal status. In the good years, this will mean selling some stocks, which you should avoid doing in a taxable account, since this will incur capital gains taxes. In practice, this means keeping a fair amount of your stock holdings in a tax sheltered 401(k) or IRA. This will not be a problem for the typical young investor, since he or she will have a relatively small amount of his or her assets in a taxable account.

Present the answers in a table with bullet points. Only use the information provided.

Summarise the different nanoparticles by giving 3 benefits of each and any indication of the type of diabetes they best treat.

3.1. Using nanotechnology to treat diabetes mellitus Recent advances in diabetes research have been leveraged by nanotechnology to develop cutting-edge glucose measurement and insulin delivery techniques with the potential to significantly enhance the well-being of diabetes patients. This analysis delves into the intersection of nanotechnology and diabetes research, specifically focusing on the developmental of glucose sensors utilizing nanoscale elements like metal nanoparticles and carbon nanostructures. These tiny components have been proven to enhance the sensitivity and response time of glucose sensors, enabling continuous monitoring of glucose levels within the body. Additionally, the review delves into the nanoscale strategies for creating “closed-loop” insulin delivery systems that automatically adjust insulin release based on blood glucose changes. By integrating blood glucose measurements with insulin administration, these systems aim to reduce the need for patient intervention, ultimately leading to improved health outcomes and overall quality of life for individuals with diabetes mellitus [17]. 3.2. The use of nanoparticles in biology for treating diabetes mellitus Nanotechnology has emerged as a valuable tool for a range of biomedical uses in recent years. Nanoparticles, which are materials with sizes smaller than 100 nm in at least one dimension, have distinct characteristics that change when scaled down to the nanoscale. This enables them to interact with cellular biomolecules in a specific manner. NPs engineered for precise cell delivery carry therapeutic substances [18]. Moreover, metal nanoparticles are perceived as being less harmful than mineral salts and provide numerous advantages to the body [19]. 3.2.1. Zinc oxide NPs ZnO nanoparticles (NPs) find uses in a range of biomedical applications, including treating diabetes, fighting bacteria, combating cancer and fungal infections, delivering drugs, and reducing inflammation [20]. Zinc is crucial for the biosynthesis, secretion, and storage of insulin, with zinc transporters like zinc transporter-8 being vital for insulin release from pancreatic beta cells [21]. ZnO NPs can boost insulin signaling by enhancing insulin receptor phosphorylation and phosphoinositide 3-kinase activity [22]. Research indicates that ZnO NPs can repair pancreatic tissue damaged by diabetes, improving blood sugar and serum insulin levels. Studies comparing ZnO NPs with standard antidiabetic drugs like Vildagliptin show that ZnO NPs are effective in treating type 2 diabetes [23]. ZnO NPs have shown notable antidiabetic activity in various animal models, often surpassing other treatments. They also have powerful biological effects, such as acting as antioxidants and reducing inflammation, which makes them potential candidates for treating diabetes and its related complications [24]. 3.2.2. Magnesium NPs Magnesium (Mg) is essential for glucose homeostasis and insulin secretion, Contribution to the process of adding phosphate groups to molecules and regulating the breakdown of glucose through a variety of enzymes [19]. Mg deficiency can result in insulin resistance, dyslipidemia, and complications in diabetic mice [25]. A study by Kei et al. (2020) demonstrated that MgO nanoparticles can help reduce blood sugar levels, improve insulin sensitivity, and regulate lipid levels in diabetic mice. The study found that using the polymer-directed aptamer (DPAP) system efficiently delivered MgO NPs to diabetic target cells, leading to reduced sugar oxidation. This suggests that magnesium, particularly in the form of MgO NPs, may be a promising treatment for type II diabetes [26]. 3.2.3. Cerium oxide NPs The rare earth element cerium, found in the lanthanide series, forms CeO2 nanoparticles (NPs) that have shown potential in treating oxidative disorders and brain injuries. Research indicates that CeO2 NPs could serve as a regenerative agent, preventing nerve damage caused by diabetes and treating diabetic neuropathy [27]. Additionally, CeO2 NPs may help reduce complications from gestational diabetes. However, further research is needed to validate these findings [28]. 3.2.4. Copper NPs Copper is a crucial transitional element involved in various biochemical processes. Copper nanoparticles (Cu NPs) are effective in treating Type 2 diabetes due to their superior antioxidant properties and their ability to inhibit alphaamylase and alpha-glucosidase [29]. Additionally, Cu NPs have been shown to significantly prevent cardiovascular defects in diabetic individuals by enhancing nitric oxide availability in the vascular endothelium and reducing oxidative stress. Research indicates that Cu NPs also aid in wound healing in diabetic mice, accelerating recovery and controlling bacterial infections. Overall, Cu NPs show potential benefits for diabetes patients [30]. 3.2.5. Selenium NPs Selenium is a vital trace element found in many plants, and its deficit can result in health issues like diabetes [31]. Selenium nanoparticles (Se NPs) are less toxic and have antioxidant properties that help scavenge peroxides and protect cellular macromolecules. Studies indicate that Se NPs can assist in managing T2DM by preserving the authenticity of pancreatic β-cells, boosting insulin secretion, and reducing glucose levels. Additionally, they enhance liver function and lower inflammatory markers. Overall, Se NPs hold promise as a treatment for diabetes and insulin resistance, effectively mitigating related complications while maintaining a balance between oxidative and antioxidant processes [32].

Summarise the different nanoparticles by giving 3 benefits of each and any indication of the type of diabetes they best treat. Present the answers in a table with bullet points. Only use the information provided. 3.1. Using nanotechnology to treat diabetes mellitus Recent advances in diabetes research have been leveraged by nanotechnology to develop cutting-edge glucose measurement and insulin delivery techniques with the potential to significantly enhance the well-being of diabetes patients. This analysis delves into the intersection of nanotechnology and diabetes research, specifically focusing on the developmental of glucose sensors utilizing nanoscale elements like metal nanoparticles and carbon nanostructures. These tiny components have been proven to enhance the sensitivity and response time of glucose sensors, enabling continuous monitoring of glucose levels within the body. Additionally, the review delves into the nanoscale strategies for creating “closed-loop” insulin delivery systems that automatically adjust insulin release based on blood glucose changes. By integrating blood glucose measurements with insulin administration, these systems aim to reduce the need for patient intervention, ultimately leading to improved health outcomes and overall quality of life for individuals with diabetes mellitus [17]. 3.2. The use of nanoparticles in biology for treating diabetes mellitus Nanotechnology has emerged as a valuable tool for a range of biomedical uses in recent years. Nanoparticles, which are materials with sizes smaller than 100 nm in at least one dimension, have distinct characteristics that change when scaled down to the nanoscale. This enables them to interact with cellular biomolecules in a specific manner. NPs engineered for precise cell delivery carry therapeutic substances [18]. Moreover, metal nanoparticles are perceived as being less harmful than mineral salts and provide numerous advantages to the body [19]. 3.2.1. Zinc oxide NPs ZnO nanoparticles (NPs) find uses in a range of biomedical applications, including treating diabetes, fighting bacteria, combating cancer and fungal infections, delivering drugs, and reducing inflammation [20]. Zinc is crucial for the biosynthesis, secretion, and storage of insulin, with zinc transporters like zinc transporter-8 being vital for insulin release from pancreatic beta cells [21]. ZnO NPs can boost insulin signaling by enhancing insulin receptor phosphorylation and phosphoinositide 3-kinase activity [22]. Research indicates that ZnO NPs can repair pancreatic tissue damaged by diabetes, improving blood sugar and serum insulin levels. Studies comparing ZnO NPs with standard antidiabetic drugs like Vildagliptin show that ZnO NPs are effective in treating type 2 diabetes [23]. ZnO NPs have shown notable antidiabetic activity in various animal models, often surpassing other treatments. They also have powerful biological effects, such as acting as antioxidants and reducing inflammation, which makes them potential candidates for treating diabetes and its related complications [24]. 3.2.2. Magnesium NPs Magnesium (Mg) is essential for glucose homeostasis and insulin secretion, Contribution to the process of adding phosphate groups to molecules and regulating the breakdown of glucose through a variety of enzymes [19]. Mg deficiency can result in insulin resistance, dyslipidemia, and complications in diabetic mice [25]. A study by Kei et al. (2020) demonstrated that MgO nanoparticles can help reduce blood sugar levels, improve insulin sensitivity, and regulate lipid levels in diabetic mice. The study found that using the polymer-directed aptamer (DPAP) system efficiently delivered MgO NPs to diabetic target cells, leading to reduced sugar oxidation. This suggests that magnesium, particularly in the form of MgO NPs, may be a promising treatment for type II diabetes [26]. 3.2.3. Cerium oxide NPs The rare earth element cerium, found in the lanthanide series, forms CeO2 nanoparticles (NPs) that have shown potential in treating oxidative disorders and brain injuries. Research indicates that CeO2 NPs could serve as a regenerative agent, preventing nerve damage caused by diabetes and treating diabetic neuropathy [27]. Additionally, CeO2 NPs may help reduce complications from gestational diabetes. However, further research is needed to validate these findings [28]. 3.2.4. Copper NPs Copper is a crucial transitional element involved in various biochemical processes. Copper nanoparticles (Cu NPs) are effective in treating Type 2 diabetes due to their superior antioxidant properties and their ability to inhibit alphaamylase and alpha-glucosidase [29]. Additionally, Cu NPs have been shown to significantly prevent cardiovascular defects in diabetic individuals by enhancing nitric oxide availability in the vascular endothelium and reducing oxidative stress. Research indicates that Cu NPs also aid in wound healing in diabetic mice, accelerating recovery and controlling bacterial infections. Overall, Cu NPs show potential benefits for diabetes patients [30]. 3.2.5. Selenium NPs Selenium is a vital trace element found in many plants, and its deficit can result in health issues like diabetes [31]. Selenium nanoparticles (Se NPs) are less toxic and have antioxidant properties that help scavenge peroxides and protect cellular macromolecules. Studies indicate that Se NPs can assist in managing T2DM by preserving the authenticity of pancreatic β-cells, boosting insulin secretion, and reducing glucose levels. Additionally, they enhance liver function and lower inflammatory markers. Overall, Se NPs hold promise as a treatment for diabetes and insulin resistance, effectively mitigating related complications while maintaining a balance between oxidative and antioxidant processes [32].

Use only the information provided to you to generate an answer. Never rely on external sources or internal knowledge to answer questions. Provide your answer in a bulleted list, and use sub-bullets for organization of additional information if necessary.

Who has the authority to change the schedule class of marijuana?

Either Congress or the executive branch has the authority to change the status of marijuana under the CSA. Congress can change the status of a controlled substance through legislation, while the CSA empowers DEA to make scheduling decisions through the notice-and-comment rulemaking process. When considering whether to schedule or reschedule a controlled substance, DEA is bound by HHS’s recommendations on scientific and medical matters. However, DEA has stated that it has “final authority to schedule, reschedule, or deschedule a drug under the Controlled Substances Act.” A proposal from the 118th Congress would provide for congressional review of DEA rescheduling decisions related to marijuana. If Congress wishes to change the legal status of marijuana, it has broad authority to do so before or after DEA makes any final scheduling decision. Several proposals from the 118th Congress would remove marijuana from control under the CSA or move the substance to a less restrictive schedule. If Congress moved marijuana to Schedule III by legislation, it could simultaneously consider whether to change some of the legal consequences of Schedule III status described above. Congress could also legislate to move marijuana to another CSA schedule, which would subject it to controls more or less stringent than those that apply to Schedule III controlled substances.

Use only the information provided to you to generate an answer. Never rely on external sources or internal knowledge to answer questions. Provide your answer in a bulleted list, and use sub-bullets for organization of additional information if necessary. Question: Who has the authority to change the schedule class of marijuana? Context: Either Congress or the executive branch has the authority to change the status of marijuana under the CSA. Congress can change the status of a controlled substance through legislation, while the CSA empowers DEA to make scheduling decisions through the notice-and-comment rulemaking process. When considering whether to schedule or reschedule a controlled substance, DEA is bound by HHS’s recommendations on scientific and medical matters. However, DEA has stated that it has “final authority to schedule, reschedule, or deschedule a drug under the Controlled Substances Act.” A proposal from the 118th Congress would provide for congressional review of DEA rescheduling decisions related to marijuana. If Congress wishes to change the legal status of marijuana, it has broad authority to do so before or after DEA makes any final scheduling decision. Several proposals from the 118th Congress would remove marijuana from control under the CSA or move the substance to a less restrictive schedule. If Congress moved marijuana to Schedule III by legislation, it could simultaneously consider whether to change some of the legal consequences of Schedule III status described above. Congress could also legislate to move marijuana to another CSA schedule, which would subject it to controls more or less stringent than those that apply to Schedule III controlled substances.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

I moved to an apartment in a duplex building two months ago. My landlord lives in the other apartment in the same building. I am an adept of Santería, and, after a small ceremony in my living room using incense, I received a notice from my landlord. He asked me to leave the premises because the contract stipulates that only Protestants might rent his apartments and that utilization of incense is prohibited. The contract contains this provision indeed, but I can't accept it! That's open discrimination! My state follows the FHA's broad dispositions. Who will prevail?

A Guide To The Fair Housing Act And Its Exemptions Everyone deserves a stable, affordable place to live. But the unfortunate truth is that discrimination in housing has prevented some vulnerable groups from achieving this cornerstone of the American Dream. The good news is that there are laws in place to protect people from being discriminated against when securing housing. One of the most important is the Fair Housing Act (FHA). Here’s what the FHA covers and how you can protect yourself from discriminatory practices. Faster, easier mortgage lending Check your rates today with Better Mortgage. View Rates What Is the Fair Housing Act of 1968? The Fair Housing Act is a critical set of guidelines that prevent prospective homeowners and renters from discrimination through the sale, rental agreement or financing of their home. The act was signed into law by President Lydon Johnson in 1968 after several years of policymakers struggling to push it through until the assassination of Rev. Dr. Martin Luther King, Jr. prompted congressional action. Today, the U.S. Department of Housing and Urban Development (HUD) oversees and enforces the Fair Housing Act. It prohibits discrimination in housing based on: race or color, national origin, religion, sex (including sexual orientation and gender identity, per a new executive order), familial status and disabilty. Anyone who attempts to rent, buy or sell a home, take out a mortgage or obtain housing assistance, is protected. The act also applies to most housing types, with a few exceptions. How the Fair Housing Act Protects Against Housing Discrimination Housing is a broad term. So who, exactly, is prohibited from engaging in discrimination? The FHA outlaws discrimination by: Landlords Property owners and managers Developers Real estate agents Mortgage lenders and brokers Homeowner associations Insurance providers Anyone else who impacts housing opportunities Essentially, any person or entity that’s involved in the process of securing housing is required to follow FHA guidelines. If someone believes they were discriminated against, they can contact HUD, which they will then investigate. Examples of Housing Discrimination Discrimination can occur in many ways and to different classes of people. Here are a few examples: Selling or renting. It’s illegal to refuse a home sale or rental to someone based on race, sex or any of the other factors outlined in the FHA. That includes falsely stating that a home is no longer on the market when it is, or providing different terms or facilities to one person over another. It’s also against the law to persuade homeowners to sell or rent their property based on the fact that people of a particular race or other protected class are moving into the neighborhood, intending to earn a profit. Mortgage lending. Lenders can also discriminate against mortgage applicants if the lender refuses to provide information about a loan, rejected the applicant entirely or imposed different terms and conditions (interest rates, fees, etc.) based on the applicant’s race, color, religion, sex, disability, familial status or national origin. Similar discrimination can occur during the appraisal process. Homeowners insurance. If an insurance company refuses to provide homeowners insurance to an owner or occupant of a dwelling because of their race, color, religion, sex, disability, familial status or national origin, it’s considered discrimination. It’s also discrimination to offer different terms or conditions, or provide limited or information about an insurance product based on those same factors. Accommodating disabilities. People who have mental or physical disabilities (such as mobility impairment or chronic mental illness) that “substantially limits one or more major life activities” are entitled to certain housing accommodations. If reasonable accommodations aren’t allowed even at your own expense, it may be considered discrimination. For example, a building that usually doesn’t permit tenants to have pets would need to allow a visually impaired tenant to keep a guide animal. Advertising. When advertising the sale or rental availability of a dwelling, any language published that indicates preference or limitations based on race, color, religion, sex, disability, familial status or national origin is discrimination. This also applies to advertising for single-family and owner-occupied housing, which is otherwise exempt from the FHA. Fair Housing Act Exemptions Though the Fair Housing Act applies to most situations, there are some exemptions. For example, if a dwelling has four or fewer units and the owner lives in one of them, they are exempt from the FHA. However, they would not be exempt under the Pennsylvania Human Relations Act unless the dwelling contained only two units and one was owner-occupied. Additionally, any single-family housing that’s sold or rented without the use of a broker is exempt from the FHA, as long as the owner is a private individual who doesn’t own more than three such homes at one time. Again, they would not be exempt in the state of Pennsylvania due to the Pennsylvania Human Relations Act. Housing communities for the elderly are also exempt from the FHA in most cases. In order to not violate the family status provision, it must meet one of several conditions. For instance, HUD must have determined that it’s specifically designed for and occupied by elderly occupants under a federal, state or local government program. Alternatively, it can be 100% occupied by people age 62 or older. Another option is that the community houses at least one person age 55 or older in at least 80% of the occupied units. The property must also have a policy demonstrating that the intent of the community is to house people age 55 or older. Finally, religious organizations and private clubs are allowed to give preference to members as long as they don’t discriminate in their membership. How Fair Housing Laws Are Enforced The HUD is the federal agency in charge of implementing and enforcing the Fair Housing Act. It does so through its Office of Fair Housing and Equal Opportunity (FHEO), which is headquartered in Washington, with 10 regional offices across the U.S. The purpose of these offices is to enforce FHA compliance, administer fair housing programs and educate consumers. The FHEO primarily enforces fair housing programs by funding third-party organizations. For instance, the Fair Housing Initiatives Program provides grants to private organizations that investigate complaints, and even place people undercover to find FHA violations. How to Protect Yourself Against Fair Housing Violations If you believe your rights were violated under the Fair Housing Act, it’s important to file a complaint right away. HUD will investigate claims made within one year of the violation. When filing a complaint, be prepared to provide the following information: Your name and address Name and address of the person or company your complaint is against (also known as the respondent) Address or other identification of the housing involved The date and a brief description of the incident that led to your rights being violated You can file a complaint with the FHEO online, using the HUD Form 903. You can also download this form and email it to your local FHEO office. You can also mail a letter or call an office directly. Once your complaint is received and accepted, HUD will notify you in writing. It will also notify the respondent that you filed a complaint and give them some time to submit a written response. The FHEO will investigate your complaint and decide whether or not there is reasonable cause to believe that the respondent violated the FHA. Additionally, HUD will offer you and the respondent the opportunity to voluntarily resolve the complaint with a Conciliation Agreement. If it’s determined there was a rights violation and you don’t come to an agreement with the respondent, you may need to consult with a lawyer and determine the next steps.

"================ <TEXT PASSAGE> ======= A Guide To The Fair Housing Act And Its Exemptions Everyone deserves a stable, affordable place to live. But the unfortunate truth is that discrimination in housing has prevented some vulnerable groups from achieving this cornerstone of the American Dream. The good news is that there are laws in place to protect people from being discriminated against when securing housing. One of the most important is the Fair Housing Act (FHA). Here’s what the FHA covers and how you can protect yourself from discriminatory practices. Faster, easier mortgage lending Check your rates today with Better Mortgage. View Rates What Is the Fair Housing Act of 1968? The Fair Housing Act is a critical set of guidelines that prevent prospective homeowners and renters from discrimination through the sale, rental agreement or financing of their home. The act was signed into law by President Lydon Johnson in 1968 after several years of policymakers struggling to push it through until the assassination of Rev. Dr. Martin Luther King, Jr. prompted congressional action. Today, the U.S. Department of Housing and Urban Development (HUD) oversees and enforces the Fair Housing Act. It prohibits discrimination in housing based on: race or color, national origin, religion, sex (including sexual orientation and gender identity, per a new executive order), familial status and disabilty. Anyone who attempts to rent, buy or sell a home, take out a mortgage or obtain housing assistance, is protected. The act also applies to most housing types, with a few exceptions. How the Fair Housing Act Protects Against Housing Discrimination Housing is a broad term. So who, exactly, is prohibited from engaging in discrimination? The FHA outlaws discrimination by: Landlords Property owners and managers Developers Real estate agents Mortgage lenders and brokers Homeowner associations Insurance providers Anyone else who impacts housing opportunities Essentially, any person or entity that’s involved in the process of securing housing is required to follow FHA guidelines. If someone believes they were discriminated against, they can contact HUD, which they will then investigate. Examples of Housing Discrimination Discrimination can occur in many ways and to different classes of people. Here are a few examples: Selling or renting. It’s illegal to refuse a home sale or rental to someone based on race, sex or any of the other factors outlined in the FHA. That includes falsely stating that a home is no longer on the market when it is, or providing different terms or facilities to one person over another. It’s also against the law to persuade homeowners to sell or rent their property based on the fact that people of a particular race or other protected class are moving into the neighborhood, intending to earn a profit. Mortgage lending. Lenders can also discriminate against mortgage applicants if the lender refuses to provide information about a loan, rejected the applicant entirely or imposed different terms and conditions (interest rates, fees, etc.) based on the applicant’s race, color, religion, sex, disability, familial status or national origin. Similar discrimination can occur during the appraisal process. Homeowners insurance. If an insurance company refuses to provide homeowners insurance to an owner or occupant of a dwelling because of their race, color, religion, sex, disability, familial status or national origin, it’s considered discrimination. It’s also discrimination to offer different terms or conditions, or provide limited or information about an insurance product based on those same factors. Accommodating disabilities. People who have mental or physical disabilities (such as mobility impairment or chronic mental illness) that “substantially limits one or more major life activities” are entitled to certain housing accommodations. If reasonable accommodations aren’t allowed even at your own expense, it may be considered discrimination. For example, a building that usually doesn’t permit tenants to have pets would need to allow a visually impaired tenant to keep a guide animal. Advertising. When advertising the sale or rental availability of a dwelling, any language published that indicates preference or limitations based on race, color, religion, sex, disability, familial status or national origin is discrimination. This also applies to advertising for single-family and owner-occupied housing, which is otherwise exempt from the FHA. Fair Housing Act Exemptions Though the Fair Housing Act applies to most situations, there are some exemptions. For example, if a dwelling has four or fewer units and the owner lives in one of them, they are exempt from the FHA. However, they would not be exempt under the Pennsylvania Human Relations Act unless the dwelling contained only two units and one was owner-occupied. Additionally, any single-family housing that’s sold or rented without the use of a broker is exempt from the FHA, as long as the owner is a private individual who doesn’t own more than three such homes at one time. Again, they would not be exempt in the state of Pennsylvania due to the Pennsylvania Human Relations Act. Housing communities for the elderly are also exempt from the FHA in most cases. In order to not violate the family status provision, it must meet one of several conditions. For instance, HUD must have determined that it’s specifically designed for and occupied by elderly occupants under a federal, state or local government program. Alternatively, it can be 100% occupied by people age 62 or older. Another option is that the community houses at least one person age 55 or older in at least 80% of the occupied units. The property must also have a policy demonstrating that the intent of the community is to house people age 55 or older. Finally, religious organizations and private clubs are allowed to give preference to members as long as they don’t discriminate in their membership. How Fair Housing Laws Are Enforced The HUD is the federal agency in charge of implementing and enforcing the Fair Housing Act. It does so through its Office of Fair Housing and Equal Opportunity (FHEO), which is headquartered in Washington, with 10 regional offices across the U.S. The purpose of these offices is to enforce FHA compliance, administer fair housing programs and educate consumers. The FHEO primarily enforces fair housing programs by funding third-party organizations. For instance, the Fair Housing Initiatives Program provides grants to private organizations that investigate complaints, and even place people undercover to find FHA violations. How to Protect Yourself Against Fair Housing Violations If you believe your rights were violated under the Fair Housing Act, it’s important to file a complaint right away. HUD will investigate claims made within one year of the violation. When filing a complaint, be prepared to provide the following information: Your name and address Name and address of the person or company your complaint is against (also known as the respondent) Address or other identification of the housing involved The date and a brief description of the incident that led to your rights being violated You can file a complaint with the FHEO online, using the HUD Form 903. You can also download this form and email it to your local FHEO office. You can also mail a letter or call an office directly. Once your complaint is received and accepted, HUD will notify you in writing. It will also notify the respondent that you filed a complaint and give them some time to submit a written response. The FHEO will investigate your complaint and decide whether or not there is reasonable cause to believe that the respondent violated the FHA. Additionally, HUD will offer you and the respondent the opportunity to voluntarily resolve the complaint with a Conciliation Agreement. If it’s determined there was a rights violation and you don’t come to an agreement with the respondent, you may need to consult with a lawyer and determine the next steps. https://www.forbes.com/advisor/mortgages/fair-housing-act/ ================ <QUESTION> ======= I moved to an apartment in a duplex building two months ago. My landlord lives in the other apartment in the same building. I am an adept of Santería, and, after a small ceremony in my living room using incense, I received a notice from my landlord. He asked me to leave the premises because the contract stipulates that only Protestants might rent his apartments and that utilization of incense is prohibited. The contract contains this provision indeed, but I can't accept it! That's open discrimination! My state follows the FHA's broad dispositions. Who will prevail? ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Only provide the opinions that were given in the context document. If you cannot answer a question using the provided context alone, then say "I'm sorry, but I do not have the context to answer this question."

Using a Chromebook, how do I locate the text app?

Skip to content Tech Time With Timmy logo Home Videos Articles About Us Contact Us SearchSearch Search... How To Create A Text File On A Chromebook August 9, 2022 This Article May Contain Affiliate Links how to create a text file on chromebook Table of Contents How To Create A TXT file On A Chromebook How To Save The TXT File How To Open The TXT File Text files (or .txt files) are useful files that contain plain, unformatted text. And if you ever want to create a new .txt file on your Chromebook, you’re in luck. Because that’s exactly what I’m going to show you how to do in this article. Prefer to watch a video about how to create a text file on a Chromebook? Click here. Before we begin, I’d just like to point out that a .txt file is a very basic file that contains only unformatted plain text. And if you want to create a file with nicer looking formatted text on a Chromebook, I would recommend something like Google Docs. But if you do want to create a .txt file, let’s proceed with the tutorial. How To Create A TXT file On A Chromebook Chrome OS comes with a built in app for creating, saving, opening, and editing .txt files. So to create a text on your Chromebook, you’ll just need to open an app called “Text” which should already be preinstalled on your Chromebook. So just click on the circle in the bottom left hand corner to view all your apps… txt chromebook And you should find the “Text” app somewhere in here. how to create a text file on a chromebook Now you’ll be in the “Text” app, and if you’ve never used the text app before, it will automatically create a new .txt file for you, and you’ll be ready to start typing! how to create a txt file on a chromebook However, if you’ve opened a different .txt file on your Chromebook in the past, it would have opened in the Text app, and now whenever you open the Text app you’ll just be looking at that old file. how to create a txt file on chromebook But don’t worry, if this happens, just click “New” at the top of the left hand menu and it will create a new blank .txt file just like it would if you opened the app for the first time. how to create text file on chromebook But once you’ve got a blank text file like this, you’re ready to type whatever you want in it. how to create txt file on chromebook How To Save The TXT File Once you’ve typed your text into your new text file, all that’s left to do is save it. In the future, when you’re saving changes to an existing text file, you’ll do that by clicking the “Save” button. But, when you’re saving a brand new text file like this one, you’ll need to click “Save As” instead. how to create text file on a chromebook Now, a files window will appear, and you’ll need to name your .txt file, and choose a location for it. how to create txt file on a chromebook By default, the name of the text file will be whatever you typed in the first line of the file, which in my case is “Hello”. If you’re happy with that name, you don’t have to change it, but if you do want to give the file a propper name, you can do that here. (Just make sure you leave .txt on the end of it so that your computer knows it’s a .txt file). how to make a text file on a chromebook And you can also choose where you want the file to be saved. I’m just going to save mine in the “My files” folder to keep things simple, but if you wanted to save your file in Google Drive, or perhaps in a specific folder inside the “My Files” folder, you could do that now by double clicking the folder you want to save it in. But, once you’re happy with both the file name and the location, you can go ahead and click the “Save” button and your .txt file will be saved! how to make a txt file on a chromebook Now that your .txt file is saved, you can safely close the Text app if you want to. And if you open the files app and open the folder where you saved your .txt file, you will see it somewhere there! how to make text file on chromebook How To Open The TXT File Now that you’ve created your text file, if you want to open it in the future, you’ll just need to find it in the files app in the folder you saved it to, and double click on it… how to make text file on chromebook And the file will open up in the Text app. how to make a txt file on chromebook Just remember, if you make any changes to the file while it’s open, you’ll need to click “Save” before you close the Text app to save the changes. how to make text file on a chromebook And because you clicked the “Save” button instead of “Save As”, you won’t have to choose the name and location or anything, it will just update the existing file with the new changes. And that’s all there is to creating and using text files on a Chromebook! But if you want more Chromebook tutorials, you’ll find them all here. 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Only provide the opinions that were given in the context document. If you cannot answer a question using the provided context alone, then say "I'm sorry, but I do not have the context to answer this question." Using a Chromebook, how do I locate the text app? Skip to content Tech Time With Timmy logo Home Videos Articles About Us Contact Us SearchSearch Search... How To Create A Text File On A Chromebook August 9, 2022 This Article May Contain Affiliate Links how to create a text file on chromebook Table of Contents How To Create A TXT file On A Chromebook How To Save The TXT File How To Open The TXT File Text files (or .txt files) are useful files that contain plain, unformatted text. And if you ever want to create a new .txt file on your Chromebook, you’re in luck. Because that’s exactly what I’m going to show you how to do in this article. Prefer to watch a video about how to create a text file on a Chromebook? Click here. Before we begin, I’d just like to point out that a .txt file is a very basic file that contains only unformatted plain text. And if you want to create a file with nicer looking formatted text on a Chromebook, I would recommend something like Google Docs. But if you do want to create a .txt file, let’s proceed with the tutorial. How To Create A TXT file On A Chromebook Chrome OS comes with a built in app for creating, saving, opening, and editing .txt files. So to create a text on your Chromebook, you’ll just need to open an app called “Text” which should already be preinstalled on your Chromebook. So just click on the circle in the bottom left hand corner to view all your apps… txt chromebook And you should find the “Text” app somewhere in here. how to create a text file on a chromebook Now you’ll be in the “Text” app, and if you’ve never used the text app before, it will automatically create a new .txt file for you, and you’ll be ready to start typing! how to create a txt file on a chromebook However, if you’ve opened a different .txt file on your Chromebook in the past, it would have opened in the Text app, and now whenever you open the Text app you’ll just be looking at that old file. how to create a txt file on chromebook But don’t worry, if this happens, just click “New” at the top of the left hand menu and it will create a new blank .txt file just like it would if you opened the app for the first time. how to create text file on chromebook But once you’ve got a blank text file like this, you’re ready to type whatever you want in it. how to create txt file on chromebook How To Save The TXT File Once you’ve typed your text into your new text file, all that’s left to do is save it. In the future, when you’re saving changes to an existing text file, you’ll do that by clicking the “Save” button. But, when you’re saving a brand new text file like this one, you’ll need to click “Save As” instead. how to create text file on a chromebook Now, a files window will appear, and you’ll need to name your .txt file, and choose a location for it. how to create txt file on a chromebook By default, the name of the text file will be whatever you typed in the first line of the file, which in my case is “Hello”. If you’re happy with that name, you don’t have to change it, but if you do want to give the file a propper name, you can do that here. (Just make sure you leave .txt on the end of it so that your computer knows it’s a .txt file). how to make a text file on a chromebook And you can also choose where you want the file to be saved. I’m just going to save mine in the “My files” folder to keep things simple, but if you wanted to save your file in Google Drive, or perhaps in a specific folder inside the “My Files” folder, you could do that now by double clicking the folder you want to save it in. But, once you’re happy with both the file name and the location, you can go ahead and click the “Save” button and your .txt file will be saved! how to make a txt file on a chromebook Now that your .txt file is saved, you can safely close the Text app if you want to. And if you open the files app and open the folder where you saved your .txt file, you will see it somewhere there! how to make text file on chromebook How To Open The TXT File Now that you’ve created your text file, if you want to open it in the future, you’ll just need to find it in the files app in the folder you saved it to, and double click on it… how to make text file on chromebook And the file will open up in the Text app. how to make a txt file on chromebook Just remember, if you make any changes to the file while it’s open, you’ll need to click “Save” before you close the Text app to save the changes. how to make text file on a chromebook And because you clicked the “Save” button instead of “Save As”, you won’t have to choose the name and location or anything, it will just update the existing file with the new changes. And that’s all there is to creating and using text files on a Chromebook! But if you want more Chromebook tutorials, you’ll find them all here. Prev Previous How To Crop A Picture On A Chromebook Don't Miss an Episode Email Your Email Address Subscribe Leave a Comment Your email address will not be published. Required fields are marked * Type here.. Type here.. Name* Name* Email* Email* Subscribe On Youtube! Subscribe! Popular Posts How To Delete Files On A Chromebook How To Delete Files On A Chromebook If you have files on your Chromebook that you want to delete, you’re in the right place! Because in this article, I’m going to show Read More » How To Open Zip File In Android How To Unzip Files On An Android Phone If you have a zip file on your Android phone that you want to unzip, you’re in the right place. Because in this article, I’m Read More » google photos change date How To Change The Date Of Photos In Google Photos Google Photos is very useful for storing and organizing all your photos. But if some of your photos say they were taken on the wrong Read More » How To Create A Folder On A Chromebook How To Create A Folder On A Chromebook If you want to create a folder on your Chromebook to keep your files organized, you’re in the right place, because today, that’s exactly what Read More » how to change wallpaper on chromebook How To Change Your Wallpaper On A Chromebook If you want to change the wallpaper on your Chromebook to give it a bit of a different look and feel, you’re in the right Read More » How To Delete Files From Google Drive On Android How To Delete Files From Google Drive On Android If you have files on Google Drive that you want to delete using your Android phone, you’re in the right place, because in this article, Read More » how to open rar files on chromebook How To Open RAR Files On A Chromebook RAR files are a type of file similar to zip files that can store multiple files inside them. They’re quite handy for uploading, downloading, and Read More » How To Change All Caps To Lowercase In Google Docs How To Change All Caps To Lowercase In Google Docs We’ve all been there, you type out an entire sentence in Google docs, and then look up at the screen only to discover that caps Read More » how to open rar file in google drive How To Open A Rar File In Google Drive A RAR file is a cool file that can store multiple files inside it. But if you have a RAR file stored in Google Drive, Read More » Categories All Articles Google Docs Tips Google Drive Tutorials Chrome OS Other Tech Tips And Tutorials Latest Videos How To Log Other Devices Out Of Your Google Account How To Log Other Devices Out Of Your Google Account In this video, Timmy shows you how to log other devices out of your Google account. Whether you’ve logged in to your Google account on a borrowed device… Watch Video » How To Use Floating Windows On A Chromebook How To Use Floating Windows On A Chromebook In this video, Timmy shows you how to use a really handy multitasking feature in Chrome OS called Floating Windows. This allows you to have one… Watch Video » How To Transfer Google Drive Files From One Account To Another How To Transfer Google Drive Files From One Account To Another In this video, Timmy shows you how to move files from one Google Drive to another without having to download and re-upload them! If you have files… Watch Video » how to make chromebook sleep How To Make Your Chromebook Sleep In this video, Timmy shows you all four of the different ways to make your Chromebook go to sleep. So whatever your situation, if you want your… Watch Video » How To Close All Tabs In Chrome How To Close All Tabs In Chrome In this video, Timmy shows you how to easily close all of your open tabs in Google Chrome. 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{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== [user request] {passage 0} ========== [context document]

According to this reference text, explain how Vitamin K helps with bone and vascular health, and explain how vitamin K -dependent proteins play a role in vascular health. For brevity, use no more than 200 words.

Vitamin K is best known for promoting proper blood clotting and bone health.1 A meta-analysis of randomized controlled trials revealed that vitamin K supplementation also has favorable effects on glucose metabolism parameters and risk of developing type II diabetes.2 In observational studies, higher intake of vitamin K has been associated with a reduced risk of type II diabetes and improved markers of glucose control.3-5 Clinical trials have shown that vitamin K supplementation can improve metabolic health in adults with diabetes and prediabetes, significantly reducing elevated glucose and insulin levels.6-8 That may help prevent the damage caused by high blood sugar in diabetics and reduce the risk of developing type II diabetes in the first place. The Importance of Vitamin K Vitamin K is found in green leafy vegetables, fermented foods, and some animal products, particularly organ meats. It occurs in two general forms, vitamin K1 and vitamin K2.1 Vitamin K is required for the proper function and activation of different proteins known as vitamin K-dependent proteins. These proteins include several clotting factors that control blood coagulation as well as osteocalcin, a protein tied to vascular and bone health. Some of these vitamin K-dependent proteins help keep calcium in the bones, and out of blood vessels. Calcified blood vessels are one of the hallmarks of atherosclerosis and vascular dysfunction. Without adequate vitamin K, the risk of cardiovascular disease, osteoporosis, and osteopenia rises.1,9 Other vitamin K-dependent proteins have favorable t effects on metabolic function.3,10 Link to Metabolic Health Multiple types of research indicate that Vitamin K2 intake may lower risk of developing type II diabetes.11 The vitamin's role in glucose homeostasis may be due in part to the activation of osteocalcin. In addition to its role in bone mineralization, osteocalcin stimulates healthy insulin and adiponectin expression.12 Studies show that people with higher intake of vitamin K tend to have better insulin sensitivity, better control of blood glucose levels, and a decreased risk of developing type II diabetes.3,5 In an observational study embedded in a randomized controlled trial of the Mediterranean diet for prevention of cardiovascular disease, men and women without cardiovascular disease were followed for 5.5 years. Dietary information was collected annually through questionnaires. It was found that baseline intake of vitamin K1 was lower in participants who developed diabetes during the study. It was also found that the risk of developing diabetes dropped by approximately 17% for every 100 mcg of vitamin K1 consumed per day. Subjects who increased their dietary vitamin K1 intake over those 5.5 years had a 51% reduction in risk for developing diabetes, compared with those who did not increase vitamin K intake. The authors concluded that dietary vitamin K1 is associated with reduced risk of type II diabetes.13 How It Works Vitamin K appears to improve insulin function and glucose metabolism in at least two main ways: Activating vitamin K-dependent proteins is involved in regulating glucose metabolism.3 Suppressing chronic inflammation and production of pro-inflammatory compounds, which is a major contributor to diminished insulin sensitivity and metabolic disease.3 Together, these actions could help reduce elevated glycemic markers and lower risk for diabetic complications.

{instruction} ========== In your answer, refer only to the context document. Do not employ any outside knowledge {question} ========== According to this reference text, explain how Vitamin K helps with bone and vascular health, and explain how vitamin K -dependent proteins play a role in vascular health. For brevity, use no more than 200 words. {passage 0} ========== Vitamin K is best known for promoting proper blood clotting and bone health.1 A meta-analysis of randomized controlled trials revealed that vitamin K supplementation also has favorable effects on glucose metabolism parameters and risk of developing type II diabetes.2 In observational studies, higher intake of vitamin K has been associated with a reduced risk of type II diabetes and improved markers of glucose control.3-5 Clinical trials have shown that vitamin K supplementation can improve metabolic health in adults with diabetes and prediabetes, significantly reducing elevated glucose and insulin levels.6-8 That may help prevent the damage caused by high blood sugar in diabetics and reduce the risk of developing type II diabetes in the first place. The Importance of Vitamin K Vitamin K is found in green leafy vegetables, fermented foods, and some animal products, particularly organ meats. It occurs in two general forms, vitamin K1 and vitamin K2.1 Vitamin K is required for the proper function and activation of different proteins known as vitamin K-dependent proteins. These proteins include several clotting factors that control blood coagulation as well as osteocalcin, a protein tied to vascular and bone health. Some of these vitamin K-dependent proteins help keep calcium in the bones, and out of blood vessels. Calcified blood vessels are one of the hallmarks of atherosclerosis and vascular dysfunction. Without adequate vitamin K, the risk of cardiovascular disease, osteoporosis, and osteopenia rises.1,9 Other vitamin K-dependent proteins have favorable t effects on metabolic function.3,10 Link to Metabolic Health Multiple types of research indicate that Vitamin K2 intake may lower risk of developing type II diabetes.11 The vitamin's role in glucose homeostasis may be due in part to the activation of osteocalcin. In addition to its role in bone mineralization, osteocalcin stimulates healthy insulin and adiponectin expression.12 Studies show that people with higher intake of vitamin K tend to have better insulin sensitivity, better control of blood glucose levels, and a decreased risk of developing type II diabetes.3,5 In an observational study embedded in a randomized controlled trial of the Mediterranean diet for prevention of cardiovascular disease, men and women without cardiovascular disease were followed for 5.5 years. Dietary information was collected annually through questionnaires. It was found that baseline intake of vitamin K1 was lower in participants who developed diabetes during the study. It was also found that the risk of developing diabetes dropped by approximately 17% for every 100 mcg of vitamin K1 consumed per day. Subjects who increased their dietary vitamin K1 intake over those 5.5 years had a 51% reduction in risk for developing diabetes, compared with those who did not increase vitamin K intake. The authors concluded that dietary vitamin K1 is associated with reduced risk of type II diabetes.13 How It Works Vitamin K appears to improve insulin function and glucose metabolism in at least two main ways: Activating vitamin K-dependent proteins is involved in regulating glucose metabolism.3 Suppressing chronic inflammation and production of pro-inflammatory compounds, which is a major contributor to diminished insulin sensitivity and metabolic disease.3 Together, these actions could help reduce elevated glycemic markers and lower risk for diabetic complications. https://www.lifeextension.com/magazine/2024/10/vitamin-k-and-blood-sugar

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Provide as much detail as possible on the active ingredients in Zyrtec, Claritin, and other similar allergy medications. Also, what type of allergic reactions can happen from taking them? Provide your answer in two separate paragraphs, one for the active ingredients and one for the allergic reactions.

Many people use antihistamines to treat allergy symptoms. Zyrtec (cetirizine) and Claritin (loratadine) are two popular brands. They contain different compounds but appear to be equally effective. Antihistamines can reduce allergy symptoms, such as watering eyes, itchy skin, hives, and swelling. They may also help with dermatitis or mosquito bites, but manufacturers usually market them for specific allergies. Zyrtec is a brand name for the drug cetirizine. Claritin is the brand name for loratadine. Zyretc and Claritin are in the same class of medications. Both are second-generation antihistamines and generally work the same way in the body. Neither is clearly better than the other. In this article, we provide details about the differences between Zyrtec and Claritin. We also compare them to two other popular brands of antihistamines: Benadryl and Allegra. Zyrtec and Claritin are brand-name medications that people can buy over the counter (OTC). They are available in various forms, including pills, chewable tablets, and syrups. Regardless of marketing claims, little scientific evidence shows that either is more effective. Active ingredients Zyrtec and Claritin have different active compounds. Zyrtec contains cetirizine hydrochloride, while Claritin contains loratadine. Drowsiness Zyrtec and Claritin are second-generation antihistamines. They are less likely to make a person feel drowsy or otherwise affect alertness than older, first-generation antihistamines. The labeling of Zyrtec says that a person should not take it when driving a vehicle or using machinery. People should avoid taking Zyrtec with alcohol or other medicines that could cause drowsiness. Timescales Zyrtec and Claritin are effective for about 24 hours. A person should only take one dose per day. The body absorbs both antihistamines quickly, but Zyrtec seems to work faster for some people. A 2019 article states that antihistamines reach their peak concentration between 30 minutes and 3 hours after swallowing them. Comparisons with other allergy medications Researchers are often studying, comparing, and improving antihistamines. Other popular brands on the market today are Allegra and Benadryl. Allegra: Allegra is non-sedating, so drowsiness is not a common side effect, although it is possible. Allegra is also a second-generation antihistamine. Benadryl: This can last up to 24 hours, which is longer than the other three. It aims to treat minor skin reactions and seasonal allergies. Benadryl is a first-generation antihistamine, which makes it sedating, so people tend to feel drowsy after taking it. How do allergy medications work? When people come into contact with an allergen, their immune system reacts and produces a chemical called histamine. Histamine causes many allergy symptoms, including inflammation of the skin or sinuses, pain, redness, and wheezing. Immune responses also encourage extra mucus to develop, which helps to clear allergens from the nose and throat. Allergy medications block histamine responses. This dulls the body’s response to minor or harmless allergens, such as pollen, dust, and pet dander. Precautions Claritin and Zyrtec are effective and safe for most people with minor allergies. However, as with all medications, there may be some side effects. Side effects Everyone reacts to medications differently, but Claritin and Zyrtec may have the following side effects: drowsiness, which is more likely when taking Zyrtec than Claritin a headache dizziness or light-headedness a sore throat dry mouth constipation or diarrhea abdominal cramps and pain eye redness Allergic reactions Some people experience a severe allergic response called anaphylaxis after taking antihistamines. A person should seek emergency medical attention if any of the following symptoms are present: hives a swollen throat swollen lips or face trouble breathing or other respiratory symptoms a racing heartbeat Children Some antihistamines are safe for children, but it is a good idea to talk with a doctor or pharmacist and check the label carefully before giving antihistamines to a child. Pregnancy A 2020 article examined the association between antihistamine use during early pregnancy and birth defects. Contrary to findings from older studies, the authors stated there was a lack of evidence to support an association. The American College of Obstetricians and Gynecologists states that Zyrtec (citirizine) and Claritin (loratadine) may be safe during pregnancy. The labeling for Zyrtec states that it is unsuitable during breastfeeding. Pregnant people should check with a doctor before using an antihistamine or any other drug.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Provide as much detail as possible on the active ingredients in Zyrtec, Claritin, and other similar allergy medications. Also, what type of allergic reactions can happen from taking them? Provide your answer in two separate paragraphs, one for the active ingredients and one for the allergic reactions. <TEXT> Many people use antihistamines to treat allergy symptoms. Zyrtec (cetirizine) and Claritin (loratadine) are two popular brands. They contain different compounds but appear to be equally effective. Antihistamines can reduce allergy symptoms, such as watering eyes, itchy skin, hives, and swelling. They may also help with dermatitis or mosquito bites, but manufacturers usually market them for specific allergies. Zyrtec is a brand name for the drug cetirizine. Claritin is the brand name for loratadine. Zyretc and Claritin are in the same class of medications. Both are second-generation antihistamines and generally work the same way in the body. Neither is clearly better than the other. In this article, we provide details about the differences between Zyrtec and Claritin. We also compare them to two other popular brands of antihistamines: Benadryl and Allegra. Zyrtec and Claritin are brand-name medications that people can buy over the counter (OTC). They are available in various forms, including pills, chewable tablets, and syrups. Regardless of marketing claims, little scientific evidence shows that either is more effective. Active ingredients Zyrtec and Claritin have different active compounds. Zyrtec contains cetirizine hydrochloride, while Claritin contains loratadine. Drowsiness Zyrtec and Claritin are second-generation antihistamines. They are less likely to make a person feel drowsy or otherwise affect alertness than older, first-generation antihistamines. The labeling of Zyrtec says that a person should not take it when driving a vehicle or using machinery. People should avoid taking Zyrtec with alcohol or other medicines that could cause drowsiness. Timescales Zyrtec and Claritin are effective for about 24 hours. A person should only take one dose per day. The body absorbs both antihistamines quickly, but Zyrtec seems to work faster for some people. A 2019 article states that antihistamines reach their peak concentration between 30 minutes and 3 hours after swallowing them. Comparisons with other allergy medications Researchers are often studying, comparing, and improving antihistamines. Other popular brands on the market today are Allegra and Benadryl. Allegra: Allegra is non-sedating, so drowsiness is not a common side effect, although it is possible. Allegra is also a second-generation antihistamine. Benadryl: This can last up to 24 hours, which is longer than the other three. It aims to treat minor skin reactions and seasonal allergies. Benadryl is a first-generation antihistamine, which makes it sedating, so people tend to feel drowsy after taking it. How do allergy medications work? When people come into contact with an allergen, their immune system reacts and produces a chemical called histamine. Histamine causes many allergy symptoms, including inflammation of the skin or sinuses, pain, redness, and wheezing. Immune responses also encourage extra mucus to develop, which helps to clear allergens from the nose and throat. Allergy medications block histamine responses. This dulls the body’s response to minor or harmless allergens, such as pollen, dust, and pet dander. Precautions Claritin and Zyrtec are effective and safe for most people with minor allergies. However, as with all medications, there may be some side effects. Side effects Everyone reacts to medications differently, but Claritin and Zyrtec may have the following side effects: drowsiness, which is more likely when taking Zyrtec than Claritin a headache dizziness or light-headedness a sore throat dry mouth constipation or diarrhea abdominal cramps and pain eye redness Allergic reactions Some people experience a severe allergic response called anaphylaxis after taking antihistamines. A person should seek emergency medical attention if any of the following symptoms are present: hives a swollen throat swollen lips or face trouble breathing or other respiratory symptoms a racing heartbeat Children Some antihistamines are safe for children, but it is a good idea to talk with a doctor or pharmacist and check the label carefully before giving antihistamines to a child. Pregnancy A 2020 article examined the association between antihistamine use during early pregnancy and birth defects. Contrary to findings from older studies, the authors stated there was a lack of evidence to support an association. The American College of Obstetricians and Gynecologists states that Zyrtec (citirizine) and Claritin (loratadine) may be safe during pregnancy. The labeling for Zyrtec states that it is unsuitable during breastfeeding. Pregnant people should check with a doctor before using an antihistamine or any other drug. https://www.medicalnewstoday.com/articles/321465#comparisons

You may only use information from the text in the prompt; use no outside or internal sources of knowledge or information.

What's Biden's involvement with this?

U.S. Policies Several executive branch and congressional actions have set the stage for increased development and deployment of offshore wind energy on the U.S. OCS.13 For example, Section 388 of the Energy Policy Act of 2005 (P.L. 109-58) amended the Outer Continental Shelf Lands Act (43 U.S.C. §§1331-1356c) to authorize the Secretary of the Interior to offer leases, easements, and rights-of-way for offshore renewable energy activities on the U.S. OCS.14 BOEM is the lead agency for the U.S. OCS renewable energy leasing program.15 In the 117th Congress, Section 50251 of the Inflation Reduction Act of 2022 (P.L. 117-196) expanded BOEM’s authority to pursue offshore wind leasing in federal waters in the southeastern Atlantic region, in the eastern Gulf of Mexico, and off U.S. territories.16 On the executive side, the Biden Administration suggested a doubling of offshore wind by 2030 as one potential approach to address climate change in Executive Order (E.O.) 14008, “Tackling the Climate Crisis at Home and Abroad.”17 In March 2021, the Biden Administration announced a government-wide effort to deploy 30 gigawatts (or 30,000 megawatts) of offshore wind energy by 2030.18 In September 2022, the Administration announced a related goal to deploy 15 gigawatts (or 15,000 megawatts) of installed floating offshore wind (i.e., structures that are not set into the ocean floor) by 2035.19 As of December 2023, BOEM has conducted 12 competitive wind energy lease sales for areas on the OCS, representing more than 2.5 million acres of commercial wind energy lease areas offshore of Delaware, Louisiana, Maryland, Massachusetts, New Jersey, New York, North Carolina, Rhode Island, South Carolina, Virginia, and California.20 Background on Offshore Wind Energy Project Development Stakeholders have expressed concerns regarding potential impacts to the marine ecosystem and associated species that pertain to offshore wind project activities associated with site development, construction, operation, and decommissioning.21 The following sections provide background on offshore wind energy turbine structures and discuss activities associated with offshore wind projects, including the potential impacts of these activities on the marine ecosystem and species. Potential Impacts of Offshore Wind Energy on the Marine Ecosystem and Associated Species Offshore wind projects may affect the marine ecosystem and associated species. Not all impacts may be adverse; some may be beneficial (e.g., the artificial reef effect, discussed below). In general, OWF activities can impact wildlife through atmospheric and oceanic change,43 • marine habitat alteration, • collision risk, • electromagnetic field (EMF) effects associated with power cables,44 • noise effects, and • water quality (e.g., pollution).45 The scientific literature analyzes the short-term adverse impacts and benefits of offshore wind development to marine mammals, invertebrates, fish, sea turtles, birds, bats, and other components of the marine ecosystem (Table 1).46 Modeling and observational studies (mostly derived from the North Sea) show that most impacts (e.g., habitat alteration) occur within the immediate vicinity of the wind turbine array, with other impacts (e.g., noise effects) extending up to tens of kilometers outside the array.47 Some of these analyses use land-based wind energy observations to model potential offshore wind scenarios, and other analyses extrapolate observations from existing OWFs (again, mostly in the North Sea) to planned offshore wind energy projects. Other potential impacts are informed by laboratory studies mimicking conditions (e.g., noise levels) often associated with offshore wind projects. The sections below discuss the potential OWF impacts (both adverse and beneficial) to the ocean environment and selected wildlife. Issues for Congress The full extent of impacts of offshore wind activities on the marine ecosystem of the U.S. OCS remains unclear, in part because the development of U.S. offshore wind projects is relatively recent. If interest in the climate mitigation benefits derived from offshore wind energy grows in the United States and BOEM continues to issue leases for offshore wind development, Congress may continue to consider how offshore wind energy development may impact the marine ecosystem and associated species.231 In the 118th Congress, some Members called for additional research into the potential harm offshore wind projects may cause to marine wildlife or expressed concern about the potential impacts offshore wind activities might have on other ocean uses (e.g., H.R. 1).

You may only use information from the text in the prompt; use no outside or internal sources of knowledge or information. What's Biden's involvement with this? U.S. Policies Several executive branch and congressional actions have set the stage for increased development and deployment of offshore wind energy on the U.S. OCS.13 For example, Section 388 of the Energy Policy Act of 2005 (P.L. 109-58) amended the Outer Continental Shelf Lands Act (43 U.S.C. §§1331-1356c) to authorize the Secretary of the Interior to offer leases, easements, and rights-of-way for offshore renewable energy activities on the U.S. OCS.14 BOEM is the lead agency for the U.S. OCS renewable energy leasing program.15 In the 117th Congress, Section 50251 of the Inflation Reduction Act of 2022 (P.L. 117-196) expanded BOEM’s authority to pursue offshore wind leasing in federal waters in the southeastern Atlantic region, in the eastern Gulf of Mexico, and off U.S. territories.16 On the executive side, the Biden Administration suggested a doubling of offshore wind by 2030 as one potential approach to address climate change in Executive Order (E.O.) 14008, “Tackling the Climate Crisis at Home and Abroad.”17 In March 2021, the Biden Administration announced a government-wide effort to deploy 30 gigawatts (or 30,000 megawatts) of offshore wind energy by 2030.18 In September 2022, the Administration announced a related goal to deploy 15 gigawatts (or 15,000 megawatts) of installed floating offshore wind (i.e., structures that are not set into the ocean floor) by 2035.19 As of December 2023, BOEM has conducted 12 competitive wind energy lease sales for areas on the OCS, representing more than 2.5 million acres of commercial wind energy lease areas offshore of Delaware, Louisiana, Maryland, Massachusetts, New Jersey, New York, North Carolina, Rhode Island, South Carolina, Virginia, and California.20 Background on Offshore Wind Energy Project Development Stakeholders have expressed concerns regarding potential impacts to the marine ecosystem and associated species that pertain to offshore wind project activities associated with site development, construction, operation, and decommissioning.21 The following sections provide background on offshore wind energy turbine structures and discuss activities associated with offshore wind projects, including the potential impacts of these activities on the marine ecosystem and species. Potential Impacts of Offshore Wind Energy on the Marine Ecosystem and Associated Species Offshore wind projects may affect the marine ecosystem and associated species. Not all impacts may be adverse; some may be beneficial (e.g., the artificial reef effect, discussed below). In general, OWF activities can impact wildlife through atmospheric and oceanic change,43 • marine habitat alteration, • collision risk, • electromagnetic field (EMF) effects associated with power cables,44 • noise effects, and • water quality (e.g., pollution).45 The scientific literature analyzes the short-term adverse impacts and benefits of offshore wind development to marine mammals, invertebrates, fish, sea turtles, birds, bats, and other components of the marine ecosystem (Table 1).46 Modeling and observational studies (mostly derived from the North Sea) show that most impacts (e.g., habitat alteration) occur within the immediate vicinity of the wind turbine array, with other impacts (e.g., noise effects) extending up to tens of kilometers outside the array.47 Some of these analyses use land-based wind energy observations to model potential offshore wind scenarios, and other analyses extrapolate observations from existing OWFs (again, mostly in the North Sea) to planned offshore wind energy projects. Other potential impacts are informed by laboratory studies mimicking conditions (e.g., noise levels) often associated with offshore wind projects. The sections below discuss the potential OWF impacts (both adverse and beneficial) to the ocean environment and selected wildlife. Issues for Congress The full extent of impacts of offshore wind activities on the marine ecosystem of the U.S. OCS remains unclear, in part because the development of U.S. offshore wind projects is relatively recent. If interest in the climate mitigation benefits derived from offshore wind energy grows in the United States and BOEM continues to issue leases for offshore wind development, Congress may continue to consider how offshore wind energy development may impact the marine ecosystem and associated species.231 In the 118th Congress, some Members called for additional research into the potential harm offshore wind projects may cause to marine wildlife or expressed concern about the potential impacts offshore wind activities might have on other ocean uses (e.g., H.R. 1).

Please answer the question using only the provided context. Format your answer as a list.

How can the Adobe Experience Platform make a business more profitable?

Adobe Experience Platform helps customers to centralise and standardise their customer data and content across the enterprise – powering 360° customer profiles, enabling data science, and data governance to drive real-time personalised experiences. Experience Platform provides services that includes capabilities for data ingestion, wrangling and analysing data and building predictive models and next best action. Experience Platform makes the data, content and insights available to experience-delivery systems to act upon in real time, yielding compelling experiences in the relevant moment. With Experience Platform, enterprises will be able to utilise completely coordinated marketing and analytics solutions for driving meaningful customer interactions, leading to positive business results. An integral part of Experience Platform is sharing customer experience data to improve experiences for our customers as they work to deliver real-time experiences through our open and extensible platform. Companies want to leverage their customer experience data and share data and insights across all their experience applications (both Adobe applications and third-party applications). Sharing customer experience data in multiple formats from multiple sources can require too much time and too many resources. Adobe’s Experience Data Model (XDM) is a formal specification that you can integrate into your own data model to create a true 360-degree view of your customer, which saves you time and makes moving your data into Adobe Experience Cloud products a seamless process. Company executives in a variety of industries have found themselves thinking about a single issue: how to create a better user experience by delivering the right offer (or right message) at the right time. In order to find an answer to that issue, we need to understand the entire journey of a customer across multiple touchpoints both online and offline. It’s not enough knowing how the customer interacts within a website. You also have to know how the customer responds to emails and how they respond to any offline touchpoints (such as customer support calls or marketing postcards). Knowing the details of the complete journey will give businesses information they need for better personalisation and that will allow them to use machine learning to analyse the journey and deliver an individualised experience. Nine in ten marketers say data is their most underutilised asset. Why aren’t they deriving more value from the terabytes of information they collect? Primarily, it’s because that data isn’t immediately usable. Information compiled from varied sources — like websites, emails, sales, third-party vendors and even offline channels — tends to be siloed and structured in different formats. Even when one department within a firm gets relevant data into a format it can understand, the resulting intel is still largely unintelligible to other teams and departments. If all that data were translated into a single language — one that is equally useful and informative to sales representatives, IT departments, social-media marketers and customer service reps — companies could offer customers more compelling, personalised experiences in real time. Adobe’s Experience Data Model (XDM) is a formal specification used to describe this journey of experiences, as well as the resulting actions and events. XDM describes not only the journey, but also the measurement, content offers and other details of the journey. XDM is more than just a “data dictionary” for companies working with data from customer experiences — it’s a complete language for the experience business. XDM has been developed by Adobe as a way to make experience data easier to interpret and to share. Companies have been chasing the 360-degree customer view for years. The biggest problem is that every bit of data seems to be in a different format or on a different platform. You have your website, your email offers, your customer support system, your retail store and a rewards card, not to mention your search, display, social and video advertising across the web. Many of the systems you use to track those items don’t talk to each other or even store the information in a format the other systems can use. Since you want to use machine learning to derive insights and intelligence from the data, and then use those insights to drive company actions, those separate systems make getting a better view of your customer a difficult and time-consuming task. How can you talk about delivering a personalised experience for your customers if every system has a different definition of who the customer is? To make all these disparate data sets work together and be understood, Data Engineers and Data Scientists are in a constant process of translating and re-translating the data at every step. A large amount of that time is spent understanding the structure of the data before they can turn the data into something meaningful that you can use to create a better experience for your customers. But streamlining that data is easier said than done. Almost 40 percent of advertisers employ three or more data management platforms and 44 percent use three or more analytics platforms. By juggling multiple different data platforms, companies are more likely drop sales leads. Data flowing in from a company’s smartphone app, for instance, might be in a completely different language than the data acquired from an email marketing campaign, a third-party vendor or from the point of sale. The average data scientist spends about 80 percent of their day preparing raw data for analysis, according to a recent poll from data mining company CrowdFlower. Every hour spent cleaning and structuring data is time that could be better spent drawing useful insights from that data, so companies can devise engaging customer experiences. Imagine if sales and marketing data existed in a single, standardised language from the moment it’s compiled — the same way Adobe standardised PDF for documents. Every business is an Experience Business. Whether you’re selling a product, a service or even an event, as long as another person is expected to interact with your company or product or service, then you are creating an experience. This is especially true for any business (or department) that deals with a customer’s ongoing interaction, such as customer support or loyalty clubs. XDM is a specification that describes the elements of those interactions. XDM can describe a consumer’s preferences and qualify what audiences they are part of and then categorise information about their online journey (such as what buttons they click on or what they add to a shopping cart). XDM can also define offline interactions such as loyalty-club memberships. XDM is a core part of the Adobe Experience Platform, built with partners and global brands that are strategically investing in this shared vision of omnipresent and consistent first-class customer experience. Modern customer interactions are unique because they go beyond what historically common data modelling can support. Interacting with digital audiences requires capabilities such as engaging content, insights from data at scale, complete data awareness, identity management, unified profiles, omni-channel and experiencecentric metadata, and the blending of real-time with historical behavioural data. Often, this data comes from multiple different vendors representing online behaviour across web and mobile and offline behavior for instore purchases, demographic information and user preferences. It is a labour-intensive process to combine all of these disparate data sources to get a 360-degree view of a consumer and speak to them with one voice across the various channels. XDM is the language to express these experiences.

Adobe Experience Platform helps customers to centralise and standardise their customer data and content across the enterprise – powering 360° customer profiles, enabling data science, and data governance to drive real-time personalised experiences. Experience Platform provides services that includes capabilities for data ingestion, wrangling and analysing data and building predictive models and next best action. Experience Platform makes the data, content and insights available to experience-delivery systems to act upon in real time, yielding compelling experiences in the relevant moment. With Experience Platform, enterprises will be able to utilise completely coordinated marketing and analytics solutions for driving meaningful customer interactions, leading to positive business results. An integral part of Experience Platform is sharing customer experience data to improve experiences for our customers as they work to deliver real-time experiences through our open and extensible platform. Companies want to leverage their customer experience data and share data and insights across all their experience applications (both Adobe applications and third-party applications). Sharing customer experience data in multiple formats from multiple sources can require too much time and too many resources. Adobe’s Experience Data Model (XDM) is a formal specification that you can integrate into your own data model to create a true 360-degree view of your customer, which saves you time and makes moving your data into Adobe Experience Cloud products a seamless process. Company executives in a variety of industries have found themselves thinking about a single issue: how to create a better user experience by delivering the right offer (or right message) at the right time. In order to find an answer to that issue, we need to understand the entire journey of a customer across multiple touchpoints both online and offline. It’s not enough knowing how the customer interacts within a website. You also have to know how the customer responds to emails and how they respond to any offline touchpoints (such as customer support calls or marketing postcards). Knowing the details of the complete journey will give businesses information they need for better personalisation and that will allow them to use machine learning to analyse the journey and deliver an individualised experience. Nine in ten marketers say data is their most underutilised asset. Why aren’t they deriving more value from the terabytes of information they collect? Primarily, it’s because that data isn’t immediately usable. Information compiled from varied sources — like websites, emails, sales, third-party vendors and even offline channels — tends to be siloed and structured in different formats. Even when one department within a firm gets relevant data into a format it can understand, the resulting intel is still largely unintelligible to other teams and departments. If all that data were translated into a single language — one that is equally useful and informative to sales representatives, IT departments, social-media marketers and customer service reps — companies could offer customers more compelling, personalised experiences in real time. Adobe’s Experience Data Model (XDM) is a formal specification used to describe this journey of experiences, as well as the resulting actions and events. XDM describes not only the journey, but also the measurement, content offers and other details of the journey. XDM is more than just a “data dictionary” for companies working with data from customer experiences — it’s a complete language for the experience business. XDM has been developed by Adobe as a way to make experience data easier to interpret and to share. Companies have been chasing the 360-degree customer view for years. The biggest problem is that every bit of data seems to be in a different format or on a different platform. You have your website, your email offers, your customer support system, your retail store and a rewards card, not to mention your search, display, social and video advertising across the web. Many of the systems you use to track those items don’t talk to each other or even store the information in a format the other systems can use. Since you want to use machine learning to derive insights and intelligence from the data, and then use those insights to drive company actions, those separate systems make getting a better view of your customer a difficult and time-consuming task. How can you talk about delivering a personalised experience for your customers if every system has a different definition of who the customer is? To make all these disparate data sets work together and be understood, Data Engineers and Data Scientists are in a constant process of translating and re-translating the data at every step. A large amount of that time is spent understanding the structure of the data before they can turn the data into something meaningful that you can use to create a better experience for your customers. But streamlining that data is easier said than done. Almost 40 percent of advertisers employ three or more data management platforms and 44 percent use three or more analytics platforms. By juggling multiple different data platforms, companies are more likely drop sales leads. Data flowing in from a company’s smartphone app, for instance, might be in a completely different language than the data acquired from an email marketing campaign, a third-party vendor or from the point of sale. The average data scientist spends about 80 percent of their day preparing raw data for analysis, according to a recent poll from data mining company CrowdFlower. Every hour spent cleaning and structuring data is time that could be better spent drawing useful insights from that data, so companies can devise engaging customer experiences. Imagine if sales and marketing data existed in a single, standardised language from the moment it’s compiled — the same way Adobe standardised PDF for documents. Every business is an Experience Business. Whether you’re selling a product, a service or even an event, as long as another person is expected to interact with your company or product or service, then you are creating an experience. This is especially true for any business (or department) that deals with a customer’s ongoing interaction, such as customer support or loyalty clubs. XDM is a specification that describes the elements of those interactions. XDM can describe a consumer’s preferences and qualify what audiences they are part of and then categorise information about their online journey (such as what buttons they click on or what they add to a shopping cart). XDM can also define offline interactions such as loyalty-club memberships. XDM is a core part of the Adobe Experience Platform, built with partners and global brands that are strategically investing in this shared vision of omnipresent and consistent first-class customer experience. Modern customer interactions are unique because they go beyond what historically common data modelling can support. Interacting with digital audiences requires capabilities such as engaging content, insights from data at scale, complete data awareness, identity management, unified profiles, omni-channel and experiencecentric metadata, and the blending of real-time with historical behavioural data. Often, this data comes from multiple different vendors representing online behaviour across web and mobile and offline behavior for instore purchases, demographic information and user preferences. It is a labour-intensive process to combine all of these disparate data sources to get a 360-degree view of a consumer and speak to them with one voice across the various channels. XDM is the language to express these experiences. Please answer the question using only the provided context. Format your answer as a list. How can the Adobe Experience Platform make a business more profitable?

Answer the question using only the information provided below. If the question has multiple items in the answer then provide the answer in a numbered list. Otherwise, provide the answer in no more than three paragraphs.

What risks or concerns have been identified regarding the use of facial recognition technology by law enforcement agencies?

Law enforcement agencies’ use of facial recognition technology (FRT), while not a new practice, has received increased attention from policymakers and the public. In the course of carrying out their duties, federal law enforcement agencies may use FRT for a variety of purposes. For instance, the Federal Bureau of Investigation (FBI) uses the technology to aid its investigations, and the bureau provides facial recognition assistance to federal, state, local, and tribal law enforcement partners. State, local, and tribal law enforcement have also adopted facial recognition software systems to assist in various phases of investigations. In addition, border officials use facial recognition for identity verification purposes. The use of FRT by law enforcement agencies has spurred questions on a range of topics. Some primary concerns revolve around the accuracy of the technology, including potential race-, gender-, and age-related biases; the collection, retention, and security of images contained in various facial recognition databases; public notification regarding the use of facial recognition and other image capturing technology; and policies or standards governing law enforcement agencies’ use of the technology. Some of these concerns have manifested in actions such as federal, state, and city efforts to prohibit or bound law enforcement agencies’ use of FRT. In addition, some companies producing facial recognition software, such as Microsoft, IBM, and Amazon, have enacted new barriers to law enforcement using their technologies. This report provides an overview of federal law enforcement agencies’ use of FRT, including the current status of scientific standards for its use. The report includes a discussion of how FRT may be used by law enforcement agencies with traditional policing missions as well as by those charged with securing the U.S. borders. It also discusses considerations for policymakers debating whether or how to influence federal, state, and local law enforcement agencies’ use of FRT. The term facial recognition technology can have different meanings for law enforcement agencies, policymakers, and the public, and the process of using facial recognition in a law enforcement context can involve various technologies and actors. Broadly, as technology experts have noted, “[t]here is no one standard system design for facial recognition systems. Not only do organizations build their systems differently, and for different environments, but they also use different terms to describe how their systems work.” 3 The following key terms are provided to help in understanding facial recognition technologies and processes in this report. 4 Face detection technology determines whether a digital image contains a face. Facial classification algorithms analyze a face image to produce an estimate of age, sex, or some other property, but do not identify the individual. An example application of this would be retail stores using facial classification to gather data on the gender and age ranges of people visiting a store, without identifying each shopper individually. Facial comparison and facial identification are often used in the same context. They involve a human manually examining the differences and similarities between facial images, or between a live subject and facial images, for the purpose of determining if they represent the same person. Facial comparison has three broad categories: assessment, review, and examination. Facial assessment is a quick image-to-image or image-to-person comparison, typically carried out in screening or access control situations, and is the least rigorous form of facial comparison. Facial review (often used in investigative, operational, or intelligence gathering applications) and facial examination (often used in a forensic applications) are increasingly rigorous levels of image comparison and should involve verification by an additional reviewer or examiner. They may involve a formal, systematic examination of facial images. Facial recognition broadly involves the automated searching of a facial image (a probe) against a known collection or database of photos. Facial recognition algorithms compare identity information from facial features in two face image samples and produce a measure of similarity (sometimes called a match score) between them; this information can be used to determine whether the same person is in both images. Images that have a similarity score above a defined threshold are presented to the user. There are two ways in which facial recognition algorithms work to compare images: • One-to-one verification algorithms compare a photo of someone claiming a specific identity with a stored image(s) of that known identity to determine if it is the same person. Uses of these algorithms can include unlocking a smartphone and verifying identities at a security checkpoint. • One-to-many identification search algorithms compare features of a probe photo with all those in a gallery of images. The algorithms can provide either a fixed number of the most similar candidates, or all candidates with a similarity score above a preset threshold, for human review. These algorithms may be used for purposes such as identifying potential suspect leads from a mugshot database. Probe refers to the facial image or template searched against a gallery or database of photos in a facial recognition system. Real-time facial recognition involves facial recognition algorithms that can be used while a video recording is taking place in order to determine in real time whether an individual in a video matches with a list of candidates in a database of photos. Threshold refers to any real number against which similarity scores are compared to produce a verification decision or gallery of images. Law enforcement agencies’ use of FRT has received attention from policymakers and the public over the past several years. There have been heightened concerns following several revelations, including that Clearview AI, a company that developed image-search technology used by law enforcement agencies around the country, had amassed a database of over 3 billion images against which probe photos could be compared. FRT is one of several biometric technologies employed by law enforcement agencies, which also include fingerprint, palm print, DNA and iris scans. FRT can be used by law enforcement for a variety of purposes such as generating investigative leads, identifying victims of crimes, facilitating the examination of forensic evidence, and helping verify the identity of individuals being released from prison. Press releases and statements from the Department of Justice highlight how the technology has been used in the criminal justice system. FRT has been used to help generate suspect leads. In one case, FBI agents used the technology, via the Mississippi Fusion Center, to identify a potential suspect in an interstate stalking case who had allegedly been harassing high school girls through their Twitter accounts.The suspect was later sentenced to 46 months imprisonment and three years of supervised release for this stalking.FRT may also be used to help identify victims. For example, officials have noted FRT was used to help identify “an accident victim lying unconscious on the side of the road.”FRT, along with other pieces of evidence, has been used to support probable cause in affidavits in support of criminal complaints. In one case, an FBI agent cited the use of FRT in a criminal complaint against a bank robbery suspect. The agent noted that images from the bank’s surveillance footage were run against facial recognition software, and a photo of the suspect was returned as a possible match. Investigators then interviewed associates of the suspect, who identified him as the man in the bank surveillance footage. Notably, the frequency and extent to which FRT is used at various phases of the criminal justice system (from generating leads and helping establish probable cause for an arrest or indictment, to serving as evidence in courtrooms) is unknown. It is most often discussed as being employed during investigations by law enforcement officials. Of note, FRT is generally used by law enforcement in one-to-many searches to produce a gallery of potential suspects ranked by similarity and not to provide a single affirmative match. As such, the technology currently might not be relied upon in the same way that other biometric evidence might. Rather, it is the results of an investigator’s facial review between a probe face and the gallery of images produced from running a probe face through facial recognition software that might be used as evidence contributing to an arrest and prosecution.

What risks or concerns have been identified regarding the use of facial recognition technology by law enforcement agencies? Answer the question using only the information provided below. If the question has multiple items in the answer then provide the answer in a numbered list. Otherwise, provide the answer in no more than three paragraphs. Law enforcement agencies’ use of facial recognition technology (FRT), while not a new practice, has received increased attention from policymakers and the public. In the course of carrying out their duties, federal law enforcement agencies may use FRT for a variety of purposes. For instance, the Federal Bureau of Investigation (FBI) uses the technology to aid its investigations, and the bureau provides facial recognition assistance to federal, state, local, and tribal law enforcement partners. State, local, and tribal law enforcement have also adopted facial recognition software systems to assist in various phases of investigations. In addition, border officials use facial recognition for identity verification purposes. The use of FRT by law enforcement agencies has spurred questions on a range of topics. Some primary concerns revolve around the accuracy of the technology, including potential race-, gender-, and age-related biases; the collection, retention, and security of images contained in various facial recognition databases; public notification regarding the use of facial recognition and other image capturing technology; and policies or standards governing law enforcement agencies’ use of the technology. Some of these concerns have manifested in actions such as federal, state, and city efforts to prohibit or bound law enforcement agencies’ use of FRT. In addition, some companies producing facial recognition software, such as Microsoft, IBM, and Amazon, have enacted new barriers to law enforcement using their technologies. This report provides an overview of federal law enforcement agencies’ use of FRT, including the current status of scientific standards for its use. The report includes a discussion of how FRT may be used by law enforcement agencies with traditional policing missions as well as by those charged with securing the U.S. borders. It also discusses considerations for policymakers debating whether or how to influence federal, state, and local law enforcement agencies’ use of FRT. The term facial recognition technology can have different meanings for law enforcement agencies, policymakers, and the public, and the process of using facial recognition in a law enforcement context can involve various technologies and actors. Broadly, as technology experts have noted, “[t]here is no one standard system design for facial recognition systems. Not only do organizations build their systems differently, and for different environments, but they also use different terms to describe how their systems work.” 3 The following key terms are provided to help in understanding facial recognition technologies and processes in this report. 4 Face detection technology determines whether a digital image contains a face. Facial classification algorithms analyze a face image to produce an estimate of age, sex, or some other property, but do not identify the individual. An example application of this would be retail stores using facial classification to gather data on the gender and age ranges of people visiting a store, without identifying each shopper individually. Facial comparison and facial identification are often used in the same context. They involve a human manually examining the differences and similarities between facial images, or between a live subject and facial images, for the purpose of determining if they represent the same person. Facial comparison has three broad categories: assessment, review, and examination. Facial assessment is a quick image-to-image or image-to-person comparison, typically carried out in screening or access control situations, and is the least rigorous form of facial comparison. Facial review (often used in investigative, operational, or intelligence gathering applications) and facial examination (often used in a forensic applications) are increasingly rigorous levels of image comparison and should involve verification by an additional reviewer or examiner. They may involve a formal, systematic examination of facial images. Facial recognition broadly involves the automated searching of a facial image (a probe) against a known collection or database of photos. Facial recognition algorithms compare identity information from facial features in two face image samples and produce a measure of similarity (sometimes called a match score) between them; this information can be used to determine whether the same person is in both images. Images that have a similarity score above a defined threshold are presented to the user. There are two ways in which facial recognition algorithms work to compare images: • One-to-one verification algorithms compare a photo of someone claiming a specific identity with a stored image(s) of that known identity to determine if it is the same person. Uses of these algorithms can include unlocking a smartphone and verifying identities at a security checkpoint. • One-to-many identification search algorithms compare features of a probe photo with all those in a gallery of images. The algorithms can provide either a fixed number of the most similar candidates, or all candidates with a similarity score above a preset threshold, for human review. These algorithms may be used for purposes such as identifying potential suspect leads from a mugshot database. Probe refers to the facial image or template searched against a gallery or database of photos in a facial recognition system. Real-time facial recognition involves facial recognition algorithms that can be used while a video recording is taking place in order to determine in real time whether an individual in a video matches with a list of candidates in a database of photos. Threshold refers to any real number against which similarity scores are compared to produce a verification decision or gallery of images. Law enforcement agencies’ use of FRT has received attention from policymakers and the public over the past several years. There have been heightened concerns following several revelations, including that Clearview AI, a company that developed image-search technology used by law enforcement agencies around the country, had amassed a database of over 3 billion images against which probe photos could be compared. FRT is one of several biometric technologies employed by law enforcement agencies, which also include fingerprint, palm print, DNA and iris scans. FRT can be used by law enforcement for a variety of purposes such as generating investigative leads, identifying victims of crimes, facilitating the examination of forensic evidence, and helping verify the identity of individuals being released from prison. Press releases and statements from the Department of Justice highlight how the technology has been used in the criminal justice system. FRT has been used to help generate suspect leads. In one case, FBI agents used the technology, via the Mississippi Fusion Center, to identify a potential suspect in an interstate stalking case who had allegedly been harassing high school girls through their Twitter accounts.The suspect was later sentenced to 46 months imprisonment and three years of supervised release for this stalking.FRT may also be used to help identify victims. For example, officials have noted FRT was used to help identify “an accident victim lying unconscious on the side of the road.”FRT, along with other pieces of evidence, has been used to support probable cause in affidavits in support of criminal complaints. In one case, an FBI agent cited the use of FRT in a criminal complaint against a bank robbery suspect. The agent noted that images from the bank’s surveillance footage were run against facial recognition software, and a photo of the suspect was returned as a possible match. Investigators then interviewed associates of the suspect, who identified him as the man in the bank surveillance footage. Notably, the frequency and extent to which FRT is used at various phases of the criminal justice system (from generating leads and helping establish probable cause for an arrest or indictment, to serving as evidence in courtrooms) is unknown. It is most often discussed as being employed during investigations by law enforcement officials. Of note, FRT is generally used by law enforcement in one-to-many searches to produce a gallery of potential suspects ranked by similarity and not to provide a single affirmative match. As such, the technology currently might not be relied upon in the same way that other biometric evidence might. Rather, it is the results of an investigator’s facial review between a probe face and the gallery of images produced from running a probe face through facial recognition software that might be used as evidence contributing to an arrest and prosecution.

[question] [user request] ===================== [text] [context document] ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

My doctor said I have a herniated disc. Is there something that can permanently help with this diagnosis? What are the pros and cons of each surgical option?

What to know about herniated disc surgery What is a herniated disc? Who needs surgery? Procedures Recovery Risks Alternatives Summary A person who has a herniated disc may experience pain that affects their daily activities. While it is not always necessary, some people may require herniated disc surgery to alleviate pain and other symptoms. The type of surgery a person has depends on several factors. These include the location of the herniated disc, the severity of the pain, and the disability it causes. In this article, we discuss the different types of herniated disc surgeries and their risks. We will also explore how long it takes to recover from herniated disc surgery. What is a herniated disc? The pain from a herniated disc may affect a person’s daily activities. The spine is made up of individual bones known as vertebrae. Intervertebral discs are discs of cartilage that sit between the vertebrae. The function of the intervertebral discs is to support the spine and act as shock absorbers between the vertebrae. There are normally 23 discs in the human spine. Each disc is made up of three components: Nucleus pulposus: This is the inner gel-like portion of the disc that gives the spine its flexibility and strength. Annulus fibrosis: This is a tough outer layer that surrounds the nucleus pulposus. Cartilaginous endplates: These are pieces of cartilage that sit between the disc and its adjoining vertebrae. In a herniated disc, the annulus fibrosis is torn or ruptured. This damage allows part of the nucleus pulposus to push through into the spinal canal. Sometimes, the herniated material can press on a nerve, causing pain and affecting movement. Each year, herniated discs affect around 5–20 of every 1,000 adults between the ages of 20 and 49 years old. A herniated disc can occur anywhere in the spine. The two most common locations are the lumbar spine and the cervical spine. The lumbar spine refers to the lower back, while the cervical spine refers to the neck region. Procedures There is a variety of procedures that a surgeon can carry out to treat a herniated disc. The purpose of herniated disc surgery is to ease pressure on the nerve, thereby alleviating pain and other symptoms. A doctor may use one of the following three techniques Source to alleviate pressure on the nerve: Open discectomy: The surgeon performs open surgery to remove the herniated section of the disc. Endoscopic spine surgery: The surgeon uses a long thin tube, or endoscope, to remove the herniated section of the disc. The procedure is minimally invasive, requiring a tiny incision. Only a small scar will form, resulting in a quicker recovery. Surgery on the core of the spinal disc: The surgeon uses instruments to access the core of the spinal disc then uses a vacuum to remove the core. This makes the spinal disc smaller, which reduces pressure on the nerve. The surgery is only possible if the outer layer of the disc is not damaged. Other surgical interventions for a herniated disc include: Laminotomy or laminectomy The lamina is a part of the vertebrae that covers and protects the spinal canal. Sometimes, doctors need to remove part or all of the lamina to repair a herniated disc. A laminotomy involves the removal of part of the lamina, while a laminectomy is removal of the entire lamina. Both procedures involve making a small incision down the center of the back or neck over the area of the herniated disc. After removing part or all of the lamina, the surgeon performs a discectomy to remove the herniated disc. Laminotomies and laminectomies can be lumbar or cervical: Lumbar procedures: These help to relieve leg pain or sciatic pain that a herniated disc causes in the lower back region. Cervical procedures: These help to relieve pain in the neck and upper limbs that a herniated disc causes in the neck region. Spinal fusion Following a laminotomy or laminectomy, a spinal fusion (SF) may be necessary to stabilize the spine. An SF involves joining two bones together with screws. People who have undergone an SF may experience pain and feel as if the treatment is restricting certain movements. The likelihood of needing an SF depends on the location of the herniated disc. Typically, lumbar laminotomies require an SF. Cervical laminotomies require an SF if the surgeon operates from the front of the neck. The same procedures rarely require an SF if the surgeon operates from the back of the neck. The point the surgeon works from depends on the exact location of the herniated disc. Some people who undergo laminotomy may be candidates for artificial disc surgery instead of an SF. Artificial disc surgery Artificial disc surgery (ADS) is an alternative to spinal fusion. In ADS, the surgeon replaces the damaged disc with an artificial one. A surgeon will usually associate this method with less pain and less restricted movement in comparison to SF procedures. Recovery process and timeline According to the North American Spine Society, people who undergo surgery for a herniated disc earlier rather than later may have a faster recovery time. They may also experience improved long term health. Typically, most people can go home 24 hours after a herniated disc operation. Some may even be able to go home the same day. Doctors recommend that people recovering from herniated disc surgery avoid the following activities for around 4 weeks: driving sitting for long periods lifting heavy weights bending over Some exercises may be beneficial for people who have had herniated disc surgery. However, they should consult their doctor or surgeon before attempting any strenuous activities. Sometimes, doctors may suggest rehabilitation therapy after surgery. People who follow a rehabilitation program after herniated disc surgery may achieve a shorter recovery time and improved mobility. Risks Discectomies hardly ever result in complications. However, in rare cases, people may experience the following: bleeding infections tears in the spine’s protective lining injury to the nerve In around 5% of people, the problematic disc may rupture again, causing symptoms to recur. Herniated disc surgery can be an effective treatment for many people with challenging pain. However, surgeons cannot guarantee that symptoms will disappear after surgery. Some people may continue to experience herniated disc pain after the recovery period. In some cases, the pain may worsen over time. Other treatment options Taking pain medication may ease symptoms of a herniated disc. People who develop a herniated disc should limit their activities for 2 to 3 days. Limiting movement will reduce inflammation at the site of the nerve. Although it may seem counterintuitive, doctors do not recommend bed rest, however. People who have pinched nerves in the neck and leg due to a herniated disc may try NSAIDs and physical therapy. If those treatments are ineffective, doctors may recommend other nonsurgical options, such as selective nerve root blocks. These treatments are local numbing agents that doctors inject into the spinal cord to alleviate herniated disc pain. Summary A herniated disc can cause disabling pain. In many cases, nonsurgical treatment options offer effective pain relief. If there is no improvement, a doctor may recommend herniated disc surgery. The type of surgical procedure a person undergoes depends on several factors. These include the location of the herniated disc, the severity of the pain, and level of disability it causes. Most people can return to their usual activities around 4 weeks after herniated disc surgery. People who follow a rehabilitation program after surgery may experience a shorter recovery time and better mobility.

[question] My doctor said I have a herniated disc. Is there something that can permanently help with this diagnosis? What are the pros and cons of each surgical option? ===================== [text] What to know about herniated disc surgery What is a herniated disc? Who needs surgery? Procedures Recovery Risks Alternatives Summary A person who has a herniated disc may experience pain that affects their daily activities. While it is not always necessary, some people may require herniated disc surgery to alleviate pain and other symptoms. The type of surgery a person has depends on several factors. These include the location of the herniated disc, the severity of the pain, and the disability it causes. In this article, we discuss the different types of herniated disc surgeries and their risks. We will also explore how long it takes to recover from herniated disc surgery. What is a herniated disc? The pain from a herniated disc may affect a person’s daily activities. The spine is made up of individual bones known as vertebrae. Intervertebral discs are discs of cartilage that sit between the vertebrae. The function of the intervertebral discs is to support the spine and act as shock absorbers between the vertebrae. There are normally 23 discs in the human spine. Each disc is made up of three components: Nucleus pulposus: This is the inner gel-like portion of the disc that gives the spine its flexibility and strength. Annulus fibrosis: This is a tough outer layer that surrounds the nucleus pulposus. Cartilaginous endplates: These are pieces of cartilage that sit between the disc and its adjoining vertebrae. In a herniated disc, the annulus fibrosis is torn or ruptured. This damage allows part of the nucleus pulposus to push through into the spinal canal. Sometimes, the herniated material can press on a nerve, causing pain and affecting movement. Each year, herniated discs affect around 5–20 of every 1,000 adults between the ages of 20 and 49 years old. A herniated disc can occur anywhere in the spine. The two most common locations are the lumbar spine and the cervical spine. The lumbar spine refers to the lower back, while the cervical spine refers to the neck region. Procedures There is a variety of procedures that a surgeon can carry out to treat a herniated disc. The purpose of herniated disc surgery is to ease pressure on the nerve, thereby alleviating pain and other symptoms. A doctor may use one of the following three techniques Source to alleviate pressure on the nerve: Open discectomy: The surgeon performs open surgery to remove the herniated section of the disc. Endoscopic spine surgery: The surgeon uses a long thin tube, or endoscope, to remove the herniated section of the disc. The procedure is minimally invasive, requiring a tiny incision. Only a small scar will form, resulting in a quicker recovery. Surgery on the core of the spinal disc: The surgeon uses instruments to access the core of the spinal disc then uses a vacuum to remove the core. This makes the spinal disc smaller, which reduces pressure on the nerve. The surgery is only possible if the outer layer of the disc is not damaged. Other surgical interventions for a herniated disc include: Laminotomy or laminectomy The lamina is a part of the vertebrae that covers and protects the spinal canal. Sometimes, doctors need to remove part or all of the lamina to repair a herniated disc. A laminotomy involves the removal of part of the lamina, while a laminectomy is removal of the entire lamina. Both procedures involve making a small incision down the center of the back or neck over the area of the herniated disc. After removing part or all of the lamina, the surgeon performs a discectomy to remove the herniated disc. Laminotomies and laminectomies can be lumbar or cervical: Lumbar procedures: These help to relieve leg pain or sciatic pain that a herniated disc causes in the lower back region. Cervical procedures: These help to relieve pain in the neck and upper limbs that a herniated disc causes in the neck region. Spinal fusion Following a laminotomy or laminectomy, a spinal fusion (SF) may be necessary to stabilize the spine. An SF involves joining two bones together with screws. People who have undergone an SF may experience pain and feel as if the treatment is restricting certain movements. The likelihood of needing an SF depends on the location of the herniated disc. Typically, lumbar laminotomies require an SF. Cervical laminotomies require an SF if the surgeon operates from the front of the neck. The same procedures rarely require an SF if the surgeon operates from the back of the neck. The point the surgeon works from depends on the exact location of the herniated disc. Some people who undergo laminotomy may be candidates for artificial disc surgery instead of an SF. Artificial disc surgery Artificial disc surgery (ADS) is an alternative to spinal fusion. In ADS, the surgeon replaces the damaged disc with an artificial one. A surgeon will usually associate this method with less pain and less restricted movement in comparison to SF procedures. Recovery process and timeline According to the North American Spine Society, people who undergo surgery for a herniated disc earlier rather than later may have a faster recovery time. They may also experience improved long term health. Typically, most people can go home 24 hours after a herniated disc operation. Some may even be able to go home the same day. Doctors recommend that people recovering from herniated disc surgery avoid the following activities for around 4 weeks: driving sitting for long periods lifting heavy weights bending over Some exercises may be beneficial for people who have had herniated disc surgery. However, they should consult their doctor or surgeon before attempting any strenuous activities. Sometimes, doctors may suggest rehabilitation therapy after surgery. People who follow a rehabilitation program after herniated disc surgery may achieve a shorter recovery time and improved mobility. Risks Discectomies hardly ever result in complications. However, in rare cases, people may experience the following: bleeding infections tears in the spine’s protective lining injury to the nerve In around 5% of people, the problematic disc may rupture again, causing symptoms to recur. Herniated disc surgery can be an effective treatment for many people with challenging pain. However, surgeons cannot guarantee that symptoms will disappear after surgery. Some people may continue to experience herniated disc pain after the recovery period. In some cases, the pain may worsen over time. Other treatment options Taking pain medication may ease symptoms of a herniated disc. People who develop a herniated disc should limit their activities for 2 to 3 days. Limiting movement will reduce inflammation at the site of the nerve. Although it may seem counterintuitive, doctors do not recommend bed rest, however. People who have pinched nerves in the neck and leg due to a herniated disc may try NSAIDs and physical therapy. If those treatments are ineffective, doctors may recommend other nonsurgical options, such as selective nerve root blocks. These treatments are local numbing agents that doctors inject into the spinal cord to alleviate herniated disc pain. Summary A herniated disc can cause disabling pain. In many cases, nonsurgical treatment options offer effective pain relief. If there is no improvement, a doctor may recommend herniated disc surgery. The type of surgical procedure a person undergoes depends on several factors. These include the location of the herniated disc, the severity of the pain, and level of disability it causes. Most people can return to their usual activities around 4 weeks after herniated disc surgery. People who follow a rehabilitation program after surgery may experience a shorter recovery time and better mobility. https://www.medicalnewstoday.com/articles/326780#who-needs-surgery ===================== [instruction] Answer the question using only the information provided in the context. Do not rely on external knowledge or sources.

Reference the prompt text for your answer only. Do not use outside sources or internal knowledge. If you cannot locate the information in the text, please respond with "I cannot locate the answer using the context block at this time."

Is it lawful to market flavored ENDS products?

Circuit Split over the Food and Drug Administration’s Denial of Applications Seeking to Market Flavored E-Cigarettes, Part 1 of 2 April 5, 2024 Electronic nicotine delivery system (ENDS) products—products that go by many common names, such as e-cigarettes and vape pens—are generally required to receive prior authorization from the Food and Drug Administration (FDA) before they can be lawfully marketed in the United States. Before FDA issued regulations in 2016 to subject these products to the premarket review process, however, many of them were already being sold on the U.S. market and were allowed to remain there while FDA implemented the application and review process. These products come in a variety of forms and flavors, from tobacco and menthol flavors based on the flavors of traditional combustible cigarettes to other flavors based on the flavors of fruit, candy, and other sweets (“flavored ENDS products”). While limited studies of certain ENDS products show that they contain substantially lower levels of toxins than combustible cigarettes, indicating a benefit to current adult smokers who switch completely to using ENDS products, flavored ENDS products have been shown to be particularly attractive to youth. In a 2016-2017 study, for instance, 93.2% of youth ENDS product users reported that their first use was with a flavored product. In 2018, the Surgeon General issued an advisory on the “e-cigarette epidemic among youth.” Since the initial deadline in September 2020 for ENDS product manufacturers to submit their premarket tobacco product applications (PMTAs), FDA has received millions of applications for ENDS products. To date, the agency has authorized 23 tobacco-flavored ENDS products for lawful marketing and has not authorized any flavored ENDS products. Many applicants that have received a marketing denial order (MDO) for their flavored ENDS products have filed petitions in U.S. Courts of Appeals throughout the country to challenge the denial of their PMTAs. Of the courts that have considered these petitions, the Second, Third, Fourth, Sixth, Seventh, Ninth, Tenth, and D.C. Circuits have sided with FDA and denied the petitions or requests to stay the agency’s MDOs. The Eleventh and Fifth Circuits, on the other hand, have sided with the ENDS manufacturers and vacated FDA’s MDOs, remanding the applications to FDA for reconsideration. This circuit split sets the stage for potential Supreme Court review regarding what information FDA may require applicants seeking to market flavored ENDS products to provide as part of their PMTAs. This two-part Sidebar examines the circuit split. Part I provides an overview of the Family Smoking Prevention and Tobacco Control Act (TCA) regulatory framework, relevant FDA actions related to ENDS products, and the agency’s review and denial of the PMTAs involving flavored ENDS products. Part II provides an overview of the litigation challenging those FDA orders, the court decisions to date, and certain preliminary observations for consideration by Congress.

Reference the prompt text for your answer only. Do not use outside sources or internal knowledge. If you cannot locate the information in the text, please respond with "I cannot locate the answer using the context block at this time." Question: Is it lawful to market flavored ENDS products? Circuit Split over the Food and Drug Administration’s Denial of Applications Seeking to Market Flavored E-Cigarettes, Part 1 of 2 April 5, 2024 Electronic nicotine delivery system (ENDS) products—products that go by many common names, such as e-cigarettes and vape pens—are generally required to receive prior authorization from the Food and Drug Administration (FDA) before they can be lawfully marketed in the United States. Before FDA issued regulations in 2016 to subject these products to the premarket review process, however, many of them were already being sold on the U.S. market and were allowed to remain there while FDA implemented the application and review process. These products come in a variety of forms and flavors, from tobacco and menthol flavors based on the flavors of traditional combustible cigarettes to other flavors based on the flavors of fruit, candy, and other sweets (“flavored ENDS products”). While limited studies of certain ENDS products show that they contain substantially lower levels of toxins than combustible cigarettes, indicating a benefit to current adult smokers who switch completely to using ENDS products, flavored ENDS products have been shown to be particularly attractive to youth. In a 2016-2017 study, for instance, 93.2% of youth ENDS product users reported that their first use was with a flavored product. In 2018, the Surgeon General issued an advisory on the “e-cigarette epidemic among youth.” Since the initial deadline in September 2020 for ENDS product manufacturers to submit their premarket tobacco product applications (PMTAs), FDA has received millions of applications for ENDS products. To date, the agency has authorized 23 tobacco-flavored ENDS products for lawful marketing and has not authorized any flavored ENDS products. Many applicants that have received a marketing denial order (MDO) for their flavored ENDS products have filed petitions in U.S. Courts of Appeals throughout the country to challenge the denial of their PMTAs. Of the courts that have considered these petitions, the Second, Third, Fourth, Sixth, Seventh, Ninth, Tenth, and D.C. Circuits have sided with FDA and denied the petitions or requests to stay the agency’s MDOs. The Eleventh and Fifth Circuits, on the other hand, have sided with the ENDS manufacturers and vacated FDA’s MDOs, remanding the applications to FDA for reconsideration. This circuit split sets the stage for potential Supreme Court review regarding what information FDA may require applicants seeking to market flavored ENDS products to provide as part of their PMTAs. This two-part Sidebar examines the circuit split. Part I provides an overview of the Family Smoking Prevention and Tobacco Control Act (TCA) regulatory framework, relevant FDA actions related to ENDS products, and the agency’s review and denial of the PMTAs involving flavored ENDS products. Part II provides an overview of the litigation challenging those FDA orders, the court decisions to date, and certain preliminary observations for consideration by Congress.

Your response should be based only on the text provided below. Do not use any outside resources or prior knowledge in formulating your answer.

Tell me in a bullet-pointed list what differential diagnoses of Hypertensive Retinopathy are not shared with HIV Retinopathy or with Diabetic Retinopathy.

Diabetic Retinopathy ■ Essentials of Diagnosis • May have decreased or fluctuating vision or floaters; often asymptomatic early in the course of the disease • Nonproliferative: Dot and blot hemorrhages, microaneurysms, hard exudates, cotton-wool spots, venous beading, and intraretinal microvascular abnormalities • Proliferative: Neovascularization of optic disk, retina, or iris; preretinal or vitreous hemorrhages; tractional retinal detachment ■ Differential Diagnosis • Hypertensive retinopathy • HIV retinopathy • Radiation retinopathy • Central or branch retinal vein occlusion • Ocular ischemic syndrome • Sickle cell retinopathy • Retinopathy of severe anemia • Embolization from intravenous drug abuse (talc retinopathy) • Collagen vascular disease • Sarcoidosis • Eales’ disease ■ Treatment • Ophthalmologic referral and regular follow-up in all diabetics • Laser photocoagulation, intravitreal Kenalog, intravitreal antiangiogenesis drugs (eg, Lucentis or Avastin) for macular edema and proliferative disease • Pars plana vitrectomy for nonclearing vitreous hemorrhage and tractional retinal detachment involving or threatening the macula ■ Pearl Though a debate about this has lasted decades, it appears that aggressive glycemic control prevents progression; be sure your patients understand and know their A1c. Reference El-Asrar AM, Al-Mezaine HS, Ola MS. Changing paradigms in the treatment of diabetic retinopathy. Curr Opin Ophthalmol 2009;20:532. [PMID: 19644368] 20 518 Current Essentials of Medicine HIV Retinopathy ■ Essentials of Diagnosis • Cotton-wool spots, intraretinal hemorrhages, microaneurysms seen on funduscopic examination in a patient with known or suspected HIV infection • Typically asymptomatic unless accompanied by other HIV-related retinal pathology (eg, cytomegalovirus retinitis) ■ Differential Diagnosis • Diabetic retinopathy • Hypertensive retinopathy • Radiation retinopathy • Retinopathy of severe anemia • Central or branch retinal vein occlusion • Sickle cell retinopathy • Embolization from intravenous drug abuse (talc retinopathy) • Sarcoidosis • Eales’ disease ■ Treatment • Treat the underlying HIV disease • Ophthalmologic referral is appropriate for any patient with HIV, especially with a low CD4 count and/or visual symptoms ■ Pearl HIV retinopathy is the most common ophthalmologic manifestation of HIV infection; it usually indicates a low CD4 count. Reference Holland GN. AIDS and ophthalmology: the first quarter century. Am J Ophthalmol 2008;145:397. [PMID: 18282490] Hypertensive Retinopathy ■ Essentials of Diagnosis • Usually asymptomatic; may have decreased vision • Generalized or localized retinal arteriolar narrowing, almost always bilateral • Arteriovenous crossing changes (AV nicking), retinal arteriolar sclerosis (copper or silver wiring), cotton-wool spots, hard exudates, flame-shaped hemorrhages, retinal edema, arterial macroaneurysms, chorioretinal atrophy • Optic disk edema in malignant hypertension ■ Differential Diagnosis • Diabetic retinopathy • Radiation retinopathy • HIV retinopathy • Central or branch retinal vein occlusion • Sickle cell retinopathy • Retinopathy of severe anemia • Embolization from intravenous drug abuse (talc retinopathy) • Autoimmune disease • Sarcoidosis • Eales’ disease ■ Treatment • Treat the hypertension • Ophthalmologic referral ■ Pearl The only pathognomonic funduscopic change of hypertension is focal arteriolar narrowing due to spasm, and it is typically seen in hypertensive crisis. Reference DellaCroce JT, Vitale AT. Hypertension and the eye. Curr Opin Ophthalmol 2008;19:493. [PMID: 18854694]

Your response should be based only on the text provided below. Do not use any outside resources or prior knowledge in formulating your answer. Diabetic Retinopathy ■ Essentials of Diagnosis • May have decreased or fluctuating vision or floaters; often asymptomatic early in the course of the disease • Nonproliferative: Dot and blot hemorrhages, microaneurysms, hard exudates, cotton-wool spots, venous beading, and intraretinal microvascular abnormalities • Proliferative: Neovascularization of optic disk, retina, or iris; preretinal or vitreous hemorrhages; tractional retinal detachment ■ Differential Diagnosis • Hypertensive retinopathy • HIV retinopathy • Radiation retinopathy • Central or branch retinal vein occlusion • Ocular ischemic syndrome • Sickle cell retinopathy • Retinopathy of severe anemia • Embolization from intravenous drug abuse (talc retinopathy) • Collagen vascular disease • Sarcoidosis • Eales’ disease ■ Treatment • Ophthalmologic referral and regular follow-up in all diabetics • Laser photocoagulation, intravitreal Kenalog, intravitreal antiangiogenesis drugs (eg, Lucentis or Avastin) for macular edema and proliferative disease • Pars plana vitrectomy for nonclearing vitreous hemorrhage and tractional retinal detachment involving or threatening the macula ■ Pearl Though a debate about this has lasted decades, it appears that aggressive glycemic control prevents progression; be sure your patients understand and know their A1c. Reference El-Asrar AM, Al-Mezaine HS, Ola MS. Changing paradigms in the treatment of diabetic retinopathy. Curr Opin Ophthalmol 2009;20:532. [PMID: 19644368] 20 518 Current Essentials of Medicine HIV Retinopathy ■ Essentials of Diagnosis • Cotton-wool spots, intraretinal hemorrhages, microaneurysms seen on funduscopic examination in a patient with known or suspected HIV infection • Typically asymptomatic unless accompanied by other HIV-related retinal pathology (eg, cytomegalovirus retinitis) ■ Differential Diagnosis • Diabetic retinopathy • Hypertensive retinopathy • Radiation retinopathy • Retinopathy of severe anemia • Central or branch retinal vein occlusion • Sickle cell retinopathy • Embolization from intravenous drug abuse (talc retinopathy) • Sarcoidosis • Eales’ disease ■ Treatment • Treat the underlying HIV disease • Ophthalmologic referral is appropriate for any patient with HIV, especially with a low CD4 count and/or visual symptoms ■ Pearl HIV retinopathy is the most common ophthalmologic manifestation of HIV infection; it usually indicates a low CD4 count. Reference Holland GN. AIDS and ophthalmology: the first quarter century. Am J Ophthalmol 2008;145:397. [PMID: 18282490] Hypertensive Retinopathy ■ Essentials of Diagnosis • Usually asymptomatic; may have decreased vision • Generalized or localized retinal arteriolar narrowing, almost always bilateral • Arteriovenous crossing changes (AV nicking), retinal arteriolar sclerosis (copper or silver wiring), cotton-wool spots, hard exudates, flame-shaped hemorrhages, retinal edema, arterial macroaneurysms, chorioretinal atrophy • Optic disk edema in malignant hypertension ■ Differential Diagnosis • Diabetic retinopathy • Radiation retinopathy • HIV retinopathy • Central or branch retinal vein occlusion • Sickle cell retinopathy • Retinopathy of severe anemia • Embolization from intravenous drug abuse (talc retinopathy) • Autoimmune disease • Sarcoidosis • Eales’ disease ■ Treatment • Treat the hypertension • Ophthalmologic referral ■ Pearl The only pathognomonic funduscopic change of hypertension is focal arteriolar narrowing due to spasm, and it is typically seen in hypertensive crisis. Reference DellaCroce JT, Vitale AT. Hypertension and the eye. Curr Opin Ophthalmol 2008;19:493. [PMID: 18854694] Tell me in a bullet-pointed list what differential diagnoses of Hypertensive Retinopathy are not shared with HIV Retinopathy or with Diabetic Retinopathy.

Your task is to answer questions using information provided in the context block, without referring to external sources or prior knowledge. Format your response using bullet points.

List the reasons that resulted in decreased emission of GHGs from ethanol production.

A new USDA report, titled “A Life-Cycle Analysis of the Greenhouse Gas Emissions of Corn-Based Ethanol,” finds that greenhouse gas (GHG) emissions associated with producing corn-based ethanol in the United States are about 43 percent lower than gasoline when measured on an energy equivalent basis. Unlike other studies of GHG benefits, which relied on forecasts of future ethanol production systems and expected impacts on the farm sector, this study reviewed how the industry and farm sectors have performed over the past decade to assess the current GHG profile of corn-based ethanol. The report shows that the reductions in GHG emissions were driven by a variety of improvements in ethanol production, spanning from the corn field to the ethanol refinery. Farmers are producing corn more efficiently and using conservation practices that reduce GHG emissions, including reduced tillage, cover crops, and improved nitrogen management. Both corn yields and the efficiency of ethanol production technologies are also improving. Previous estimates of ethanol’s GHG balance report lower efficiencies, largely due to anticipated conversion of grasslands and forests to commodity production as a result of increased demand for corn used in ethanol production. However, recent studies of international agricultural land use trends show that since 2004, the primary land use change response of the world's farmers to rising commodity prices has been to use available land resources more efficiently rather than to expand the amount of land used for farming.

A new USDA report, titled “A Life-Cycle Analysis of the Greenhouse Gas Emissions of Corn-Based Ethanol,” finds that greenhouse gas (GHG) emissions associated with producing corn-based ethanol in the United States are about 43 percent lower than gasoline when measured on an energy equivalent basis. Unlike other studies of GHG benefits, which relied on forecasts of future ethanol production systems and expected impacts on the farm sector, this study reviewed how the industry and farm sectors have performed over the past decade to assess the current GHG profile of corn-based ethanol. The report shows that the reductions in GHG emissions were driven by a variety of improvements in ethanol production, spanning from the corn field to the ethanol refinery. Farmers are producing corn more efficiently and using conservation practices that reduce GHG emissions, including reduced tillage, cover crops, and improved nitrogen management. Both corn yields and the efficiency of ethanol production technologies are also improving. Previous estimates of ethanol’s GHG balance report lower efficiencies, largely due to anticipated conversion of grasslands and forests to commodity production as a result of increased demand for corn used in ethanol production. However, recent studies of international agricultural land use trends show that since 2004, the primary land use change response of the world's farmers to rising commodity prices has been to use available land resources more efficiently rather than to expand the amount of land used for farming. Ethanol GHG Balance Highlights  Ethanol production in the United States increased significantly over the past decade—from 3.9 to 14.8 billion gallons per year between 2005 and 2015.  The report projects that the GHG profile of corn ethanol will be almost 50 percent lower than gasoline in 2022 if current trends in corn yields, process fuel switching, and improvements in trucking fuel efficiency continue.  If additional conservation practices and efficiency improvements are pursued, such as the practices outlined in USDA’s Building Blocks for Climate Smart Agriculture and Forestry strategy, the GHG benefits of corn ethanol are even more pronounced over gasoline—about 76 percent.  On-farm conservation practices, such as reduced tillage, cover crops, and nitrogen management, are estimated to improve the GHG balance of corn ethanol by about 14 percent Your task is to answer questions using information provided in the above text, without referring to external sources or prior knowledge. Format your response using bullet points. Question: List the reasons that resulted in decreased emission of GHGs from ethanol production.

When responding, restrict yourself to only information found within the given article - no other information is valid or necessary.

What are the current therapy practices to treat fibromyalgia according to the document?

International Journal of Molecular Sciences Review Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies Massimo E. Ma↵ei Department of Life Sciences and Systems Biology, University of Turin, 10135 Turin, Italy; massimo.ma↵[email protected]; Tel.: +39-011-670-5967 !"#!$%&'(! Received: 6 October 2020; Accepted: 22 October 2020; Published: 23 October 2020 !"#$%&' Abstract: Fibromyalgia (FM) is a syndrome that does not present a well-defined underlying organic disease. FM is a condition which has been associated with diseases such as infections, diabetes, psychiatric or neurological disorders, rheumatic pathologies, and is a disorder that rather than diagnosis of exclusion requires positive diagnosis. A multidimensional approach is required for the management of FM, including pain management, pharmacological therapies, behavioral therapy, patient education, and exercise. The purpose of this review is to summarize the recent advances in classification criteria and diagnostic criteria for FM as well as to explore pharmacotherapy and the use of alternative therapies including the use of plant bioactive molecules. Keywords: fibromyalgia; diagnosis; pharmacotherapy; alternative therapies; plant extracts; natural products 1. Introduction Fibromyalgia (FM) (earlier considered to be fibrositis, to stress the role of peripheral inflammation in the pathogenesis) is a syndrome that does not present a well-defined underlying organic disease. The primary driver of FM is sensitization, which includes central sensitivity syndromes generally referred to joint sti↵ness, chronic pain at multiple tender points, and systemic symptoms including cognitive dysfunction, sleep disturbances, anxiety, fatigue, and depressive episodes [1,2]. FM is a heterogeneous condition that is often associated to specific diseases such as infections, psychiatric or neurological disorders, diabetes and rheumatic pathologies. FM is more frequent in females, where it causes musculoskeletal pain [3] and a↵ects significantly the quality of life, often requiring an unexpected healthcare e↵ort and consistent social costs [4,5]. Usually, a patient-tailored approach requires a pharmacological treatment by considering the risk-benefit ratio of any medication. Being the third most common diagnosis in rheumatology clinics, FM prevalence within the general population appears to range from 1.3–8% [2]. To date there are no specific tests specific for FM. FM is currently recognized by the widespread pain index (which divides the body into 19 regions and scores how many regions are reported as painful) and a symptom severity score (SSS) that assesses cognitive symptoms, unrefreshing sleep and severity of fatigue [6]. It is not clear what causes FM and diagnosing assist the patients to face polysymptomatic distress, thereby reducing doubt and fear which are main psychological factors contributing to this central amplification mechanism [7]. In this review, an update on diagnosis and therapy of FM is provided along the discussion on the possibility of using pharmacological drugs, bioactive natural substances and alternative therapies to alleviate the symptomatology in combination or as alternative remedies to drugs. Int. J. Mol. Sci. 2020, 21, 7877 2 of 27 2. Diagnosis To date there is still a considerable controversy on the assessment and diagnosis of FM. Despite advances in the understanding of the pathologic process, FM remains undiagnosed in as many as 75% of people with the condition [8]. The first attempt for the FM classification criteria is dated 1990 and is based on studies performed in 16 centers in the U.S.A. and Canada in clinical and academic settings, gathering the both doubters and proponents [9]. Since then, several alternative methods of diagnosis have been proposed. In general, most of the researchers agree on the need to assess multiple domains in FM including pain, sleep, mood, functional status, fatigue, problems with concentration/memory (i.e. dyscognition) and tenderness/sti↵ness [5]. Four core areas were initially assessed: (1) pain intensity, (2) physical functioning, (3) emotional functioning, and (4) overall improvement/well-being [10]. About 70–80% of patients with FM also report having sleep disturbances and fatigue. Depressive symptoms, anxiety and mood states have also been included in FM diagnosis. An impairment in multiple areas of function, especially physical function is often reported by patients with FM [11] with a markedly impaired function and quality of life [8]. Since the late 19900 s, a top priority was the development of new disease-specific measures for each of the relevant domains in FM. Also, much attention was paid to studies supporting the valid use of existing instruments specifically in the context of FM [5]. Later on, in 2010, the tender point count was abandoned and the American College of Rheumatology (ACR) suggested preliminary diagnostic criteria which were considering the number of painful body regions evaluating the presence and severity of fatigue, cognitive difficulty, unrefreshed sleep and the extent of somatic symptoms. The diagnostic criteria are not based on laboratory or radiologic testing to diagnose FM and rely on a 0–12 Symptom Severity Scale (SSS) which is used to quantify FM-type symptom severity [12]. Furthermore, the SSS was proposed to be combined with the Widespread Pain Index (WPI) into a 0–31 Fibromyalgianess Scale (FS) [13]. With a specificity of 96.6% and sensitivity of 91.8%, a score 13 for FS was able to correctly classify 93% of patients identified as having FM based on the 1990 criteria [14]. ACR 2010 criteria were also found to be more sensitive than the ACR 1990 criteria, allowing underdiagnosed FM patients to be correctly identified and giving a treatment opportunity to those who had previously been untreated [15]. It is still unclear whether the diagnosis of FM has the same meaning with respect to severity in primary FM (PFM, a dominant disorder that occurs in the absence of another clinically important and dominant pain disorder) and secondary FM (SFM, which occurs in the presence of another clinically important and dominant medical disorder) [16]. Figure 1 shows the ACR 1990 criteria for the classification of fibromyalgia, whereas Figure 2 shows a graphical representation of the Symptom Severity Scale (SSS) plus the Extent of Somatic Symptoms (ESS). Figure 1. Widespread Pain Index from ACR 1990 criteria for the classification of fibromyalgia and related regions. Int. J. Mol. Sci. 2020, 21, 7877 3 of 27 Figure 2. Symptom Severity scale (SSS) and Extent of Somatic Symptoms (ESS). Table 1 shows a holist approach based on the assumption that a multitude of potential diagnoses is fundamental in order to avoid an FM misdiagnosis [17]. In 2013, alternative diagnostic criteria have been developed by some clinicians in the USA including more pain locations and a large range of symptoms than ACR 2010. A self-reported survey was composed of the 28-area pain location inventory and the 10 symptom items from the Symptom Impact Questionnaire (SIQ) [18]. However, when compared to the early 2010 criteria, these alternative criteria did not significantly contribute in di↵erentiating common chronic pain disorders from FM [1]. In 2015, the view of diagnostic criteria was altered by ACR by providing approval only for classification criteria and no longer considering endorsement of diagnostic criteria, stressing that diagnostic criteria are di↵erent from classification criteria and are beyond the remit of the ACR [19]. However, the suggestion that diagnostic and classification criteria represent 2 ends of a continuum implies that the continuum represents the accuracy of the criteria [20]. Classification criteria and diagnostic criteria could intersect; however, according to some authors the terms “diagnosis” and “classification criteria” should be considered as qualitatively distinct concepts. The proposed concept of “diagnostic criteria” [19] is challenging and may be hardly realizable, while diagnostic guidelines based on proper modelling techniques may be helpful for clinicians in particular settings [20]. In 2016, based on a generalized pain criterion and clinic usage data, a new revision of the 2010/2011 FM criteria was developed including the following criteria: 1) generalized pain, defined as pain present in at least 4 of 5 regions; 2) symptoms present at a similar level for at least three months; 3) a WPI 7 and SSS 5 or WPI of 4–6 and SSS 9; 4) a diagnosis of FM is valid irrespective of other diagnoses. Another important point is that the presence of other clinically important illnesses does not exclude a diagnosis of FM [21]. In 2018, considering important but less visible factors that have a profound influence on under- or over-diagnosis of FM provided a new gate to a holistic and real understanding of FM diagnosis, beyond existing arbitrary and constructional scores [22]. Int. J. Mol. Sci. 2020, 21, 7877 4 of 27 Table 1. ACR2010 and modified criteria for the diagnosis of fibromyalgia. Widespread pain index (WPI) Areas specification Number of areas in which the patient has had 0–19 points pain over the past week shoulder girdle, hip (buttock, trochanter), jaw, upper back, lower back, upper arm, upper leg, chest, neck, abdomen, lower arm, Areas to be considered and lower leg (all these areas should be considered bilaterally) Symptom Severity Scale (SSS) score Symptom Level of severity Symptom level Score For each of these 3 symptoms, indicate the level of severity over the past week Considering somatic symptoms in using the following scale: Fatigue general, indicate whether the patient has 0 = no problem Waking unrefreshed the following: 1 = slight or mild problems, generally Cognitive symptoms (e.g., working memory 0 = no symptoms Final score between 0 and 12 mild or intermittent capacity, recognition memory, verbal knowledge, 1 = few symptoms 2 = moderate; considerable problems, anxiety, and depression) 2 = a moderate number of symptoms often present and/or at a moderate level 3 = a great deal of symptoms 3 = severe; pervasive, continuous, life-disturbing problems Criteria Specification Conditions A patient satisfies diagnostic criteria for (a)WPI 7/19 and SS scale score 5 or WPI 3–6 and SS scale score 9 fibromyalgia if the following 3 conditions (b) symptoms have been present as a similar level for at least 3 months are met (c) the patient does not have a disorder that would otherwise explain the pain Modified criteria Specification Conditions Final Score (a)WPI (as above) A patient satisfies diagnostic criteria for (b) SS scale score (as above, but without The number of pain sites (WPI), the SS scale score, and the presence of associated fibromyalgia if the following 3 conditions extent of somatic symptoms) symptoms are summed to give a final score between 0 and 31 are met (c) presence of abdominal pain, depression, headaches (yes = 1, no = 0) Int. J. Mol. Sci. 2020, 21, 7877 5 of 27 In 2019, in cooperation with the WHO, an IASP Working Group has developed a classification system included in the International Classification of Diseases (ICD-11) where FM has been classified as chronic primary pain, to distinguish it from pain which is secondary to an underlying disease [23]. More recently, a study of about 500 patients under diagnosis of FM, revealed that 24.3% satisfied the FM criteria, while 20.9% received a clinician International Classification of Diseases (ICD) diagnosis of FM, with a 79.2% agreement between clinicians and criteria. The conclusions of this study pointed out a disagreement between ICD clinical diagnosis and criteria-based diagnosis of FM, calling into question meaning of a FM diagnosis, the validity of physician diagnosis and clinician bias [24]. FM is a disorder that cannot be based on diagnosis of exclusion, rather needing positive diagnosis [6], through a multidimensional FM diagnostic approach making diagnosis encompassing psychosocial stressors, subjective belief, psychological factors and somatic complaints [25]. The advent of the PSD scale identified a number of problems in FM research [16]. Recently, immunophenotyping analysis performed on blood samples of FM patients revealed a role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM [26]. Moreover, a rapid biomarker-based method for diagnosing FM has been developed by using vibrational spectroscopy to di↵erentiate patients with FM from those with other pain-related diseases. Unique IR and Raman spectral signatures were correlated with FM pain severity measured with FM impact questionnaire revised version (FIQR) [27]. Overall, these findings provide reliable diagnostic tests for di↵erentiating FM from other disorders, for establishing serologic biomarkers of FM-associated pain and were useful for the contribution of the legitimacy of FM as a truly painful disease. In summarizing aspects of FM learned through applications of criteria to patients and trials, Wolfe [28] identified 7 main concepts: 1) there is no way of objectively testing FM which also has no binding definition; 2) prevalence and acceptance of FM depend on factors largely external to the patient; 3) FM is a continuum and not a categorical disorder; 4) every feeling, symptom, physical finding, neuroscience measure, cost and outcome tells one very little about the disorder and its mechanisms when fibromyalgia to “normal subjects” is compared; 5) the range and content of symptoms might indicate that FM may not truly be a syndrome; 6) “pain and distress” type of FM subject identified in the general population [29] might be considered as part of the FM definition and; 7) caution is needed when accepting the current reductive neurobiological causal explanations as sufficient, since FM is a socially constructed and arbitrarily defined and diagnosed dimensional disorder. 3. Therapy 3.1. Pharmacotherapy of FM Clinical trials have failed to conclusively provide overall benefits of specific therapies to treat FM; therefore, current pharmacological treatments for patients su↵ering from FM are mainly directed to palliate some symptoms, with relevant clinical benefits experienced only by a minority of individuals from any one intervention. In those treated with pharmacotherapy, a 50%reduction in pain intensity is generally achieved only by 10% to 25% [30] However, some treatments seem to significantly improve the quality of life of certain FM patients [31]. Only a few drugs have been approved for use in the treatment of FM by the US FDA, whereas no drug has been approved for this indication by the European Medicines Agency. Thus patients with FM frequently need to be treated on an o↵-label basis [32]. Currently, only 25% to 40% pain reduction is granted by drugs and meaningful relief occurs in only 40% to 60%, in part due to dose-limiting adverse e↵ects and incomplete drug efficacy [33]. These limitations in clinical practice have led some to hypothesize that a combination of di↵erent analgesic drugs acting through di↵erent mechanisms may provide superior outcomes compared to monotherapy [34]. Moreover, drugs should be started at low doses and cautiously increased because some patients, either do not tolerate or benefit from drug therapy. Because sleep disturbance, pain and psychological distress are the most amenable to drug therapy, drugs should be chosen to manage the individual’s predominant symptoms [35]. Currently, several drugs are frequently used alone Int. J. Mol. Sci. 2020, 21, 7877 6 of 27 or in combination to manage FM symptoms; however, the US FDA indicated for FM only three: two selective serotonin and norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, and an anticonvulsant, pregabalin [36]. In the next sections, the use of selected drugs aimed to alleviate FM will be described. 3.1.1. Cannabinoids in FM Therapy The cannabinoid system is ubiquitous in the animal kingdom and plays multiple functions with stabilizing e↵ects for the organism, including modulation of pain and stress, and the management of FM may have therapeutic potential by manipulating this system. The cannabinoid system contributes in maintaining equilibrium and stabilizing e↵ects on FM [37]. Moreover, the endocannabinoid neuromodulatory system is involved in multiple physiological functions, such as inflammation and immune recognition, endocrine function, cognition and memory, nausea, antinociception and vomiting, [38]. Deficiency in the endocannabinoid system has been correlated to FM [39], but without clear clinical evidence in support of this assumption [40]. The endocannabinoid system consists of two cannabinoid receptors, the CB1 and CB2 receptors [41]. In acute and chronic pain models, analgesic e↵ects are associated to CB1 agonists that act at many sites along pain transmission pathways, including activation of spinal, supraspinal and peripheral CB1 receptors, each independently decreasing nociception [42]. Delta 9-tetrahydrocannabinol (D9-THC or Dronabinol, 1) is the main active constituent of Cannabis sativa var indica, with psychoactive and pain-relieving properties. The non-selective binding to G-protein-coupled CB receptors is responsible for the pharmacological e↵ects induced by D9-THC. Cannabidiol (CBD, 2), a non-psychotropic constituent of cannabis, is a high potency antagonist of CB receptor agonists and an inverse agonist at the CB2 receptor [43]. CBD displays CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor [44]. This CB2 receptor inverse agonist ability of CBD may contribute to its documented anti-inflammatory properties [44]. The main endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA, 3) and 2-arachidonoylglycerol (2-AG, 4), AG), the activity of which is modulated by the hydrolyzing fatty acid palmitoylethanolamide (PEA, 5) and the endocannabinoid precursor arachidonic acid (AA, 6) [45]. AEA and 2-AG are functionally related to D9-THC [46]. It was found that stress induces a rapid anandamide release in several CNS regions resulting in stress-induced analgesia via CB1 receptors [47]. FM patients had significantly higher anandamide plasma levels [39,46]; however, it has been suggested that the origin of FM and chronic pain depend on a deficiency in the endocannabinoid signaling [45]. Monotherapies of FM based on D9-THC are based on the assumption that this compound acts as an analgesic drug; however, although a sub-population of FM patients reported significant benefits from the use of D9-THC, this statement cannot be made [48]. When the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users, a significant improvement of symptoms of FM in patients using cannabis was observed, although there was a variability of patterns [49]. The synthetic cannabinoid nabilone (7) showed of a superiority over placebo to reduce FM symptoms, with significant reductions in Visual Analog Scale (VAS) for pain, FM Impact Questionnaire (FIQ), and anxiety [42], indicating the efficacy of treating people with FM with nabilone. Nabilone was also e↵ective in improving sleep [50]; however, participants taking nabilone experienced more adverse events (such as dizziness/drowsiness, dry mouth and vertigo) than did participants taking placebo or amitriptyline (see below). The self-medication practice of herbal cannabis was associated with negative psychosocial parameters. Therefore, caution should be exercised in recommending the use of cannabinoids pending clarification of general health and psychosocial problems [51,52]. Figure 3 illustrates the chemical formulas of some cannabinoids and endocannabinoids. Int. J. Mol. Sci. 2020, 21, 7877 7 of 27 Figure 3. Structure formulae of some cannabinoids and related compounds. Numbers correspond to compound names cited in the text. 3.1.2. Opioids in FM Therapy One of the major natural sources of opioids is the medicinal plant Papaver somniferum. Although clinical evidence demonstrating the efficacy or e↵ectiveness of opioids analgesics is scanty, these molecules are widely used for the treatment of FM [53]. However, the long-term use of opioids in FM has been discouraged by several medical guidelines [54]. The use of opioids is documented in studies demonstrating increased endogenous opioid levels in the cerebrospinal fluid of patients with FM vs. controls [55]. These results prompted the interesting hypothesis that a more activated opioid system can be detected in individuals with FM, reflecting reduced receptor availability and increased release of endogenous opioids [54]. There is evidence from both single center, prospective, longitudinal and multicenter and observational clinical studies of negative e↵ects of the use of opioids in FM on patient outcomes compared with other therapies [56,57]. Moreover, opioid user groups showed less improvement in the SFM-36 subscale scores of general health perception and in the FIQ subscale scores of job ability, fatigue and physical impairment [58]. Furthermore, altered endogenous opioid analgesic activity in FM has been demonstrated and suggested as a possible reason for why exogenous opiates appear to have reduced efficacy [59]. Despite these facts, opioids have been prescribed for 10% to 60% of patients with FM as reported in large database sets [54]. When considered, the preference of patients appears towards opioids. In a survey, 75% of patients considered hydrocodone (8) plus acetaminophen to be helpful, and 67% considered oxycodone (9) plus acetaminophen to be helpful [60]. FM has been associated with preoperative opioid use, including hydrocodone [61], whereas there is limited information from randomized controlled trials on the benefits or harms of oxycodone when used to treat pain in FM [62]. A pilot study showed that naltrexone (10) reduced self-reported symptoms of FM (primarily daily pain and fatigue) [63] and further studies showed that low-dose naltrexone had a specific and clinically beneficial impact on FM. This opioid, which is widely available and inexpensive, Int. J. Mol. Sci. 2020, 21, 7877 8 of 27 was found to be safe and well-tolerated. Blocking peripheral opioid receptors with naloxone (11) was observed to prevent acute and chronic training-induced analgesia in a rat model of FM [64]; however, there were no significant e↵ects of naloxone nor nocebo on pressure pain threshold, deep tissue pain, temporal summation or conditioned pain modulation in chronic fatigue syndrome/FM patients [65]. A synthetic opioid receptor agonist that shows serotonin-norepinephrine reuptake inhibitor properties is tramadol (12); this compound is often prescribed for painful conditions [66]. Tramadol has been studied in humans who su↵er from FM [56], suggesting that tramadol may be e↵ective in treating FM [67]. The use of tramadol provides change in pain assessed by visual analogue scale and FM impact questionnaire; however, the reported side e↵ects include dizziness, headache, constipation, addiction, withdrawal, nausea, serotonin syndrome, somnolence, pruritus seizures, drug–drug interactions with antimigraine and antidepressants medications [66]. Therefore, it is recommended that tramadol application should be considered in refractory and more treatment-resistant cases of FM. Another weak opioid is codeine (13). In a comparative study, there was a significantly higher proportion of patients in the codeine-acetaminophen group reporting somnolence or constipation and a larger proportion of patients in the tramadol-acetaminophen group reporting headache. The overall results suggested that tramadol-acetaminophen tablets (37.5 mg/325 mg) were as e↵ective as codeine-acetaminophen capsules (30 mg/300 mg) in the treatment of chronic pain [68]. Fentanyl (14) works primarily by activating µ-opioid receptors and was found to be around 100 times stronger than morphine (15), although its e↵ects are more localized. Fentanyl injections reduced second pain from repeated heat taps in FM patients. Similar to reports of e↵ects of morphine on first and second pain, fentanyl had larger inhibitory e↵ects on slow temporal summation of second pain than on first pain from a nociceptor stimulation [69]. Since fentanyl can inhibit windup of second pain in FM patients, it can prevent the occurrence of intense summated second pain and thereby reduce its intensity by a greater extent than first or second pains evoked by single stimuli. Among the 70,237 drug-related deaths estimated in 2017 in the US, the sharpest increase occurred among those related to fentanyl analogs with almost 29,000 overdose deaths which represents more than 45% increase from 2016 to 2017 [70]. Because the numbers of overdoses and deaths due to fentanyl will continue to increase in the coming years, studies are needed to elucidate the physiological mechanisms underlying fentanyl overdose in order to develop e↵ective treatments aimed to reduce the risk of death [71]. Glial cell activation is one of the several other possible pathophysiologic mechanisms underlying the development of FM by contributing to central nervous system sensitization to nociceptive stimuli [72]. Pentoxifylline (16), a xanthine derivative used as a drug to treat muscle pain in people with peripheral artery disease, is a nonspecific cytokine inhibitor that has been shown to attenuate glial cell activation and to inhibit the synthesis of TNF↵, IL-1 , and IL-6 [73]. In theory, attenuating glial cell activation via the administration of pentoxifylline to individuals su↵ering from FM might be efficient in ameliorating their symptoms without being a globalist therapeutic approach targeting all possible pathophysiologic mechanisms of development of the syndrome [74]. With regards FM pathophysiology, serum brain-derived neurotrophic factors (BDNF) were found at higher levels in FM patients while BDNF methylation in exon 9 accounted for the regulation of protein expression. These data suggest that altered BDNF levels might represent a key mechanism explaining FM pathophysiology [75]. Opioid users were also observed to experience a decreased pain and symptom severity when ca↵eine (17) was consumed, but this was not observed in opioid nonusers, indicating ca↵eine may act as an opioid adjuvant in FM-like chronic pain patients. Therefore the consumption of ca↵eine along with the use of opioid analgesics could represent an alternative therapy with respect to opioids or ca↵eine alone [76]. Figure 4 shows the chemical formulae of some opioids used in FM therapy. Int. J. Mol. Sci. 2020, 21, 7877 9 of 27 Figure 4. Structure formulae of some opioids and related compounds. Numbers correspond to molecules cited in the text. 3.1.3. Gabapentinoids in FM Therapy Gabapentinoid drugs are US Food and Drug Administration (FDA) (but not in Europe) anticonvulsants approved for treatment of pain syndromes, including FM. However, FDA approved pregabalin (18) but not gabapentin (19) for FM treatment; nevertheless, gabapentin is often prescribed o↵-label for FM, presumably because it is substantially less expensive [77]. Pregabalin is a gamma-aminobutyric acid (GABA) analog and is a ligand for the ↵2 subunit of the calcium channel being able of reducing the ability of docked vesicles to fuse and release neurotransmitters [78]. Pregabalin shows e↵ects on cortical neural networks, particularly when basal neurons are under hyperexcitability. The pain measures and pregabalin impact on the cortical excitability was observed only in FM patients [79]. Pregabalin was also found to increase norepinephrine levels in reserpine-induced myalgia rats [80]. Because of its tolerability when used in combination with antidepressants, pregabalin use showed a very good benefit to risk ratio [81]. The starting approved dosage for pregabalin is at 150 mg daily [82]; however, the drug shows a higher e↵ectiveness when used at a dose of 300 or 600 mg/day. Lower pregabalin doses than those of clinical trials are used in clinical practice because higher doses are more likely to be intolerable [83]. A recent systematic review shows that a minority of people with moderate to severe pain due to FM treated with a daily dose of 300 to 600 mg of pregabalin had a reduction of pain intensity over a follow-up period of 12 to 26 weeks, with tolerable adverse e↵ects [84]. Thus, pregabalin is one of cardinal drugs used in the treatment of FM, and its clinical utility has been comprehensively demonstrated [85,86]. Nevertheless, there is still insufficient evidence to support or refute that gabapentin may reduce pain in FM [87]. Figure 5 depicts the chemical formulae of some gabapentinoids. Int. J. Mol. Sci. 2020, 21, 7877 10 of 27 Figure 5. Structure formulae of some gabapentinoids. Numbers correspond to molecules cited in the text. 3.1.4. Serotonin–Norepinephrine Reuptake Inhibitors in FM Therapy There is a wide use of serotonin and noradrenaline reuptake inhibitors (SNRIs). There is no unbiased evidence that serotonin selective reuptake inhibitors (SSRIs) are superior to placebo in treating depression in people with FM and for treating the key symptoms of FM, namely sleep problems, fatigue and pain. However, it should be considered that young adults aged 18 to 24, with major depressive disorder, showed an increased suicidal tendency when treated with SSRIs [88]. A recent Cochrane review evaluated the use of SNRIs including eighteen studies with a total of 7,903 adults diagnosed with FM, by using desvenlafaxine (20) and venlafaxine (21) in addition to duloxetine (22) and milnacipran (23), by considering various outcomes for SNRIs including health related quality of life, fatigue, sleep problems, pain and patient general impression, as well as safety and tolerability [89]. Fifty two percent of those receiving duloxetine and milnacipran had a clinically relevant benefit over placebo compared to 29% of those on placebo, with much or very much improvements in the intervention. On the other hand, reduction of pain intensity was not significantly di↵erent from placebo when desvenlafaxine was used. However, pain relief and reduction of fatigue was not clinically relevant for duloxetine and milnacipran in 50% or greater and did not improve the quality of life [90]. Same negative outcomes were found for reducing problems in sleep and the potential general benefits of duloxetine and milnacipran were outweighed by their potential harms. The efficacy of venlafaxine in the treatment of FM was studied to a lesser extent. The lack of consistency in venlafaxine dosing, placebo control and blinding make difficult to understand whether the molecule is e↵ective in treating FM. Nevertheless, tolerability and the lower cost of venlafaxine increases its potential use for the treatment of FM, by rendering the molecule a more a↵ordable option compared to the other, more expensive SNRIs [91]. Mirtazapine (24) promotes the release of noradrenaline and serotonin by blocking ↵2 -adrenergic autoreceptors and ↵2 -adrenergic heteroreceptors, respectively. Mirtazapine, by acting through 5-HT1A receptors and by blocking postsynaptic 5-HT2A , 5-HT2C , and 5-HT3 receptors is able to enhance serotonin neurotransmission [92]. For these properties, mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant [93]. Mirtazapine appears to be a promising therapy to improve sleep, pain, and quality of life in patients with FM [94]. In Japanese patients with FM, mirtazapine caused a significantly greater reduction in the mean numerical rating scale pain score and remained significantly greater from week 6 onward, compared with placebo. However, Adverse mirtazapine caused adverse events including weight gain, somnolence and increased appetite when compared to placebo [92]. Among antidepressants, the tricyclic antidepressant (TCAs) amitriptyline (25) was studied more than other antidepressants. It is frequently used to assess comparative efficacy [95] and for many years amitriptyline has been a first-line treatment for FM. Although there is no supportive unbiased evidence for a beneficial e↵ect, the drug was successful for the treatment in many patients with FM. However, amitriptyline achieve satisfactory pain relief only by a minority of FM patients and is unlikely that any large randomized trials of amitriptyline will be conducted in FM to establish efficacy Int. J. Mol. Sci. 2020, 21, 7877 11 of 27 statistically, or measure the size of the e↵ect [96]. Figure 6 depicts the chemical formulae of some SNRIs and TCA. Figure 6. Chemical structure of some serotonin and noradrenaline reuptake inhibitors and a tricyclic antidepressant. Numbers correspond to molecules cited in the text. 3.2. Alternative Therapies for FM A survey of the European guidelines shows that most of the pharmacological therapies are relatively modest providing only weak recommendations for FM [97]. A multidimensional approach is therefore required for the management of FM, including pharmacological therapies along with behavioral therapy, exercise, patient education and pain management. A multidisciplinary approach combines pharmacotherapy with physical or cognitive interventions and natural remedies. Very often, patients seek help in alternative therapies due to the limited efficacy of the therapeutic options. The following sections discuss some of the most used alternative therapies to treat FM. 3.2.1. Acupunture Acupuncture shows low to moderate-level in improving pain and sti↵ness in people with FM. In some cases, acupuncture does not di↵er from sham acupuncture in improving sleep or global well-being or reducing pain or fatigue. The mechanisms of acupuncture action in FM treatment appears to be correlated to changes in serum serotonin levels [98]. Electro-acupuncture (EA) was more e↵ective than manual acupuncture (MA) for improving sleep, global well-being and fatigue and in the reduction of pain and sti↵ness. Although e↵ective, the e↵ect of acupuncture is not maintained at six months follow-up [99]. Moreover, there is a lack of evidence that real acupuncture significantly di↵ers from sham acupuncture with respect to improving the quality of life, both in the short and long term. However, acupuncture therapy is a safe treatment for patients with FM [100,101]. 3.2.2. Electric Stimulation As we discussed, FM, aside pain, is characterized by anxiety, depression and sleep disturbances, and by a complex cognitive dysfunctioning status known as “fibrofog” which is characterized by disturbance in working memory, attention and executive functions globally often referred by the patients as a sense of slowing down, clumsiness and confusion that have a profound impact on the ability to perform and e↵ectively plan daily activities [102,103]. Besides stimulation with acupuncture, the e↵ective modulation of brain areas has been obtained through non-invasive brain stimulation by Int. J. Mol. Sci. 2020, 21, 7877 12 of 27 magnetic or electric currents applied to the scalp like transcranial magnetic and electrical stimulation. In many cases, to relieve pain and improve general FM-related function, the use of anodal transcranial direct current stimulation over the primary motor cortex was found to be significantly more e↵ective than sham transcranial direct current stimulation [104]. If we consider that pharmacological and non-pharmacological treatments are often ine↵ective or transitory in their e↵ect on FM, therapeutic electrical stimulation appears to have a potential role [105]. Cognitive functions such as memory have been enhanced in FM patients by anodal transcranial direct current stimulation over the dorsolateral prefrontal cortex and has clinical relevance for top-down treatment approaches in FM [106]. In FM patients, modulation of hemodynamic responses by transcutaneous electrical nerve stimulation during delivery of nociceptive stimulation was also investigated and shown to be an e↵ective factor in FM treatment, although the underlying mechanism for these findings still needs to be clarified [107]. It has been recently demonstrated that both transcutaneous electric nerve stimulation and acupuncture applications seem to be beneficial in FM patients [108]. In a recent Positron Emission Tomography H2 15 O activation study it was shown that occipital nerve field stimulation acts through activation of the descending pain inhibitory pathway and the lateral pain pathway in FM, while electroencephalogram shows activation of those cortical areas that could be responsible for descending inhibition system recruitment [109]. Microcirculation is of great concern in patients with FM. Recently low-energy pulsed electromagnetic field therapy was found to increase a promising therapy to increase microcirlulation [110]; however, neither pain and sti↵ness were reduced nor functioning was improved by this therapy in women with FM [111]. The European Academy of Neurology, based on the method of GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) judged anodal transcranial direct currents stimulation of motor cortex as still inconclusive for treatment of FM [112]. Therefore, further studies are needed to determine optimal treatment protocols and to elucidate the mechanisms involved [113]. 3.2.3. Vibroacoustic and Rhythmic Sensory Stimulation Stimulation with sensory events such as pulsed or continuous auditory, vibrotactile and visual flickering stimuli are referred as rhythmic sensory stimulation [114]. Clinical studies have reported the application of vibroacoustic stimulation in the treatment of FM. In a clinal study, one group of patients with FM listened to a sequence of Bach’s compositions, another was subjected to vibratory stimuli on a combination of acupuncture points on the skin and a third group received no stimulation. The results showed that a greater e↵ect on FM symptoms was achieved by the combined use of music and vibration [115]. However, in another study, neither music nor musically fluctuating vibration had a significant e↵ect on tender point pain in FM patients when compared to placebo treatment [116]. Because thalamocortical dysrhythmia is implicated in FM and that low-frequency sound stimulation can play a regulatory function by driving neural rhythmic oscillatory activity, volunteers with FM were subjected to 23 min of low-frequency sound stimulation at 40 Hz, delivered using transducers in a supine position. Although no adverse e↵ects in patients receiving the treatment, no statistically and clinically relevant improvement were observed [117]. On the other hand, gamma-frequency rhythmic vibroacoustic stimulation was found to decrease FM symptoms (depression, sleep quality and pain interference) and ease associated comorbidities (depression and sleep disturbances), opening new avenues for further investigation of the e↵ects of rhythmic sensory stimulation on chronic pain conditions [118]. 3.2.4. Thermal Therapies Thermal therapies have been used to treat FM. Two main therapies are currently used: body warming and cryotherapy. Int. J. Mol. Sci. 2020, 21, 7877 13 of 27 Because FM is strongly linked to rheumatic aches, the application of heat by spa therapy (balneotherapy) appears as a natural choice for the treatment of FM [119]. Spa therapy is a popular treatment for FM in many European countries, as well as in Japan and Israel. A randomized prospective study of a 10-day treatment was done on 48 FM patients improving their quality of life [120] and showed that treatment of FM at the Dead Sea was both e↵ective and safe [121]. FM patients who were poorly responding to pharmacological therapies were subjected to mud-bath treatment. A cycle of mud bath applications showed beneficial e↵ects on FM patients whose evaluation parameters remained stable after 16 weeks in comparison to baseline [122]. In patients su↵ering from FM, mud bathing was also found to prevent muscle atrophy and inflammation and improve nutritional condition [123]. Nevertheless, despite positive results, the methodological limitations of available clinical studies, such as the lack of placebo double-blinded trials, preclude definitive conclusions on the e↵ect of body-warming therapies to treat FM [119,124]. A remedy widely used in sports related trauma is the application of cold as a therapeutic agent for pain relief. Cryotherapy refers to the use of low temperatures to decrease the inflammatory reaction, including oedema [125]. Cryotherapy induces several organism physiological reactions like increasing anti-inflammatory cytokines, beta-endorphins, ACTH, white blood cells, catecholamines and cortisol, immunostimulation due to noradrenalin response to cold, the increase in the level of plasma total antioxidant status and the reduction of pain through the alteration of nerve conduction [126]. When compared to control FM subjects, cryotherapy-treated FM patients reported a more pronounced improvement of the quality of life [127]. Whole body cryotherapy was also found to be a useful adjuvant therapy for FM [126]. 3.2.5. Hyperbaric Treatment Hyperbaric oxygen therapy (HBOT) has shown beneficial e↵ects for the prevention and treatment of pain [128], including migraine, cluster headache [129] and FM [130]. HBOT is supposed to induce neuroplasticity that leads to repair of chronically impaired brain functions. HBOT was also found to it improve the quality of life in post-stroke patients and mild traumatic brain injury patients [131]. Therefore, the increased oxygen concentration caused by HBOT is supposed to change the brain metabolism and glial function with a potential e↵ect on reducing the FM-associated brain abnormal activity [132]. HBOT was found to a↵ect the mitochondrial mechanisms resulting in functional brain changes, stimulate nitric oxide production thus alleviating hyperalgesia and promoting the NO-dependent release of endogenous opioids which appear to be involved in the antinociception prompted by HBOT [133]. In a clinical study, a significant di↵erence between the HBOT and control groups was found in the reduction in tender points and VAS scores after the first and fifteenth therapy sessions [130]. These results indicate that HBOT may play an important role in managing FM. 3.2.6. Laser Therapy and Phototherapy The use of di↵erent light wavelengths has been found to be an alternative therapy for FM. It is known that low-level laser therapy is a therapeutic factor, being able not only to target one event in the painful reception, but rather the extend its e↵ectiveness on the whole hierarchy of mechanisms of its origin and regulation [134]. Laser photobiomodulation therapy has been reported to be e↵ective in the treatment of a variety of myofascial musculoskeletal disorders, including FM [135]. The combination of laser therapy and the administration of the drug amitriptyline was found to be e↵ective on clinical symptoms and quality of life in FM; furthermore, gallium-arsenide laser therapy was found to be a safe and e↵ective treatment which can be used as a monotherapy or as a supplementary treatment to other therapeutic procedures in FM [136]. Evidence supported also the use of laser therapy in women su↵ering FM to improve pain and upper body range of motion, ultimately reducing the impact of FM [137,138]. Finally, a combination of phototherapy and exercise training was evaluated in patients with FM in a randomized controlled trial for chronic pain to o↵er valuable clinical evidence for objective assessment of the potential benefits and risks of procedures [139]. Int. J. Mol. Sci. 2020, 21, 7877 14 of 27 3.2.7. Exercise and Massage Exercise therapy seems to be an e↵ective component of treatment, yielding improvement in pain and other symptoms, as well as decreasing the burden of FM on the quality of life [140]. Exercise is generally acceptable by individuals with FM and was found to improve the ability to do daily activities and the quality of life and to decrease tiredness and pain [141]. However, it is important to know the e↵ects and specificities of di↵erent types of exercise. For instance, two or more types of exercise may combine strengthening, aerobic or stretching exercise; however, there is no substantial evidence that mixed exercise may improve sti↵ness [142]. Quality of life may be improved by muscle stretching exercise, especially with regard to physical functioning and pain, whereas depression is reduced by resistance training. A trial including a control group and two intervention groups, both of which receiving exercise programs created specifically for patients with FM, showed that both modalities were e↵ective in an exercise therapy program for FM [143]. A progressive muscle strengthening activity was also found to be a safe and e↵ective mode of exercise for FM patients [144]. Furthermore, strength and flexibility exercises in aerobic exercise rehabilitation for FM patients led to improvements in patients’ shoulder/hip range of motion and handgrip strength [145]. Among women with FM, the association between physical activity and daily function is mediated by the intensity of musculoskeletal pain, rather than depressive symptoms or body mass [146], with a link between clinical and experimental pain relief after the performance of isometric contractions [147]. A randomized controlled trial evaluated the e↵ects of yoga intervention on FM symptoms. Women performing yoga showed a significant improvement on standardized measures of FM symptoms and functioning, including fatigue, mood and pain, and in pain acceptance and other coping strategies [148]. Moreover, the combination with massage therapy program during three months influenced perceived stress index, cortisol concentrations, intensity of pain and quality of life of patients with FM [149]. In terms of societal costs and health care costs, quality of life and physical fitness in females with FM was improved by aquatic training and subsequent detraining [150,151]. Aquatic physical training was e↵ective in promoting increased oxygen uptake at peak cardiopulmonary exercise test in women with FM [152]. A systematic evaluation of the harms and benefits of aquatic exercise training in adults with FM showed that it may be beneficial for improving wellness, symptoms, and fitness in adults with FM [153,154]. A safe and clinically efficacious treatment of pain and other FM symptoms was also achieved by the combination of osteopathic manipulative medicine and pharmacologic treatment with gabapentin [155]. Dancing is a type of aerobic exercise that may be used in FM alternative therapy. Belly dancing was found to be e↵ective in improving functional capacity, pain, quality of life and improving body image of women with FM [156]. More recently, three months treatment of patients with FM with Zumba dancing was found to be e↵ective in improving pain and physical functioning [157]. Finally, Tai chi mind-body treatment was found to improve FM symptoms as much as aerobic exercise and longer duration of Tai chi showed greater improvement. According to a recent report, mind-body approaches may take part of the multidisciplinary management of FM and be considered an alternative therapeutic option [158]. 3.2.8. Probiotics and FM Therapy A tractable strategy for developing novel therapeutics for complex central nervous system disorders could rely on the so called microbiota-gut-brain axis management, because intestinal homeostasis may directly a↵ect brain functioning [159,160]. The pain intensity of patients with FM has been reported to be correlated with the degree of small intestinal bacterial overgrowth, which is often associated with an increased intestinal permeability whose values were significantly increased in the FM patients [161]. Preclinical trials indicate that the microbiota and its metabolome are likely involved in modulating brain processes and behaviors [162]. Therefore, FM patients should show better performance after the treatment with probiotics. In a double-blind, placebo-controlled, randomized design probiotic Int. J. Mol. Sci. 2020, 21, 7877 15 of 27 improved impulsive choice and decision-making in FM patients, but no other e↵ects were observed on cognition, quality of life, self-reported pain, FM impact, depressive or anxiety symptoms [163]. 3.2.9. Use of Plant Extracts and Natural Products for FM Treatment About 40% of drugs used to treat FM originate from natural products [164]; however, there are a few studies that prove the safe and e↵ective use of various plant extracts in FM therapy. Several plant extracts are currently used for their antinociceptive properties and potential to treat FM [165]. Papaver somniferum is probably the most ancient plant used for its antinociceptive properties [166], with chemical components able to interact with opioid receptors; among these morphine (15) which is not only the oldest, but is still the most e↵ective drug for the management of severe pain in clinical practice [167]. The use of opioids for FM treatment has been discussed above. Another important plant is Cannabis sativa. The major active constituent of Cannabis, D9-THC (1), has been shown to possess antinociceptive properties when assessed in several experimental models [168] (see also the discussion above on cannabinoids). Although there is still scarce evidence to support its role in the treatment of FM, a large consensus indicates that medical cannabis could be an e↵ective alternative for the treatment of FM symptoms [169]. The illicit use of herbal cannabis for FM treatment has been correlated to the inefficacy of current available medications, but is also linked to popular advocacy or familiarity with marijuana from recreational use. Therefore, physicians are requested to examine the global psychosocial well-being, and not focus only on the single outcome measure of pain [52,170]. Although medical cannabis treatment has a significant favorable e↵ect on patients with FM, 30% of patients experience adverse e↵ects [171] and 8% report dependence on cannabis [172]. VAS scores measured in 28 FM patients after 2 hours of cannabis use showed enhancement of relaxation and feeling of well-being, a reduction of pain and sti↵ness which were accompanied by an increase in somnolence. The mental health component summary score of the Short Form 36 Health Survey was higher in cannabis users than in non-users [49]. Among terpenoids, administration of trans- -caryophyllene (BCP, 26), a bicyclic sesquiterpene compound existing in the essential oil of many plants like Copaifera langsdforffii, Cananga odorata, Humulus lupulus, Piper nigrum and Syzygium aromaticum, which provide a high percentage of BCP along with interesting essential oil yields [173], significantly minimized the pain in both acute and chronic pain models [174]. BCP selectively binds to the cannabinoid 2 (CB2 ) receptor and is a functional CB2 agonist. Upon binding to the CB2 receptor, BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes [175]. BCP, a safe compound with toxicity at doses higher than 2000 mg/kg body weight [176], was found to reduce the primary and secondary hyperalgesia produced by a chronic muscle pain model (which is considered to be an animal model for FM) [177]. Significant and dose-dependent antinociceptive response was produced by BCP without the presence of gastric damage [178]. Antiallodynic actions of BCP are exerted only through activation of local peripheral CB2 [179]. In neuropathic pain models, BCP reduced spinal neuroinflammation and the oral administration was more e↵ective than the subcutaneously injected synthetic CB2 agonist JWH-133 [180]. Recently, BCP was found to exert an analgesic e↵ect in an FM animal model through activation of the descending inhibitory pain pathway [181]. Thus, BCP may be highly e↵ective in the treatment of long-lasting, debilitating pain states, suggesting the interesting application of BCP in FM therapy. The analgesic properties of myrrh (Commiphora myrrha) have been known since ancient times and depend on the presence of bioactive sesquiterpenes with furanodiene skeletons which are able to interact with the opioid receptors [182,183]. C. myrrha extracts exerted a stronger suppression on carrageenan-induced mice paw edema with significant analgesic e↵ects [184] and were e↵ective against chronic inflammatory joint disease such as osteoarthritis [185]. In a preclinical trial, pain alleviation was obtained with C. myrrha extracts for many pathologies [186], indicating that extracts from this plant may have the potential to treat FM. Int. J. Mol. Sci. 2020, 21, 7877 16 of 27 Preclinical studies indicate a potential use of Hypericum perforatum (Hypericaceae), popularly known as St. John’s wort, in medical pain management [187] due to its phenolic compounds. Many phenolic compounds (e.g., flavonoids) from medicinal plants are promising candidates for new natural analgesic drugs [188]. Quercetin (27) showed analgesic activity and could reduce neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons of db/db mice [189], while rutin (28) could inhibit the writhing response of mice induced by potassium antimony tartrate and showed to be a promising pharmacological approach to treat pain [190]. The analgesia potency of hyperin (29) was approximately 20-fold of morphine, while luteolin (30) presented e↵ective analgesic activities for both acute and chronic pain management. Some glycosides of kaempferol (e.g., kaempferol 3-O-sophoroside, 31) possess significant analgesic activity in the tail clip, tail flick, tail immersion, and acetic acid-induced writhing models, whereas baicalin (32) shows analgesic e↵ects in several kinds of pain [191]. Fisetin (33), a plant flavonoid polyphenol, has been reported to possess potent antioxidant, antinociceptive and neuroprotective activities. In rats, fisetin acts via modulation of decreased levels of biogenic amines and elevatesoxido-nitrosative stress and ROS to ameliorate allodynia, hyperalgesia, and depression in experimental reserpine-induced FM [192]. In a double-blind parallel-group clinical trial, outpatients with FM were randomized to receive either 15 mg of Crocus sativus (sa↵ron) extract or 30 mg duloxetine (22). No significant di↵erence was detected for any of the scales neither in terms of score changes from baseline to endpoint between the two treatment arms, indicating that sa↵ron and duloxetine had comparable efficacy in treatment of FM symptoms [193]. It is still unclear the efficacy of natural products extracted from plants in treating FM. However, some clinical data show promising results and more studies with adequate methodological quality are necessary in order to investigate the efficacy and safety of natural products as a support in FM therapy. Figure 7 depicts the chemical formulae of some antinociceptive natural products. Figure 7. Chemical structure of some natural compounds with antinociceptive activity. Int. J. Mol. Sci. 2020, 21, 7877 17 of 27 4. Conclusions Diagnosis of FM is based on clinical feature and criteria that still lack either a gold standard or at least supportive laboratory findings. FM diagnostic criteria may include heterogeneous patients also in clinical trials and this may impair evaluation of clinically meaningful treatment e↵ect. The review of the literature suggests that a multidisciplinary therapeutic approach, based on the combination of pharmacologic and alternative therapy (including thermal, light, electrostimulatory and body exercise treatments) could improve the quality of life and reduce pain and other symptoms related to FM. However, sometimes the ability of patients to participate to alternative therapies is impeded by the level of pain fatigue, poor sleep, and cognitive dysfunction. These patients may need to be managed with medications before initiating nonpharmacologic therapies. Although the use of some natural phytochemicals like BCP and phenolic compounds might replace other natural products such as D9-THC, because of reduced side e↵ects and higher tolerability, FM self medication practice may be ine↵ective and in some cases even detrimental. Therefore, providing FM patients with the correct information about their disorders may help monitoring pharmacological and alternative therapies. At the same time maintaining information will help patients to receive the appropriate medications and therapies [194]. Funding: This research received no external funding. Conflicts of Interest: The author declares no conflict of interest Abbreviations 2-AG 2-ArachidonoylGlycerol AA Arachidonic Acid ACR American College of Rheumatology ACTH Adrenocorticotropic hormone AEA N-arachidonoylethanolamine BDNF Brain-Derived Neurotrophic Factors CB1 Cannabinoid Receptor 1 CB2 Cannabinoid Receptor 2 CBD Cannabidiol CNS Central Nervous System EA Electro-Acupuncture ESS Extent of Somatic Symptoms FIQ FM Impact Questionnaire FIQR FM Impact Questionnaire Revised version FM Fibromyalgia FS Fibromyalgianess Scale GABA Gamma-Aminobutyric Acid Grading of Recommendations, Assessment, GRADE Development, and Evaluation HBOT Hyperbaric Oxygen Therapy ICD-11 International Classification of Diseases IL-1 Interleukin 1 beta IL-6 Interleukin 6 MA Manual Acupuncture PEA Palmitoylethanolamide PFM Primary FM ROS Reactive Oxygen Species SIQ Symptom Impact Questionnaire SFM Secondary FM SNRIs Serotonin and Norepinephrine Reuptake Inhibitors SSRIs Serotonin Selective Reuptake Inhibitors SSS Symptom Severity Scale TCAs Tricyclic Antidepressant TNF↵ Tumor necrosis factor alpha VAS Visual Analog Scale WPI Widespread Pain Index D9-THC Delta 9-tetrahydrocannabinol Int. 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When responding, restrict yourself to only information found within the given article - no other information is valid or necessary. What are the current therapy practices to treat fibromyalgia according to the document? International Journal of Molecular Sciences Review Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies Massimo E. Ma↵ei Department of Life Sciences and Systems Biology, University of Turin, 10135 Turin, Italy; massimo.ma↵[email protected]; Tel.: +39-011-670-5967 !"#!$%&'(! Received: 6 October 2020; Accepted: 22 October 2020; Published: 23 October 2020 !"#$%&' Abstract: Fibromyalgia (FM) is a syndrome that does not present a well-defined underlying organic disease. FM is a condition which has been associated with diseases such as infections, diabetes, psychiatric or neurological disorders, rheumatic pathologies, and is a disorder that rather than diagnosis of exclusion requires positive diagnosis. A multidimensional approach is required for the management of FM, including pain management, pharmacological therapies, behavioral therapy, patient education, and exercise. The purpose of this review is to summarize the recent advances in classification criteria and diagnostic criteria for FM as well as to explore pharmacotherapy and the use of alternative therapies including the use of plant bioactive molecules. Keywords: fibromyalgia; diagnosis; pharmacotherapy; alternative therapies; plant extracts; natural products 1. Introduction Fibromyalgia (FM) (earlier considered to be fibrositis, to stress the role of peripheral inflammation in the pathogenesis) is a syndrome that does not present a well-defined underlying organic disease. The primary driver of FM is sensitization, which includes central sensitivity syndromes generally referred to joint sti↵ness, chronic pain at multiple tender points, and systemic symptoms including cognitive dysfunction, sleep disturbances, anxiety, fatigue, and depressive episodes [1,2]. FM is a heterogeneous condition that is often associated to specific diseases such as infections, psychiatric or neurological disorders, diabetes and rheumatic pathologies. FM is more frequent in females, where it causes musculoskeletal pain [3] and a↵ects significantly the quality of life, often requiring an unexpected healthcare e↵ort and consistent social costs [4,5]. Usually, a patient-tailored approach requires a pharmacological treatment by considering the risk-benefit ratio of any medication. Being the third most common diagnosis in rheumatology clinics, FM prevalence within the general population appears to range from 1.3–8% [2]. To date there are no specific tests specific for FM. FM is currently recognized by the widespread pain index (which divides the body into 19 regions and scores how many regions are reported as painful) and a symptom severity score (SSS) that assesses cognitive symptoms, unrefreshing sleep and severity of fatigue [6]. It is not clear what causes FM and diagnosing assist the patients to face polysymptomatic distress, thereby reducing doubt and fear which are main psychological factors contributing to this central amplification mechanism [7]. In this review, an update on diagnosis and therapy of FM is provided along the discussion on the possibility of using pharmacological drugs, bioactive natural substances and alternative therapies to alleviate the symptomatology in combination or as alternative remedies to drugs. Int. J. Mol. Sci. 2020, 21, 7877 2 of 27 2. Diagnosis To date there is still a considerable controversy on the assessment and diagnosis of FM. Despite advances in the understanding of the pathologic process, FM remains undiagnosed in as many as 75% of people with the condition [8]. The first attempt for the FM classification criteria is dated 1990 and is based on studies performed in 16 centers in the U.S.A. and Canada in clinical and academic settings, gathering the both doubters and proponents [9]. Since then, several alternative methods of diagnosis have been proposed. In general, most of the researchers agree on the need to assess multiple domains in FM including pain, sleep, mood, functional status, fatigue, problems with concentration/memory (i.e. dyscognition) and tenderness/sti↵ness [5]. Four core areas were initially assessed: (1) pain intensity, (2) physical functioning, (3) emotional functioning, and (4) overall improvement/well-being [10]. About 70–80% of patients with FM also report having sleep disturbances and fatigue. Depressive symptoms, anxiety and mood states have also been included in FM diagnosis. An impairment in multiple areas of function, especially physical function is often reported by patients with FM [11] with a markedly impaired function and quality of life [8]. Since the late 19900 s, a top priority was the development of new disease-specific measures for each of the relevant domains in FM. Also, much attention was paid to studies supporting the valid use of existing instruments specifically in the context of FM [5]. Later on, in 2010, the tender point count was abandoned and the American College of Rheumatology (ACR) suggested preliminary diagnostic criteria which were considering the number of painful body regions evaluating the presence and severity of fatigue, cognitive difficulty, unrefreshed sleep and the extent of somatic symptoms. The diagnostic criteria are not based on laboratory or radiologic testing to diagnose FM and rely on a 0–12 Symptom Severity Scale (SSS) which is used to quantify FM-type symptom severity [12]. Furthermore, the SSS was proposed to be combined with the Widespread Pain Index (WPI) into a 0–31 Fibromyalgianess Scale (FS) [13]. With a specificity of 96.6% and sensitivity of 91.8%, a score 13 for FS was able to correctly classify 93% of patients identified as having FM based on the 1990 criteria [14]. ACR 2010 criteria were also found to be more sensitive than the ACR 1990 criteria, allowing underdiagnosed FM patients to be correctly identified and giving a treatment opportunity to those who had previously been untreated [15]. It is still unclear whether the diagnosis of FM has the same meaning with respect to severity in primary FM (PFM, a dominant disorder that occurs in the absence of another clinically important and dominant pain disorder) and secondary FM (SFM, which occurs in the presence of another clinically important and dominant medical disorder) [16]. Figure 1 shows the ACR 1990 criteria for the classification of fibromyalgia, whereas Figure 2 shows a graphical representation of the Symptom Severity Scale (SSS) plus the Extent of Somatic Symptoms (ESS). Figure 1. Widespread Pain Index from ACR 1990 criteria for the classification of fibromyalgia and related regions. Int. J. Mol. Sci. 2020, 21, 7877 3 of 27 Figure 2. Symptom Severity scale (SSS) and Extent of Somatic Symptoms (ESS). Table 1 shows a holist approach based on the assumption that a multitude of potential diagnoses is fundamental in order to avoid an FM misdiagnosis [17]. In 2013, alternative diagnostic criteria have been developed by some clinicians in the USA including more pain locations and a large range of symptoms than ACR 2010. A self-reported survey was composed of the 28-area pain location inventory and the 10 symptom items from the Symptom Impact Questionnaire (SIQ) [18]. However, when compared to the early 2010 criteria, these alternative criteria did not significantly contribute in di↵erentiating common chronic pain disorders from FM [1]. In 2015, the view of diagnostic criteria was altered by ACR by providing approval only for classification criteria and no longer considering endorsement of diagnostic criteria, stressing that diagnostic criteria are di↵erent from classification criteria and are beyond the remit of the ACR [19]. However, the suggestion that diagnostic and classification criteria represent 2 ends of a continuum implies that the continuum represents the accuracy of the criteria [20]. Classification criteria and diagnostic criteria could intersect; however, according to some authors the terms “diagnosis” and “classification criteria” should be considered as qualitatively distinct concepts. The proposed concept of “diagnostic criteria” [19] is challenging and may be hardly realizable, while diagnostic guidelines based on proper modelling techniques may be helpful for clinicians in particular settings [20]. In 2016, based on a generalized pain criterion and clinic usage data, a new revision of the 2010/2011 FM criteria was developed including the following criteria: 1) generalized pain, defined as pain present in at least 4 of 5 regions; 2) symptoms present at a similar level for at least three months; 3) a WPI 7 and SSS 5 or WPI of 4–6 and SSS 9; 4) a diagnosis of FM is valid irrespective of other diagnoses. Another important point is that the presence of other clinically important illnesses does not exclude a diagnosis of FM [21]. In 2018, considering important but less visible factors that have a profound influence on under- or over-diagnosis of FM provided a new gate to a holistic and real understanding of FM diagnosis, beyond existing arbitrary and constructional scores [22]. Int. J. Mol. Sci. 2020, 21, 7877 4 of 27 Table 1. ACR2010 and modified criteria for the diagnosis of fibromyalgia. Widespread pain index (WPI) Areas specification Number of areas in which the patient has had 0–19 points pain over the past week shoulder girdle, hip (buttock, trochanter), jaw, upper back, lower back, upper arm, upper leg, chest, neck, abdomen, lower arm, Areas to be considered and lower leg (all these areas should be considered bilaterally) Symptom Severity Scale (SSS) score Symptom Level of severity Symptom level Score For each of these 3 symptoms, indicate the level of severity over the past week Considering somatic symptoms in using the following scale: Fatigue general, indicate whether the patient has 0 = no problem Waking unrefreshed the following: 1 = slight or mild problems, generally Cognitive symptoms (e.g., working memory 0 = no symptoms Final score between 0 and 12 mild or intermittent capacity, recognition memory, verbal knowledge, 1 = few symptoms 2 = moderate; considerable problems, anxiety, and depression) 2 = a moderate number of symptoms often present and/or at a moderate level 3 = a great deal of symptoms 3 = severe; pervasive, continuous, life-disturbing problems Criteria Specification Conditions A patient satisfies diagnostic criteria for (a)WPI 7/19 and SS scale score 5 or WPI 3–6 and SS scale score 9 fibromyalgia if the following 3 conditions (b) symptoms have been present as a similar level for at least 3 months are met (c) the patient does not have a disorder that would otherwise explain the pain Modified criteria Specification Conditions Final Score (a)WPI (as above) A patient satisfies diagnostic criteria for (b) SS scale score (as above, but without The number of pain sites (WPI), the SS scale score, and the presence of associated fibromyalgia if the following 3 conditions extent of somatic symptoms) symptoms are summed to give a final score between 0 and 31 are met (c) presence of abdominal pain, depression, headaches (yes = 1, no = 0) Int. J. Mol. Sci. 2020, 21, 7877 5 of 27 In 2019, in cooperation with the WHO, an IASP Working Group has developed a classification system included in the International Classification of Diseases (ICD-11) where FM has been classified as chronic primary pain, to distinguish it from pain which is secondary to an underlying disease [23]. More recently, a study of about 500 patients under diagnosis of FM, revealed that 24.3% satisfied the FM criteria, while 20.9% received a clinician International Classification of Diseases (ICD) diagnosis of FM, with a 79.2% agreement between clinicians and criteria. The conclusions of this study pointed out a disagreement between ICD clinical diagnosis and criteria-based diagnosis of FM, calling into question meaning of a FM diagnosis, the validity of physician diagnosis and clinician bias [24]. FM is a disorder that cannot be based on diagnosis of exclusion, rather needing positive diagnosis [6], through a multidimensional FM diagnostic approach making diagnosis encompassing psychosocial stressors, subjective belief, psychological factors and somatic complaints [25]. The advent of the PSD scale identified a number of problems in FM research [16]. Recently, immunophenotyping analysis performed on blood samples of FM patients revealed a role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM [26]. Moreover, a rapid biomarker-based method for diagnosing FM has been developed by using vibrational spectroscopy to di↵erentiate patients with FM from those with other pain-related diseases. Unique IR and Raman spectral signatures were correlated with FM pain severity measured with FM impact questionnaire revised version (FIQR) [27]. Overall, these findings provide reliable diagnostic tests for di↵erentiating FM from other disorders, for establishing serologic biomarkers of FM-associated pain and were useful for the contribution of the legitimacy of FM as a truly painful disease. In summarizing aspects of FM learned through applications of criteria to patients and trials, Wolfe [28] identified 7 main concepts: 1) there is no way of objectively testing FM which also has no binding definition; 2) prevalence and acceptance of FM depend on factors largely external to the patient; 3) FM is a continuum and not a categorical disorder; 4) every feeling, symptom, physical finding, neuroscience measure, cost and outcome tells one very little about the disorder and its mechanisms when fibromyalgia to “normal subjects” is compared; 5) the range and content of symptoms might indicate that FM may not truly be a syndrome; 6) “pain and distress” type of FM subject identified in the general population [29] might be considered as part of the FM definition and; 7) caution is needed when accepting the current reductive neurobiological causal explanations as sufficient, since FM is a socially constructed and arbitrarily defined and diagnosed dimensional disorder. 3. Therapy 3.1. Pharmacotherapy of FM Clinical trials have failed to conclusively provide overall benefits of specific therapies to treat FM; therefore, current pharmacological treatments for patients su↵ering from FM are mainly directed to palliate some symptoms, with relevant clinical benefits experienced only by a minority of individuals from any one intervention. In those treated with pharmacotherapy, a 50%reduction in pain intensity is generally achieved only by 10% to 25% [30] However, some treatments seem to significantly improve the quality of life of certain FM patients [31]. Only a few drugs have been approved for use in the treatment of FM by the US FDA, whereas no drug has been approved for this indication by the European Medicines Agency. Thus patients with FM frequently need to be treated on an o↵-label basis [32]. Currently, only 25% to 40% pain reduction is granted by drugs and meaningful relief occurs in only 40% to 60%, in part due to dose-limiting adverse e↵ects and incomplete drug efficacy [33]. These limitations in clinical practice have led some to hypothesize that a combination of di↵erent analgesic drugs acting through di↵erent mechanisms may provide superior outcomes compared to monotherapy [34]. Moreover, drugs should be started at low doses and cautiously increased because some patients, either do not tolerate or benefit from drug therapy. Because sleep disturbance, pain and psychological distress are the most amenable to drug therapy, drugs should be chosen to manage the individual’s predominant symptoms [35]. Currently, several drugs are frequently used alone Int. J. Mol. Sci. 2020, 21, 7877 6 of 27 or in combination to manage FM symptoms; however, the US FDA indicated for FM only three: two selective serotonin and norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, and an anticonvulsant, pregabalin [36]. In the next sections, the use of selected drugs aimed to alleviate FM will be described. 3.1.1. Cannabinoids in FM Therapy The cannabinoid system is ubiquitous in the animal kingdom and plays multiple functions with stabilizing e↵ects for the organism, including modulation of pain and stress, and the management of FM may have therapeutic potential by manipulating this system. The cannabinoid system contributes in maintaining equilibrium and stabilizing e↵ects on FM [37]. Moreover, the endocannabinoid neuromodulatory system is involved in multiple physiological functions, such as inflammation and immune recognition, endocrine function, cognition and memory, nausea, antinociception and vomiting, [38]. Deficiency in the endocannabinoid system has been correlated to FM [39], but without clear clinical evidence in support of this assumption [40]. The endocannabinoid system consists of two cannabinoid receptors, the CB1 and CB2 receptors [41]. In acute and chronic pain models, analgesic e↵ects are associated to CB1 agonists that act at many sites along pain transmission pathways, including activation of spinal, supraspinal and peripheral CB1 receptors, each independently decreasing nociception [42]. Delta 9-tetrahydrocannabinol (D9-THC or Dronabinol, 1) is the main active constituent of Cannabis sativa var indica, with psychoactive and pain-relieving properties. The non-selective binding to G-protein-coupled CB receptors is responsible for the pharmacological e↵ects induced by D9-THC. Cannabidiol (CBD, 2), a non-psychotropic constituent of cannabis, is a high potency antagonist of CB receptor agonists and an inverse agonist at the CB2 receptor [43]. CBD displays CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor [44]. This CB2 receptor inverse agonist ability of CBD may contribute to its documented anti-inflammatory properties [44]. The main endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA, 3) and 2-arachidonoylglycerol (2-AG, 4), AG), the activity of which is modulated by the hydrolyzing fatty acid palmitoylethanolamide (PEA, 5) and the endocannabinoid precursor arachidonic acid (AA, 6) [45]. AEA and 2-AG are functionally related to D9-THC [46]. It was found that stress induces a rapid anandamide release in several CNS regions resulting in stress-induced analgesia via CB1 receptors [47]. FM patients had significantly higher anandamide plasma levels [39,46]; however, it has been suggested that the origin of FM and chronic pain depend on a deficiency in the endocannabinoid signaling [45]. Monotherapies of FM based on D9-THC are based on the assumption that this compound acts as an analgesic drug; however, although a sub-population of FM patients reported significant benefits from the use of D9-THC, this statement cannot be made [48]. When the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users, a significant improvement of symptoms of FM in patients using cannabis was observed, although there was a variability of patterns [49]. The synthetic cannabinoid nabilone (7) showed of a superiority over placebo to reduce FM symptoms, with significant reductions in Visual Analog Scale (VAS) for pain, FM Impact Questionnaire (FIQ), and anxiety [42], indicating the efficacy of treating people with FM with nabilone. Nabilone was also e↵ective in improving sleep [50]; however, participants taking nabilone experienced more adverse events (such as dizziness/drowsiness, dry mouth and vertigo) than did participants taking placebo or amitriptyline (see below). The self-medication practice of herbal cannabis was associated with negative psychosocial parameters. Therefore, caution should be exercised in recommending the use of cannabinoids pending clarification of general health and psychosocial problems [51,52]. Figure 3 illustrates the chemical formulas of some cannabinoids and endocannabinoids. Int. J. Mol. Sci. 2020, 21, 7877 7 of 27 Figure 3. Structure formulae of some cannabinoids and related compounds. Numbers correspond to compound names cited in the text. 3.1.2. Opioids in FM Therapy One of the major natural sources of opioids is the medicinal plant Papaver somniferum. Although clinical evidence demonstrating the efficacy or e↵ectiveness of opioids analgesics is scanty, these molecules are widely used for the treatment of FM [53]. However, the long-term use of opioids in FM has been discouraged by several medical guidelines [54]. The use of opioids is documented in studies demonstrating increased endogenous opioid levels in the cerebrospinal fluid of patients with FM vs. controls [55]. These results prompted the interesting hypothesis that a more activated opioid system can be detected in individuals with FM, reflecting reduced receptor availability and increased release of endogenous opioids [54]. There is evidence from both single center, prospective, longitudinal and multicenter and observational clinical studies of negative e↵ects of the use of opioids in FM on patient outcomes compared with other therapies [56,57]. Moreover, opioid user groups showed less improvement in the SFM-36 subscale scores of general health perception and in the FIQ subscale scores of job ability, fatigue and physical impairment [58]. Furthermore, altered endogenous opioid analgesic activity in FM has been demonstrated and suggested as a possible reason for why exogenous opiates appear to have reduced efficacy [59]. Despite these facts, opioids have been prescribed for 10% to 60% of patients with FM as reported in large database sets [54]. When considered, the preference of patients appears towards opioids. In a survey, 75% of patients considered hydrocodone (8) plus acetaminophen to be helpful, and 67% considered oxycodone (9) plus acetaminophen to be helpful [60]. FM has been associated with preoperative opioid use, including hydrocodone [61], whereas there is limited information from randomized controlled trials on the benefits or harms of oxycodone when used to treat pain in FM [62]. A pilot study showed that naltrexone (10) reduced self-reported symptoms of FM (primarily daily pain and fatigue) [63] and further studies showed that low-dose naltrexone had a specific and clinically beneficial impact on FM. This opioid, which is widely available and inexpensive, Int. J. Mol. Sci. 2020, 21, 7877 8 of 27 was found to be safe and well-tolerated. Blocking peripheral opioid receptors with naloxone (11) was observed to prevent acute and chronic training-induced analgesia in a rat model of FM [64]; however, there were no significant e↵ects of naloxone nor nocebo on pressure pain threshold, deep tissue pain, temporal summation or conditioned pain modulation in chronic fatigue syndrome/FM patients [65]. A synthetic opioid receptor agonist that shows serotonin-norepinephrine reuptake inhibitor properties is tramadol (12); this compound is often prescribed for painful conditions [66]. Tramadol has been studied in humans who su↵er from FM [56], suggesting that tramadol may be e↵ective in treating FM [67]. The use of tramadol provides change in pain assessed by visual analogue scale and FM impact questionnaire; however, the reported side e↵ects include dizziness, headache, constipation, addiction, withdrawal, nausea, serotonin syndrome, somnolence, pruritus seizures, drug–drug interactions with antimigraine and antidepressants medications [66]. Therefore, it is recommended that tramadol application should be considered in refractory and more treatment-resistant cases of FM. Another weak opioid is codeine (13). In a comparative study, there was a significantly higher proportion of patients in the codeine-acetaminophen group reporting somnolence or constipation and a larger proportion of patients in the tramadol-acetaminophen group reporting headache. The overall results suggested that tramadol-acetaminophen tablets (37.5 mg/325 mg) were as e↵ective as codeine-acetaminophen capsules (30 mg/300 mg) in the treatment of chronic pain [68]. Fentanyl (14) works primarily by activating µ-opioid receptors and was found to be around 100 times stronger than morphine (15), although its e↵ects are more localized. Fentanyl injections reduced second pain from repeated heat taps in FM patients. Similar to reports of e↵ects of morphine on first and second pain, fentanyl had larger inhibitory e↵ects on slow temporal summation of second pain than on first pain from a nociceptor stimulation [69]. Since fentanyl can inhibit windup of second pain in FM patients, it can prevent the occurrence of intense summated second pain and thereby reduce its intensity by a greater extent than first or second pains evoked by single stimuli. Among the 70,237 drug-related deaths estimated in 2017 in the US, the sharpest increase occurred among those related to fentanyl analogs with almost 29,000 overdose deaths which represents more than 45% increase from 2016 to 2017 [70]. Because the numbers of overdoses and deaths due to fentanyl will continue to increase in the coming years, studies are needed to elucidate the physiological mechanisms underlying fentanyl overdose in order to develop e↵ective treatments aimed to reduce the risk of death [71]. Glial cell activation is one of the several other possible pathophysiologic mechanisms underlying the development of FM by contributing to central nervous system sensitization to nociceptive stimuli [72]. Pentoxifylline (16), a xanthine derivative used as a drug to treat muscle pain in people with peripheral artery disease, is a nonspecific cytokine inhibitor that has been shown to attenuate glial cell activation and to inhibit the synthesis of TNF↵, IL-1 , and IL-6 [73]. In theory, attenuating glial cell activation via the administration of pentoxifylline to individuals su↵ering from FM might be efficient in ameliorating their symptoms without being a globalist therapeutic approach targeting all possible pathophysiologic mechanisms of development of the syndrome [74]. With regards FM pathophysiology, serum brain-derived neurotrophic factors (BDNF) were found at higher levels in FM patients while BDNF methylation in exon 9 accounted for the regulation of protein expression. These data suggest that altered BDNF levels might represent a key mechanism explaining FM pathophysiology [75]. Opioid users were also observed to experience a decreased pain and symptom severity when ca↵eine (17) was consumed, but this was not observed in opioid nonusers, indicating ca↵eine may act as an opioid adjuvant in FM-like chronic pain patients. Therefore the consumption of ca↵eine along with the use of opioid analgesics could represent an alternative therapy with respect to opioids or ca↵eine alone [76]. Figure 4 shows the chemical formulae of some opioids used in FM therapy. Int. J. Mol. Sci. 2020, 21, 7877 9 of 27 Figure 4. Structure formulae of some opioids and related compounds. Numbers correspond to molecules cited in the text. 3.1.3. Gabapentinoids in FM Therapy Gabapentinoid drugs are US Food and Drug Administration (FDA) (but not in Europe) anticonvulsants approved for treatment of pain syndromes, including FM. However, FDA approved pregabalin (18) but not gabapentin (19) for FM treatment; nevertheless, gabapentin is often prescribed o↵-label for FM, presumably because it is substantially less expensive [77]. Pregabalin is a gamma-aminobutyric acid (GABA) analog and is a ligand for the ↵2 subunit of the calcium channel being able of reducing the ability of docked vesicles to fuse and release neurotransmitters [78]. Pregabalin shows e↵ects on cortical neural networks, particularly when basal neurons are under hyperexcitability. The pain measures and pregabalin impact on the cortical excitability was observed only in FM patients [79]. Pregabalin was also found to increase norepinephrine levels in reserpine-induced myalgia rats [80]. Because of its tolerability when used in combination with antidepressants, pregabalin use showed a very good benefit to risk ratio [81]. The starting approved dosage for pregabalin is at 150 mg daily [82]; however, the drug shows a higher e↵ectiveness when used at a dose of 300 or 600 mg/day. Lower pregabalin doses than those of clinical trials are used in clinical practice because higher doses are more likely to be intolerable [83]. A recent systematic review shows that a minority of people with moderate to severe pain due to FM treated with a daily dose of 300 to 600 mg of pregabalin had a reduction of pain intensity over a follow-up period of 12 to 26 weeks, with tolerable adverse e↵ects [84]. Thus, pregabalin is one of cardinal drugs used in the treatment of FM, and its clinical utility has been comprehensively demonstrated [85,86]. Nevertheless, there is still insufficient evidence to support or refute that gabapentin may reduce pain in FM [87]. Figure 5 depicts the chemical formulae of some gabapentinoids. Int. J. Mol. Sci. 2020, 21, 7877 10 of 27 Figure 5. Structure formulae of some gabapentinoids. Numbers correspond to molecules cited in the text. 3.1.4. Serotonin–Norepinephrine Reuptake Inhibitors in FM Therapy There is a wide use of serotonin and noradrenaline reuptake inhibitors (SNRIs). There is no unbiased evidence that serotonin selective reuptake inhibitors (SSRIs) are superior to placebo in treating depression in people with FM and for treating the key symptoms of FM, namely sleep problems, fatigue and pain. However, it should be considered that young adults aged 18 to 24, with major depressive disorder, showed an increased suicidal tendency when treated with SSRIs [88]. A recent Cochrane review evaluated the use of SNRIs including eighteen studies with a total of 7,903 adults diagnosed with FM, by using desvenlafaxine (20) and venlafaxine (21) in addition to duloxetine (22) and milnacipran (23), by considering various outcomes for SNRIs including health related quality of life, fatigue, sleep problems, pain and patient general impression, as well as safety and tolerability [89]. Fifty two percent of those receiving duloxetine and milnacipran had a clinically relevant benefit over placebo compared to 29% of those on placebo, with much or very much improvements in the intervention. On the other hand, reduction of pain intensity was not significantly di↵erent from placebo when desvenlafaxine was used. However, pain relief and reduction of fatigue was not clinically relevant for duloxetine and milnacipran in 50% or greater and did not improve the quality of life [90]. Same negative outcomes were found for reducing problems in sleep and the potential general benefits of duloxetine and milnacipran were outweighed by their potential harms. The efficacy of venlafaxine in the treatment of FM was studied to a lesser extent. The lack of consistency in venlafaxine dosing, placebo control and blinding make difficult to understand whether the molecule is e↵ective in treating FM. Nevertheless, tolerability and the lower cost of venlafaxine increases its potential use for the treatment of FM, by rendering the molecule a more a↵ordable option compared to the other, more expensive SNRIs [91]. Mirtazapine (24) promotes the release of noradrenaline and serotonin by blocking ↵2 -adrenergic autoreceptors and ↵2 -adrenergic heteroreceptors, respectively. Mirtazapine, by acting through 5-HT1A receptors and by blocking postsynaptic 5-HT2A , 5-HT2C , and 5-HT3 receptors is able to enhance serotonin neurotransmission [92]. For these properties, mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant [93]. Mirtazapine appears to be a promising therapy to improve sleep, pain, and quality of life in patients with FM [94]. In Japanese patients with FM, mirtazapine caused a significantly greater reduction in the mean numerical rating scale pain score and remained significantly greater from week 6 onward, compared with placebo. However, Adverse mirtazapine caused adverse events including weight gain, somnolence and increased appetite when compared to placebo [92]. Among antidepressants, the tricyclic antidepressant (TCAs) amitriptyline (25) was studied more than other antidepressants. It is frequently used to assess comparative efficacy [95] and for many years amitriptyline has been a first-line treatment for FM. Although there is no supportive unbiased evidence for a beneficial e↵ect, the drug was successful for the treatment in many patients with FM. However, amitriptyline achieve satisfactory pain relief only by a minority of FM patients and is unlikely that any large randomized trials of amitriptyline will be conducted in FM to establish efficacy Int. J. Mol. Sci. 2020, 21, 7877 11 of 27 statistically, or measure the size of the e↵ect [96]. Figure 6 depicts the chemical formulae of some SNRIs and TCA. Figure 6. Chemical structure of some serotonin and noradrenaline reuptake inhibitors and a tricyclic antidepressant. Numbers correspond to molecules cited in the text. 3.2. Alternative Therapies for FM A survey of the European guidelines shows that most of the pharmacological therapies are relatively modest providing only weak recommendations for FM [97]. A multidimensional approach is therefore required for the management of FM, including pharmacological therapies along with behavioral therapy, exercise, patient education and pain management. A multidisciplinary approach combines pharmacotherapy with physical or cognitive interventions and natural remedies. Very often, patients seek help in alternative therapies due to the limited efficacy of the therapeutic options. The following sections discuss some of the most used alternative therapies to treat FM. 3.2.1. Acupunture Acupuncture shows low to moderate-level in improving pain and sti↵ness in people with FM. In some cases, acupuncture does not di↵er from sham acupuncture in improving sleep or global well-being or reducing pain or fatigue. The mechanisms of acupuncture action in FM treatment appears to be correlated to changes in serum serotonin levels [98]. Electro-acupuncture (EA) was more e↵ective than manual acupuncture (MA) for improving sleep, global well-being and fatigue and in the reduction of pain and sti↵ness. Although e↵ective, the e↵ect of acupuncture is not maintained at six months follow-up [99]. Moreover, there is a lack of evidence that real acupuncture significantly di↵ers from sham acupuncture with respect to improving the quality of life, both in the short and long term. However, acupuncture therapy is a safe treatment for patients with FM [100,101]. 3.2.2. Electric Stimulation As we discussed, FM, aside pain, is characterized by anxiety, depression and sleep disturbances, and by a complex cognitive dysfunctioning status known as “fibrofog” which is characterized by disturbance in working memory, attention and executive functions globally often referred by the patients as a sense of slowing down, clumsiness and confusion that have a profound impact on the ability to perform and e↵ectively plan daily activities [102,103]. Besides stimulation with acupuncture, the e↵ective modulation of brain areas has been obtained through non-invasive brain stimulation by Int. J. Mol. Sci. 2020, 21, 7877 12 of 27 magnetic or electric currents applied to the scalp like transcranial magnetic and electrical stimulation. In many cases, to relieve pain and improve general FM-related function, the use of anodal transcranial direct current stimulation over the primary motor cortex was found to be significantly more e↵ective than sham transcranial direct current stimulation [104]. If we consider that pharmacological and non-pharmacological treatments are often ine↵ective or transitory in their e↵ect on FM, therapeutic electrical stimulation appears to have a potential role [105]. Cognitive functions such as memory have been enhanced in FM patients by anodal transcranial direct current stimulation over the dorsolateral prefrontal cortex and has clinical relevance for top-down treatment approaches in FM [106]. In FM patients, modulation of hemodynamic responses by transcutaneous electrical nerve stimulation during delivery of nociceptive stimulation was also investigated and shown to be an e↵ective factor in FM treatment, although the underlying mechanism for these findings still needs to be clarified [107]. It has been recently demonstrated that both transcutaneous electric nerve stimulation and acupuncture applications seem to be beneficial in FM patients [108]. In a recent Positron Emission Tomography H2 15 O activation study it was shown that occipital nerve field stimulation acts through activation of the descending pain inhibitory pathway and the lateral pain pathway in FM, while electroencephalogram shows activation of those cortical areas that could be responsible for descending inhibition system recruitment [109]. Microcirculation is of great concern in patients with FM. Recently low-energy pulsed electromagnetic field therapy was found to increase a promising therapy to increase microcirlulation [110]; however, neither pain and sti↵ness were reduced nor functioning was improved by this therapy in women with FM [111]. The European Academy of Neurology, based on the method of GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) judged anodal transcranial direct currents stimulation of motor cortex as still inconclusive for treatment of FM [112]. Therefore, further studies are needed to determine optimal treatment protocols and to elucidate the mechanisms involved [113]. 3.2.3. Vibroacoustic and Rhythmic Sensory Stimulation Stimulation with sensory events such as pulsed or continuous auditory, vibrotactile and visual flickering stimuli are referred as rhythmic sensory stimulation [114]. Clinical studies have reported the application of vibroacoustic stimulation in the treatment of FM. In a clinal study, one group of patients with FM listened to a sequence of Bach’s compositions, another was subjected to vibratory stimuli on a combination of acupuncture points on the skin and a third group received no stimulation. The results showed that a greater e↵ect on FM symptoms was achieved by the combined use of music and vibration [115]. However, in another study, neither music nor musically fluctuating vibration had a significant e↵ect on tender point pain in FM patients when compared to placebo treatment [116]. Because thalamocortical dysrhythmia is implicated in FM and that low-frequency sound stimulation can play a regulatory function by driving neural rhythmic oscillatory activity, volunteers with FM were subjected to 23 min of low-frequency sound stimulation at 40 Hz, delivered using transducers in a supine position. Although no adverse e↵ects in patients receiving the treatment, no statistically and clinically relevant improvement were observed [117]. On the other hand, gamma-frequency rhythmic vibroacoustic stimulation was found to decrease FM symptoms (depression, sleep quality and pain interference) and ease associated comorbidities (depression and sleep disturbances), opening new avenues for further investigation of the e↵ects of rhythmic sensory stimulation on chronic pain conditions [118]. 3.2.4. Thermal Therapies Thermal therapies have been used to treat FM. Two main therapies are currently used: body warming and cryotherapy. Int. J. Mol. Sci. 2020, 21, 7877 13 of 27 Because FM is strongly linked to rheumatic aches, the application of heat by spa therapy (balneotherapy) appears as a natural choice for the treatment of FM [119]. Spa therapy is a popular treatment for FM in many European countries, as well as in Japan and Israel. A randomized prospective study of a 10-day treatment was done on 48 FM patients improving their quality of life [120] and showed that treatment of FM at the Dead Sea was both e↵ective and safe [121]. FM patients who were poorly responding to pharmacological therapies were subjected to mud-bath treatment. A cycle of mud bath applications showed beneficial e↵ects on FM patients whose evaluation parameters remained stable after 16 weeks in comparison to baseline [122]. In patients su↵ering from FM, mud bathing was also found to prevent muscle atrophy and inflammation and improve nutritional condition [123]. Nevertheless, despite positive results, the methodological limitations of available clinical studies, such as the lack of placebo double-blinded trials, preclude definitive conclusions on the e↵ect of body-warming therapies to treat FM [119,124]. A remedy widely used in sports related trauma is the application of cold as a therapeutic agent for pain relief. Cryotherapy refers to the use of low temperatures to decrease the inflammatory reaction, including oedema [125]. Cryotherapy induces several organism physiological reactions like increasing anti-inflammatory cytokines, beta-endorphins, ACTH, white blood cells, catecholamines and cortisol, immunostimulation due to noradrenalin response to cold, the increase in the level of plasma total antioxidant status and the reduction of pain through the alteration of nerve conduction [126]. When compared to control FM subjects, cryotherapy-treated FM patients reported a more pronounced improvement of the quality of life [127]. Whole body cryotherapy was also found to be a useful adjuvant therapy for FM [126]. 3.2.5. Hyperbaric Treatment Hyperbaric oxygen therapy (HBOT) has shown beneficial e↵ects for the prevention and treatment of pain [128], including migraine, cluster headache [129] and FM [130]. HBOT is supposed to induce neuroplasticity that leads to repair of chronically impaired brain functions. HBOT was also found to it improve the quality of life in post-stroke patients and mild traumatic brain injury patients [131]. Therefore, the increased oxygen concentration caused by HBOT is supposed to change the brain metabolism and glial function with a potential e↵ect on reducing the FM-associated brain abnormal activity [132]. HBOT was found to a↵ect the mitochondrial mechanisms resulting in functional brain changes, stimulate nitric oxide production thus alleviating hyperalgesia and promoting the NO-dependent release of endogenous opioids which appear to be involved in the antinociception prompted by HBOT [133]. In a clinical study, a significant di↵erence between the HBOT and control groups was found in the reduction in tender points and VAS scores after the first and fifteenth therapy sessions [130]. These results indicate that HBOT may play an important role in managing FM. 3.2.6. Laser Therapy and Phototherapy The use of di↵erent light wavelengths has been found to be an alternative therapy for FM. It is known that low-level laser therapy is a therapeutic factor, being able not only to target one event in the painful reception, but rather the extend its e↵ectiveness on the whole hierarchy of mechanisms of its origin and regulation [134]. Laser photobiomodulation therapy has been reported to be e↵ective in the treatment of a variety of myofascial musculoskeletal disorders, including FM [135]. The combination of laser therapy and the administration of the drug amitriptyline was found to be e↵ective on clinical symptoms and quality of life in FM; furthermore, gallium-arsenide laser therapy was found to be a safe and e↵ective treatment which can be used as a monotherapy or as a supplementary treatment to other therapeutic procedures in FM [136]. Evidence supported also the use of laser therapy in women su↵ering FM to improve pain and upper body range of motion, ultimately reducing the impact of FM [137,138]. Finally, a combination of phototherapy and exercise training was evaluated in patients with FM in a randomized controlled trial for chronic pain to o↵er valuable clinical evidence for objective assessment of the potential benefits and risks of procedures [139]. Int. J. Mol. Sci. 2020, 21, 7877 14 of 27 3.2.7. Exercise and Massage Exercise therapy seems to be an e↵ective component of treatment, yielding improvement in pain and other symptoms, as well as decreasing the burden of FM on the quality of life [140]. Exercise is generally acceptable by individuals with FM and was found to improve the ability to do daily activities and the quality of life and to decrease tiredness and pain [141]. However, it is important to know the e↵ects and specificities of di↵erent types of exercise. For instance, two or more types of exercise may combine strengthening, aerobic or stretching exercise; however, there is no substantial evidence that mixed exercise may improve sti↵ness [142]. Quality of life may be improved by muscle stretching exercise, especially with regard to physical functioning and pain, whereas depression is reduced by resistance training. A trial including a control group and two intervention groups, both of which receiving exercise programs created specifically for patients with FM, showed that both modalities were e↵ective in an exercise therapy program for FM [143]. A progressive muscle strengthening activity was also found to be a safe and e↵ective mode of exercise for FM patients [144]. Furthermore, strength and flexibility exercises in aerobic exercise rehabilitation for FM patients led to improvements in patients’ shoulder/hip range of motion and handgrip strength [145]. Among women with FM, the association between physical activity and daily function is mediated by the intensity of musculoskeletal pain, rather than depressive symptoms or body mass [146], with a link between clinical and experimental pain relief after the performance of isometric contractions [147]. A randomized controlled trial evaluated the e↵ects of yoga intervention on FM symptoms. Women performing yoga showed a significant improvement on standardized measures of FM symptoms and functioning, including fatigue, mood and pain, and in pain acceptance and other coping strategies [148]. Moreover, the combination with massage therapy program during three months influenced perceived stress index, cortisol concentrations, intensity of pain and quality of life of patients with FM [149]. In terms of societal costs and health care costs, quality of life and physical fitness in females with FM was improved by aquatic training and subsequent detraining [150,151]. Aquatic physical training was e↵ective in promoting increased oxygen uptake at peak cardiopulmonary exercise test in women with FM [152]. A systematic evaluation of the harms and benefits of aquatic exercise training in adults with FM showed that it may be beneficial for improving wellness, symptoms, and fitness in adults with FM [153,154]. A safe and clinically efficacious treatment of pain and other FM symptoms was also achieved by the combination of osteopathic manipulative medicine and pharmacologic treatment with gabapentin [155]. Dancing is a type of aerobic exercise that may be used in FM alternative therapy. Belly dancing was found to be e↵ective in improving functional capacity, pain, quality of life and improving body image of women with FM [156]. More recently, three months treatment of patients with FM with Zumba dancing was found to be e↵ective in improving pain and physical functioning [157]. Finally, Tai chi mind-body treatment was found to improve FM symptoms as much as aerobic exercise and longer duration of Tai chi showed greater improvement. According to a recent report, mind-body approaches may take part of the multidisciplinary management of FM and be considered an alternative therapeutic option [158]. 3.2.8. Probiotics and FM Therapy A tractable strategy for developing novel therapeutics for complex central nervous system disorders could rely on the so called microbiota-gut-brain axis management, because intestinal homeostasis may directly a↵ect brain functioning [159,160]. The pain intensity of patients with FM has been reported to be correlated with the degree of small intestinal bacterial overgrowth, which is often associated with an increased intestinal permeability whose values were significantly increased in the FM patients [161]. Preclinical trials indicate that the microbiota and its metabolome are likely involved in modulating brain processes and behaviors [162]. Therefore, FM patients should show better performance after the treatment with probiotics. In a double-blind, placebo-controlled, randomized design probiotic Int. J. Mol. Sci. 2020, 21, 7877 15 of 27 improved impulsive choice and decision-making in FM patients, but no other e↵ects were observed on cognition, quality of life, self-reported pain, FM impact, depressive or anxiety symptoms [163]. 3.2.9. Use of Plant Extracts and Natural Products for FM Treatment About 40% of drugs used to treat FM originate from natural products [164]; however, there are a few studies that prove the safe and e↵ective use of various plant extracts in FM therapy. Several plant extracts are currently used for their antinociceptive properties and potential to treat FM [165]. Papaver somniferum is probably the most ancient plant used for its antinociceptive properties [166], with chemical components able to interact with opioid receptors; among these morphine (15) which is not only the oldest, but is still the most e↵ective drug for the management of severe pain in clinical practice [167]. The use of opioids for FM treatment has been discussed above. Another important plant is Cannabis sativa. The major active constituent of Cannabis, D9-THC (1), has been shown to possess antinociceptive properties when assessed in several experimental models [168] (see also the discussion above on cannabinoids). Although there is still scarce evidence to support its role in the treatment of FM, a large consensus indicates that medical cannabis could be an e↵ective alternative for the treatment of FM symptoms [169]. The illicit use of herbal cannabis for FM treatment has been correlated to the inefficacy of current available medications, but is also linked to popular advocacy or familiarity with marijuana from recreational use. Therefore, physicians are requested to examine the global psychosocial well-being, and not focus only on the single outcome measure of pain [52,170]. Although medical cannabis treatment has a significant favorable e↵ect on patients with FM, 30% of patients experience adverse e↵ects [171] and 8% report dependence on cannabis [172]. VAS scores measured in 28 FM patients after 2 hours of cannabis use showed enhancement of relaxation and feeling of well-being, a reduction of pain and sti↵ness which were accompanied by an increase in somnolence. The mental health component summary score of the Short Form 36 Health Survey was higher in cannabis users than in non-users [49]. Among terpenoids, administration of trans- -caryophyllene (BCP, 26), a bicyclic sesquiterpene compound existing in the essential oil of many plants like Copaifera langsdforffii, Cananga odorata, Humulus lupulus, Piper nigrum and Syzygium aromaticum, which provide a high percentage of BCP along with interesting essential oil yields [173], significantly minimized the pain in both acute and chronic pain models [174]. BCP selectively binds to the cannabinoid 2 (CB2 ) receptor and is a functional CB2 agonist. Upon binding to the CB2 receptor, BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes [175]. BCP, a safe compound with toxicity at doses higher than 2000 mg/kg body weight [176], was found to reduce the primary and secondary hyperalgesia produced by a chronic muscle pain model (which is considered to be an animal model for FM) [177]. Significant and dose-dependent antinociceptive response was produced by BCP without the presence of gastric damage [178]. Antiallodynic actions of BCP are exerted only through activation of local peripheral CB2 [179]. In neuropathic pain models, BCP reduced spinal neuroinflammation and the oral administration was more e↵ective than the subcutaneously injected synthetic CB2 agonist JWH-133 [180]. Recently, BCP was found to exert an analgesic e↵ect in an FM animal model through activation of the descending inhibitory pain pathway [181]. Thus, BCP may be highly e↵ective in the treatment of long-lasting, debilitating pain states, suggesting the interesting application of BCP in FM therapy. The analgesic properties of myrrh (Commiphora myrrha) have been known since ancient times and depend on the presence of bioactive sesquiterpenes with furanodiene skeletons which are able to interact with the opioid receptors [182,183]. C. myrrha extracts exerted a stronger suppression on carrageenan-induced mice paw edema with significant analgesic e↵ects [184] and were e↵ective against chronic inflammatory joint disease such as osteoarthritis [185]. In a preclinical trial, pain alleviation was obtained with C. myrrha extracts for many pathologies [186], indicating that extracts from this plant may have the potential to treat FM. Int. J. Mol. Sci. 2020, 21, 7877 16 of 27 Preclinical studies indicate a potential use of Hypericum perforatum (Hypericaceae), popularly known as St. John’s wort, in medical pain management [187] due to its phenolic compounds. Many phenolic compounds (e.g., flavonoids) from medicinal plants are promising candidates for new natural analgesic drugs [188]. Quercetin (27) showed analgesic activity and could reduce neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons of db/db mice [189], while rutin (28) could inhibit the writhing response of mice induced by potassium antimony tartrate and showed to be a promising pharmacological approach to treat pain [190]. The analgesia potency of hyperin (29) was approximately 20-fold of morphine, while luteolin (30) presented e↵ective analgesic activities for both acute and chronic pain management. Some glycosides of kaempferol (e.g., kaempferol 3-O-sophoroside, 31) possess significant analgesic activity in the tail clip, tail flick, tail immersion, and acetic acid-induced writhing models, whereas baicalin (32) shows analgesic e↵ects in several kinds of pain [191]. Fisetin (33), a plant flavonoid polyphenol, has been reported to possess potent antioxidant, antinociceptive and neuroprotective activities. In rats, fisetin acts via modulation of decreased levels of biogenic amines and elevatesoxido-nitrosative stress and ROS to ameliorate allodynia, hyperalgesia, and depression in experimental reserpine-induced FM [192]. In a double-blind parallel-group clinical trial, outpatients with FM were randomized to receive either 15 mg of Crocus sativus (sa↵ron) extract or 30 mg duloxetine (22). No significant di↵erence was detected for any of the scales neither in terms of score changes from baseline to endpoint between the two treatment arms, indicating that sa↵ron and duloxetine had comparable efficacy in treatment of FM symptoms [193]. It is still unclear the efficacy of natural products extracted from plants in treating FM. However, some clinical data show promising results and more studies with adequate methodological quality are necessary in order to investigate the efficacy and safety of natural products as a support in FM therapy. Figure 7 depicts the chemical formulae of some antinociceptive natural products. Figure 7. Chemical structure of some natural compounds with antinociceptive activity. Int. J. Mol. Sci. 2020, 21, 7877 17 of 27 4. Conclusions Diagnosis of FM is based on clinical feature and criteria that still lack either a gold standard or at least supportive laboratory findings. FM diagnostic criteria may include heterogeneous patients also in clinical trials and this may impair evaluation of clinically meaningful treatment e↵ect. The review of the literature suggests that a multidisciplinary therapeutic approach, based on the combination of pharmacologic and alternative therapy (including thermal, light, electrostimulatory and body exercise treatments) could improve the quality of life and reduce pain and other symptoms related to FM. However, sometimes the ability of patients to participate to alternative therapies is impeded by the level of pain fatigue, poor sleep, and cognitive dysfunction. These patients may need to be managed with medications before initiating nonpharmacologic therapies. Although the use of some natural phytochemicals like BCP and phenolic compounds might replace other natural products such as D9-THC, because of reduced side e↵ects and higher tolerability, FM self medication practice may be ine↵ective and in some cases even detrimental. Therefore, providing FM patients with the correct information about their disorders may help monitoring pharmacological and alternative therapies. At the same time maintaining information will help patients to receive the appropriate medications and therapies [194]. Funding: This research received no external funding. Conflicts of Interest: The author declares no conflict of interest Abbreviations 2-AG 2-ArachidonoylGlycerol AA Arachidonic Acid ACR American College of Rheumatology ACTH Adrenocorticotropic hormone AEA N-arachidonoylethanolamine BDNF Brain-Derived Neurotrophic Factors CB1 Cannabinoid Receptor 1 CB2 Cannabinoid Receptor 2 CBD Cannabidiol CNS Central Nervous System EA Electro-Acupuncture ESS Extent of Somatic Symptoms FIQ FM Impact Questionnaire FIQR FM Impact Questionnaire Revised version FM Fibromyalgia FS Fibromyalgianess Scale GABA Gamma-Aminobutyric Acid Grading of Recommendations, Assessment, GRADE Development, and Evaluation HBOT Hyperbaric Oxygen Therapy ICD-11 International Classification of Diseases IL-1 Interleukin 1 beta IL-6 Interleukin 6 MA Manual Acupuncture PEA Palmitoylethanolamide PFM Primary FM ROS Reactive Oxygen Species SIQ Symptom Impact Questionnaire SFM Secondary FM SNRIs Serotonin and Norepinephrine Reuptake Inhibitors SSRIs Serotonin Selective Reuptake Inhibitors SSS Symptom Severity Scale TCAs Tricyclic Antidepressant TNF↵ Tumor necrosis factor alpha VAS Visual Analog Scale WPI Widespread Pain Index D9-THC Delta 9-tetrahydrocannabinol Int. 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<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

Analyze the development of gene therapies for Metachromatic Leukodystrophy (MLD) and Severe Combined Immunodeficiency (SCID), focusing on the role of lentiviral vectors in their success. Discuss the mechanisms by which Libmeldy and OTL-101 function. Evaluate the long-term clinical efficacy of these therapies, particularly in terms of enzyme activity levels in patients, and the associated impact on survival rates.

Revolutionary gene therapy technique, developed with support from MRC, has led to life-saving treatment for rare genetic childhood disease. Metachromatic leukodystrophy (MLD) is a rare genetic disease that effects children and causes severe damage to the nervous system and organs, resulting in a life expectancy of between just five and eight years. In February 2023, it was announced by the NHS that a 19-month-old baby had become the first child in the UK to receive a life-saving gene therapy treatment for MLD. Previously, it was not possible to stop the disease and treatment was aimed at relieving symptoms using a variety of drugs to ease muscle spasms, treat infections and control seizures. Metachromatic leukodystrophy MLD is caused by an abnormal build-up of substances called sulphatides in the nerve cells, particularly in the white matter of the brain. The build-up takes the place of myelin, the insulating material which is essential for normal transmission of messages between nerves. Normally this build-up is broken down and removed from the body by an enzyme called arylsulphatase A. But in MLD the gene responsible for producing the enzyme is faulty so the normal process cannot occur. Curing the disease requires adding in a good version of the gene for the enzyme by a one-time therapy called ‘Libmeldy’. The therapy works by removing the patient’s stems cells and using lentiviral vectors, a type of virus-based delivery system, to introduce the correct gene, and then injecting the treated cells back into the patient. Gene therapy using lentiviral vectors The development of gene therapy for inherited childhood diseases such as MLD has required long term research funding investment. The Medical Research Council (MRC) has been a major funder of UK gene therapy research for more than 20 years. This includes Professor Gaspar’s studies of rare inherited childhood diseases and lentiviral vectors that have formed the basis of this MLD breakthrough. ‘Bubble boy disease’ Young patient stood with doctor, both are smiling Professor Bobby Gaspar and Teigan, who received treatment for severe combined immunodeficiency. Credit: Great Ormond Street Hospital One of Professor Gaspar’s early successes was the development of a treatment of the rare immune disorder ‘bubble boy disease’. ‘Bubble boy disease’ is so called because affected children have severe combined immunodeficiency (SCID) and are extremely vulnerable to infectious diseases, some of them had become famous for living in a sterile environment. In the most severe forms, children with SCID are unable to fight off even very mild infections and, without treatment, will usually die within the first year of life. Several years of research was done by Bobby Gaspar at Great Ormond Street Hospital and the UCL Institute of Child Health. This focused on developing a gene therapy treatment for a type of SCID known as adenosine deaminase deficiency (ADA), characterised by the lack of an enzyme called adenosine deaminase. Support from MRC’s Developmental Pathway Funding Scheme took this therapy, now called OTL-101, into the clinic and supported the establishment of Orchard Therapeutics. Orchard Therapeutics In 2017, both US and UK drug regulatory authorities granted OTL-101 designations reserved for treatments addressing high unmet need. These developments showed the commercial potential of Professor Gaspar’s work and highlight gene therapy’s ability to improve human health. In April 2018, GlaxoSmithKline signed a strategic agreement to transfer its rare disease gene therapy portfolio to Orchard Therapeutics, strengthening Orchard’s position as a global leader in gene therapy for rare diseases. In May 2021 the researchers followed up 50 patients treated for ADA-SCID with OTL-101, and the results showed 100% survival. Over 95% of the patients had sustained expression of the ADA enzyme showing that the gene therapy was successful, after two to three years following the treatment.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> Analyze the development of gene therapies for Metachromatic Leukodystrophy (MLD) and Severe Combined Immunodeficiency (SCID), focusing on the role of lentiviral vectors in their success. Discuss the mechanisms by which Libmeldy and OTL-101 function. Evaluate the long-term clinical efficacy of these therapies, particularly in terms of enzyme activity levels in patients, and the associated impact on survival rates. <TEXT> Revolutionary gene therapy technique, developed with support from MRC, has led to life-saving treatment for rare genetic childhood disease. Metachromatic leukodystrophy (MLD) is a rare genetic disease that effects children and causes severe damage to the nervous system and organs, resulting in a life expectancy of between just five and eight years. In February 2023, it was announced by the NHS that a 19-month-old baby had become the first child in the UK to receive a life-saving gene therapy treatment for MLD. Previously, it was not possible to stop the disease and treatment was aimed at relieving symptoms using a variety of drugs to ease muscle spasms, treat infections and control seizures. Metachromatic leukodystrophy MLD is caused by an abnormal build-up of substances called sulphatides in the nerve cells, particularly in the white matter of the brain. The build-up takes the place of myelin, the insulating material which is essential for normal transmission of messages between nerves. Normally this build-up is broken down and removed from the body by an enzyme called arylsulphatase A. But in MLD the gene responsible for producing the enzyme is faulty so the normal process cannot occur. Curing the disease requires adding in a good version of the gene for the enzyme by a one-time therapy called ‘Libmeldy’. The therapy works by removing the patient’s stems cells and using lentiviral vectors, a type of virus-based delivery system, to introduce the correct gene, and then injecting the treated cells back into the patient. Gene therapy using lentiviral vectors The development of gene therapy for inherited childhood diseases such as MLD has required long term research funding investment. The Medical Research Council (MRC) has been a major funder of UK gene therapy research for more than 20 years. This includes Professor Gaspar’s studies of rare inherited childhood diseases and lentiviral vectors that have formed the basis of this MLD breakthrough. ‘Bubble boy disease’ Young patient stood with doctor, both are smiling Professor Bobby Gaspar and Teigan, who received treatment for severe combined immunodeficiency. Credit: Great Ormond Street Hospital One of Professor Gaspar’s early successes was the development of a treatment of the rare immune disorder ‘bubble boy disease’. ‘Bubble boy disease’ is so called because affected children have severe combined immunodeficiency (SCID) and are extremely vulnerable to infectious diseases, some of them had become famous for living in a sterile environment. In the most severe forms, children with SCID are unable to fight off even very mild infections and, without treatment, will usually die within the first year of life. Several years of research was done by Bobby Gaspar at Great Ormond Street Hospital and the UCL Institute of Child Health. This focused on developing a gene therapy treatment for a type of SCID known as adenosine deaminase deficiency (ADA), characterised by the lack of an enzyme called adenosine deaminase. Support from MRC’s Developmental Pathway Funding Scheme took this therapy, now called OTL-101, into the clinic and supported the establishment of Orchard Therapeutics. Orchard Therapeutics In 2017, both US and UK drug regulatory authorities granted OTL-101 designations reserved for treatments addressing high unmet need. These developments showed the commercial potential of Professor Gaspar’s work and highlight gene therapy’s ability to improve human health. In April 2018, GlaxoSmithKline signed a strategic agreement to transfer its rare disease gene therapy portfolio to Orchard Therapeutics, strengthening Orchard’s position as a global leader in gene therapy for rare diseases. In May 2021 the researchers followed up 50 patients treated for ADA-SCID with OTL-101, and the results showed 100% survival. Over 95% of the patients had sustained expression of the ADA enzyme showing that the gene therapy was successful, after two to three years following the treatment. https://www.ukri.org/who-we-are/how-we-are-doing/research-outcomes-and-impact/mrc/mrc-funded-discovery-science-underpins-gene-therapy-cures/

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

What does each option's Greek measure and how is it used to determine options pricing?Also, even though it's not a Greek, also include an explanation of implied volatility.

Delta Delta measures how much an option's price can be expected to move for every $1 change in the price of the underlying security or index. For example, a Delta of 0.40 means the option's price will theoretically move $0.40 for every $1 change in the price of the underlying stock or index. As you might guess, this means the higher the Delta, the bigger the price change. Traders often use Delta to predict whether a given option will expire ITM. So, a Delta of 0.40 is taken to mean that at that moment in time, the option has about a 40% chance of being ITM at expiration. This doesn't mean higher-Delta options are always profitable. After all, if you paid a large premium for an option that expires ITM, you might not make any money. You can also think of Delta as the number of shares of the underlying stock the option behaves like. So, a Delta of 0.40 suggests that given a $1 move in the underlying stock, the option will likely gain or lose about the same amount of money as 40 shares of the stock. Call options Call options have a positive Delta that can range from 0.00 to 1.00. At-the-money options usually have a Delta near 0.50. The Delta will increase (and approach 1.00) as the option gets deeper ITM. The Delta of ITM call options will get closer to 1.00 as expiration approaches. The Delta of out-of-the-money call options will get closer to 0.00 as expiration approaches. Put options Put options have a negative Delta that can range from 0.00 to –1.00. At-the-money options usually have a Delta near –0.50. The Delta will decrease (and approach –1.00) as the option gets deeper ITM. The Delta of ITM put options will get closer to –1.00 as expiration approaches. The Delta of out-of-the-money put options will get closer to 0.00 as expiration approaches. Gamma Where Delta is a snapshot in time, Gamma measures the rate of change in an option's Delta over time. If you remember high school physics class, you can think of Delta as speed and Gamma as acceleration. In practice, Gamma is the rate of change in an option's Delta per $1 change in the price of the underlying stock. In the example above, we imagined an option with a Delta of .40. If the underlying stock moves $1 and the option moves $.40 along with it, the option's Delta is no longer 0.40. Why? This $1 move would mean the call option is now even deeper ITM, and so its Delta should move even closer to 1.00. So, let's assume that as a result the Delta is now 0.55. The change in Delta from 0.40 to 0.55 is 0.15—this is the option's Gamma. Because Delta can't exceed 1.00, Gamma decreases as an option gets further ITM and Delta approaches 1.00. After all, there's less room for acceleration as you approach top speed. Theta Theta tells you how much the price of an option should decrease each day as the option nears expiration, if all other factors remain the same. This kind of price erosion over time is known as time decay. Time-value erosion is not linear, meaning the price erosion of at-the-money (ATM), just slightly out-of-the-money, and ITM options generally increases as expiration approaches, while that of far out-of-the-money (OOTM) options generally decreases as expiration approaches. Time-value erosion Source: Schwab Center for Financial Research Vega Vega measures the rate of change in an option's price per one-percentage-point change in the implied volatility of the underlying stock. (There's more on implied volatility below.) While Vega is not a real Greek letter, it is intended to tell you how much an option's price should move when the volatility of the underlying security or index increases or decreases. More about Vega: Volatility is one of the most important factors affecting the value of options. A drop in Vega will typically cause both calls and puts to lose value. An increase in Vega will typically cause both calls and puts to gain value. Neglecting Vega can cause you to potentially overpay when buying options. All other factors being equal, when determining strategy, consider buying options when Vega is below "normal" levels and selling options when Vega is above "normal" levels. One way to determine this is to compare the historical volatility to the implied volatility. Chart studies for both values are available on StreetSmart Edge®. Rho Rho measures the expected change in an option's price per one-percentage-point change in interest rates. It tells you how much the price of an option should rise or fall if the risk-free interest rate (U.S. Treasury-bills)* increases or decreases. More about Rho: As interest rates increase, the value of call options will generally increase. As interest rates increase, the value of put options will usually decrease. For these reasons, call options have positive Rho and put options have negative Rho. Consider a hypothetical stock that's trading exactly at its strike price. If the stock is trading at $25, the 25 calls and the 25 puts would both be exactly at the money. You might see the calls trading at, say, $0.60, while the puts could be trading at $0.50. When interest rates are low, the price difference between puts and calls will be relatively small. If interest rates increase, the gap will get wider—calls will become more expensive and puts will become less so. Rho is generally not a huge factor in the price of an option, but should be considered if prevailing interest rates are expected to change, such as just before a Federal Open Market Committee (FOMC) meeting. Long-Term Equity AnticiPation Securities® (LEAPS®) options are far more sensitive to changes in interest rates than are shorter-term options. Implied volatility: like a Greek Though not actually a Greek, implied volatility is closely related. Implied volatility is a forecast of how volatile an underlying stock is expected to be in the future—but it's strictly theoretical. While it's possible to forecast a stock's future moves by looking at its historical volatility, among other factors, the implied volatility reflected in the price of an option is an inference based on other factors, too, such as upcoming earnings reports, merger and acquisition rumors, pending product launches, etc. Key points to remember: Figuring out exactly how volatile a stock will be at any given time is difficult, but looking at implied volatility can give you a sense of what assumptions market makers are using to determine their quoted bid and ask prices. As such, implied volatility can be a helpful proxy in gauging the market. Higher-than-normal implied volatilities are usually more favorable for options sellers, while lower-than-normal implied volatilities are more favorable for option buyers, because volatility often reverts back to its mean over time. Implied volatility is often provided on options trading platforms because it is typically more useful for traders to know how volatile a market maker thinks a stock will be than to try to estimate it themselves. Implied volatility is usually not consistent for all options of a particular security or index and will generally be lowest for at-the-money and near-the-money options.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. What does each option's Greek measure and how is it used to determine options pricing?Also, even though it's not a Greek, also include an explanation of implied volatility. Delta Delta measures how much an option's price can be expected to move for every $1 change in the price of the underlying security or index. For example, a Delta of 0.40 means the option's price will theoretically move $0.40 for every $1 change in the price of the underlying stock or index. As you might guess, this means the higher the Delta, the bigger the price change. Traders often use Delta to predict whether a given option will expire ITM. So, a Delta of 0.40 is taken to mean that at that moment in time, the option has about a 40% chance of being ITM at expiration. This doesn't mean higher-Delta options are always profitable. After all, if you paid a large premium for an option that expires ITM, you might not make any money. You can also think of Delta as the number of shares of the underlying stock the option behaves like. So, a Delta of 0.40 suggests that given a $1 move in the underlying stock, the option will likely gain or lose about the same amount of money as 40 shares of the stock. Call options Call options have a positive Delta that can range from 0.00 to 1.00. At-the-money options usually have a Delta near 0.50. The Delta will increase (and approach 1.00) as the option gets deeper ITM. The Delta of ITM call options will get closer to 1.00 as expiration approaches. The Delta of out-of-the-money call options will get closer to 0.00 as expiration approaches. Put options Put options have a negative Delta that can range from 0.00 to –1.00. At-the-money options usually have a Delta near –0.50. The Delta will decrease (and approach –1.00) as the option gets deeper ITM. The Delta of ITM put options will get closer to –1.00 as expiration approaches. The Delta of out-of-the-money put options will get closer to 0.00 as expiration approaches. Gamma Where Delta is a snapshot in time, Gamma measures the rate of change in an option's Delta over time. If you remember high school physics class, you can think of Delta as speed and Gamma as acceleration. In practice, Gamma is the rate of change in an option's Delta per $1 change in the price of the underlying stock. In the example above, we imagined an option with a Delta of .40. If the underlying stock moves $1 and the option moves $.40 along with it, the option's Delta is no longer 0.40. Why? This $1 move would mean the call option is now even deeper ITM, and so its Delta should move even closer to 1.00. So, let's assume that as a result the Delta is now 0.55. The change in Delta from 0.40 to 0.55 is 0.15—this is the option's Gamma. Because Delta can't exceed 1.00, Gamma decreases as an option gets further ITM and Delta approaches 1.00. After all, there's less room for acceleration as you approach top speed. Theta Theta tells you how much the price of an option should decrease each day as the option nears expiration, if all other factors remain the same. This kind of price erosion over time is known as time decay. Time-value erosion is not linear, meaning the price erosion of at-the-money (ATM), just slightly out-of-the-money, and ITM options generally increases as expiration approaches, while that of far out-of-the-money (OOTM) options generally decreases as expiration approaches. Time-value erosion Source: Schwab Center for Financial Research Vega Vega measures the rate of change in an option's price per one-percentage-point change in the implied volatility of the underlying stock. (There's more on implied volatility below.) While Vega is not a real Greek letter, it is intended to tell you how much an option's price should move when the volatility of the underlying security or index increases or decreases. More about Vega: Volatility is one of the most important factors affecting the value of options. A drop in Vega will typically cause both calls and puts to lose value. An increase in Vega will typically cause both calls and puts to gain value. Neglecting Vega can cause you to potentially overpay when buying options. All other factors being equal, when determining strategy, consider buying options when Vega is below "normal" levels and selling options when Vega is above "normal" levels. One way to determine this is to compare the historical volatility to the implied volatility. Chart studies for both values are available on StreetSmart Edge®. Rho Rho measures the expected change in an option's price per one-percentage-point change in interest rates. It tells you how much the price of an option should rise or fall if the risk-free interest rate (U.S. Treasury-bills)* increases or decreases. More about Rho: As interest rates increase, the value of call options will generally increase. As interest rates increase, the value of put options will usually decrease. For these reasons, call options have positive Rho and put options have negative Rho. Consider a hypothetical stock that's trading exactly at its strike price. If the stock is trading at $25, the 25 calls and the 25 puts would both be exactly at the money. You might see the calls trading at, say, $0.60, while the puts could be trading at $0.50. When interest rates are low, the price difference between puts and calls will be relatively small. If interest rates increase, the gap will get wider—calls will become more expensive and puts will become less so. Rho is generally not a huge factor in the price of an option, but should be considered if prevailing interest rates are expected to change, such as just before a Federal Open Market Committee (FOMC) meeting. Long-Term Equity AnticiPation Securities® (LEAPS®) options are far more sensitive to changes in interest rates than are shorter-term options. Implied volatility: like a Greek Though not actually a Greek, implied volatility is closely related. Implied volatility is a forecast of how volatile an underlying stock is expected to be in the future—but it's strictly theoretical. While it's possible to forecast a stock's future moves by looking at its historical volatility, among other factors, the implied volatility reflected in the price of an option is an inference based on other factors, too, such as upcoming earnings reports, merger and acquisition rumors, pending product launches, etc. Key points to remember: Figuring out exactly how volatile a stock will be at any given time is difficult, but looking at implied volatility can give you a sense of what assumptions market makers are using to determine their quoted bid and ask prices. As such, implied volatility can be a helpful proxy in gauging the market. Higher-than-normal implied volatilities are usually more favorable for options sellers, while lower-than-normal implied volatilities are more favorable for option buyers, because volatility often reverts back to its mean over time. Implied volatility is often provided on options trading platforms because it is typically more useful for traders to know how volatile a market maker thinks a stock will be than to try to estimate it themselves. Implied volatility is usually not consistent for all options of a particular security or index and will generally be lowest for at-the-money and near-the-money options. https://www.schwab.com/learn/story/get-to-know-option-greeks

Your responses are always thorough covering all bases to ensure the user has all the information they need, but you find a happy medium to not be to wordy. You always explain how you came to each conclusion and you only use the text that is provided to you to answer questions.

What acronyms are mentioned?

AI technologies, including GenAI tools, have many potential benefits, such as accelerating and providing insights into data processing, augmenting human decisionmaking, and optimizing performance for complex systems and tasks. GenAI tools, for example, are increasingly capable of performing a broad range of tasks, such as text analysis, image generation, and speech recognition. However, AI systems may perpetuate or amplify biases in the datasets on which they are trained; may not yet be able to fully explain their decisionmaking; and often depend on such vast amounts of data and other resources that they are not widely accessible for research, development, and commercialization beyond a handful of technology companies. Numerous federal laws on AI have been enacted over the past few Congresses, either as standalone legislation or as AIfocused provisions in broader acts. These include the expansive National Artificial Intelligence Initiative Act of 2020 (Division E of P.L. 116-283), which included the establishment of an American AI Initiative and direction for AI research, development, and evaluation activities at federal science agencies. Additional acts have directed certain agencies to undertake activities to guide AI programs and policies across the federal government (e.g., the AI in Government Act of 2020, P.L. 116- 260; and the Advancing American AI Act, Subtitle B of P.L. 117-263). In the 117th Congress, at least 75 bills were introduced that either focused on AI and ML or had AI/ML-focused provisions. Six of those were enacted. In the 118th Congress, as of June 2023, at least 40 bills had been introduced that either focused on AI/ML or contained AI/ML-focused provisions, and none has been enacted. Collectively, bills in the 118th Congress address a range of topics, including federal government oversight of AI; training for federal employees; disclosure of AI use; export controls; usespecific prohibitions; and support for the use of AI in particular sectors, such as cybersecurity, weather modeling, wildfire detection, precision agriculture, and airport safety. AI technologies have potential applications across a wide range of sectors. A selection of broad, crosscutting issues with application-specific examples of ongoing congressional interest are discussed in the CRS report Artificial Intelligence: Background, Selected Issues, and Policy Considerations. 17 Those issues and examples include implications for the U.S. workforce, international competition and federal investment in AI R&D, standards development, and ethical AI—including questions about bias, fairness, and algorithm transparency (for example, in criminal justice applications). In addition to those issues and applications, three areas of potential use that may be of growing interest to Congress—particularly in light of the advances in, and widespread availability of, GenAI tools—are health care, education, and national security. In other parts of the federal government, experts have asserted a need to understand the impacts and future directions of AI applications in these areas. For example, the chief AI officer at the Department of Health and Human Services, Greg Singleton, at a June 2023 Health Innovation Summit discussed “the role that AI will play in healthcare, as well as the importance of regulations.” 18 A May 2023 Department of Education report, Artificial Intelligence and the Future of Teaching and Learning, describes the rising interest in AI in education and highlights reasons to address AI in education now.19 And the 2023 Annual Threat Assessment of the U.S. Intelligence Community states, “New technologies—particularly in the fields of AI and biotechnology—are being developed and are proliferating faster than companies and governments can shape norms, protect privacy, and prevent dangerous outcomes.”20 This section will discuss some of the potential benefits and concerns with the use of AI technologies in these sectors. Federal laws addressing AI or including AI-focused provisions have been enacted over the past few Congresses. Arguably the most expansive law was the National Artificial Intelligence Initiative (NAII) Act of 2020 (Division E of the William M. (Mac) Thornberry National Defense Authorization Act [NDAA] of FY2021, P.L. 116-283). The NAII Act included sections • codifying the establishment of an American AI Initiative, • establishing a National Artificial Intelligence Initiative Office to support federal AI activities, • establishing an interagency committee at the Office of Science and Technology Policy to coordinate federal programs and activities in support of the NAII, and • establishing a National AI Advisory Committee. The NAII Act further directed AI activities at the National Science Foundation (NSF), National Institute of Standards and Technology (NIST),40 National Oceanic and Atmospheric Administration, and Department of Energy. Specific provisions include mandating (1) NSF support for a network of National AI Research Institutes; (2) a National Academies of Sciences, Engineering, and Medicine study on the current and future impact of AI on the U.S. workforce across sectors;41 and (3) a task force to investigate the feasibility of, and plan for, a National AI Research Resource.42 Individual agencies—including the General Services Administration (GSA), the Office of Management and Budget (OMB), and the Office of Personnel Management (OPM)—have also been statutorily directed to undertake activities to support the use of AI across the federal government: • GSA. The AI in Government Act of 2020 (AGA, Division U, Title I, of the Consolidated Appropriations Act, 2021, P.L. 116-260) created within GSA an AI Center of Excellence to facilitate the adoption of AI technologies in the federal government and collect and publicly publish information regarding federal programs, pilots, and other initiatives.43 • OMB. The AGA required OMB to issue a memorandum to federal agencies regarding the development of AI policies; approaches for removing barriers to using AI technologies; and best practices for identifying, assessing, and mitigating any discriminatory impact or bias and any unintended consequences of using AI. The Advancing American AI Act (Subtitle B of the James M. Inhofe National Defense Authorization Act for Fiscal Year 2023, P.L. 117-263) required OMB to (1) incorporate additional considerations when developing guidance for the use of AI in the federal government; (2) develop an initial means to ensure that contracts for acquiring AI address privacy, civil rights and liberties, and the protection of government data and information; (3) require the head of each federal agency (except DOD) to prepare and maintain an inventory of current and planned AI use cases; and (4) lead a pilot program to initiate four new AI use case applications to support interagency or intra-agency modernization initiatives. Additionally, the AI Training Act (P.L. 117-207) required OMB to establish an AI training program for the acquisition workforce of executive agencies. • OPM. The AGA required OPM to establish or update an occupational job series to include positions with primary duties in AI and to estimate current and future numbers of federal employment positions related to AI at each agency. NDAAs have also included provisions focused on AI in the defense, national security, and intelligence communities each year beginning with the FY2019 John S. McCain NDAA, which included the first definition of AI in federal statute.44 These provisions have included a focus on AI development, acquisition, and policies; AI data repositories; recruiting and retaining personnel in AI; and implementation of recommendations from the 2021 final report of the National Security Commission on AI.45 Additionally, some enacted legislation has focused on AI R&D or the use of AI in particular federal programs. For example: • The CHIPS and Science Act (P.L. 117-167) included numerous AI-related provisions directing the Department of Energy, NIST, and NSF to support AI and ML R&D activities and the development of technical standards and guidelines related to safe and trustworthy AI systems. NSF was further directed to (1) evaluate the establishment of an AI scholarship-for-service program to recruit and train AI professionals to support AI work in federal, state, local, and tribal governments; and (2) study AI research capacity at U.S. institutions of higher education.

Your responses are always thorough covering all bases to ensure the user has all the information they need, but you find a happy medium to not be to wordy. You always explain how you came to each conclusion and you only use the text that is provided to you to answer questions. AI technologies, including GenAI tools, have many potential benefits, such as accelerating and providing insights into data processing, augmenting human decisionmaking, and optimizing performance for complex systems and tasks. GenAI tools, for example, are increasingly capable of performing a broad range of tasks, such as text analysis, image generation, and speech recognition. However, AI systems may perpetuate or amplify biases in the datasets on which they are trained; may not yet be able to fully explain their decisionmaking; and often depend on such vast amounts of data and other resources that they are not widely accessible for research, development, and commercialization beyond a handful of technology companies. Numerous federal laws on AI have been enacted over the past few Congresses, either as standalone legislation or as AIfocused provisions in broader acts. These include the expansive National Artificial Intelligence Initiative Act of 2020 (Division E of P.L. 116-283), which included the establishment of an American AI Initiative and direction for AI research, development, and evaluation activities at federal science agencies. Additional acts have directed certain agencies to undertake activities to guide AI programs and policies across the federal government (e.g., the AI in Government Act of 2020, P.L. 116- 260; and the Advancing American AI Act, Subtitle B of P.L. 117-263). In the 117th Congress, at least 75 bills were introduced that either focused on AI and ML or had AI/ML-focused provisions. Six of those were enacted. In the 118th Congress, as of June 2023, at least 40 bills had been introduced that either focused on AI/ML or contained AI/ML-focused provisions, and none has been enacted. Collectively, bills in the 118th Congress address a range of topics, including federal government oversight of AI; training for federal employees; disclosure of AI use; export controls; usespecific prohibitions; and support for the use of AI in particular sectors, such as cybersecurity, weather modeling, wildfire detection, precision agriculture, and airport safety. AI technologies have potential applications across a wide range of sectors. A selection of broad, crosscutting issues with application-specific examples of ongoing congressional interest are discussed in the CRS report Artificial Intelligence: Background, Selected Issues, and Policy Considerations. 17 Those issues and examples include implications for the U.S. workforce, international competition and federal investment in AI R&D, standards development, and ethical AI—including questions about bias, fairness, and algorithm transparency (for example, in criminal justice applications). In addition to those issues and applications, three areas of potential use that may be of growing interest to Congress—particularly in light of the advances in, and widespread availability of, GenAI tools—are health care, education, and national security. In other parts of the federal government, experts have asserted a need to understand the impacts and future directions of AI applications in these areas. For example, the chief AI officer at the Department of Health and Human Services, Greg Singleton, at a June 2023 Health Innovation Summit discussed “the role that AI will play in healthcare, as well as the importance of regulations.” 18 A May 2023 Department of Education report, Artificial Intelligence and the Future of Teaching and Learning, describes the rising interest in AI in education and highlights reasons to address AI in education now.19 And the 2023 Annual Threat Assessment of the U.S. Intelligence Community states, “New technologies—particularly in the fields of AI and biotechnology—are being developed and are proliferating faster than companies and governments can shape norms, protect privacy, and prevent dangerous outcomes.”20 This section will discuss some of the potential benefits and concerns with the use of AI technologies in these sectors. Federal laws addressing AI or including AI-focused provisions have been enacted over the past few Congresses. Arguably the most expansive law was the National Artificial Intelligence Initiative (NAII) Act of 2020 (Division E of the William M. (Mac) Thornberry National Defense Authorization Act [NDAA] of FY2021, P.L. 116-283). The NAII Act included sections • codifying the establishment of an American AI Initiative, • establishing a National Artificial Intelligence Initiative Office to support federal AI activities, • establishing an interagency committee at the Office of Science and Technology Policy to coordinate federal programs and activities in support of the NAII, and • establishing a National AI Advisory Committee. The NAII Act further directed AI activities at the National Science Foundation (NSF), National Institute of Standards and Technology (NIST),40 National Oceanic and Atmospheric Administration, and Department of Energy. Specific provisions include mandating (1) NSF support for a network of National AI Research Institutes; (2) a National Academies of Sciences, Engineering, and Medicine study on the current and future impact of AI on the U.S. workforce across sectors;41 and (3) a task force to investigate the feasibility of, and plan for, a National AI Research Resource.42 Individual agencies—including the General Services Administration (GSA), the Office of Management and Budget (OMB), and the Office of Personnel Management (OPM)—have also been statutorily directed to undertake activities to support the use of AI across the federal government: • GSA. The AI in Government Act of 2020 (AGA, Division U, Title I, of the Consolidated Appropriations Act, 2021, P.L. 116-260) created within GSA an AI Center of Excellence to facilitate the adoption of AI technologies in the federal government and collect and publicly publish information regarding federal programs, pilots, and other initiatives.43 • OMB. The AGA required OMB to issue a memorandum to federal agencies regarding the development of AI policies; approaches for removing barriers to using AI technologies; and best practices for identifying, assessing, and mitigating any discriminatory impact or bias and any unintended consequences of using AI. The Advancing American AI Act (Subtitle B of the James M. Inhofe National Defense Authorization Act for Fiscal Year 2023, P.L. 117-263) required OMB to (1) incorporate additional considerations when developing guidance for the use of AI in the federal government; (2) develop an initial means to ensure that contracts for acquiring AI address privacy, civil rights and liberties, and the protection of government data and information; (3) require the head of each federal agency (except DOD) to prepare and maintain an inventory of current and planned AI use cases; and (4) lead a pilot program to initiate four new AI use case applications to support interagency or intra-agency modernization initiatives. Additionally, the AI Training Act (P.L. 117-207) required OMB to establish an AI training program for the acquisition workforce of executive agencies. • OPM. The AGA required OPM to establish or update an occupational job series to include positions with primary duties in AI and to estimate current and future numbers of federal employment positions related to AI at each agency. NDAAs have also included provisions focused on AI in the defense, national security, and intelligence communities each year beginning with the FY2019 John S. McCain NDAA, which included the first definition of AI in federal statute.44 These provisions have included a focus on AI development, acquisition, and policies; AI data repositories; recruiting and retaining personnel in AI; and implementation of recommendations from the 2021 final report of the National Security Commission on AI.45 Additionally, some enacted legislation has focused on AI R&D or the use of AI in particular federal programs. For example: • The CHIPS and Science Act (P.L. 117-167) included numerous AI-related provisions directing the Department of Energy, NIST, and NSF to support AI and ML R&D activities and the development of technical standards and guidelines related to safe and trustworthy AI systems. NSF was further directed to (1) evaluate the establishment of an AI scholarship-for-service program to recruit and train AI professionals to support AI work in federal, state, local, and tribal governments; and (2) study AI research capacity at U.S. institutions of higher education. What acronyms are mentioned?

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

My daughter has just been tested and we have learned she has a severe allergy to tree nuts. I'm freaking out. We have been given an epipen and using it scares me too. How and where do I inject it? Are there certain places it would be harmful? What are the signs of anaphylaxis? Also, what are the potential side effects of an EpiPen?

What is EpiPen? EpiPen and Epipen Jr are used to treat life-threatening allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs, and other allergens, and also treat exercise-induced anaphylaxis. EpiPen Auto-Injectors reduce wheezing and improve low blood pressure, hives, severe low blood pressure, and other symptoms of an allergic reaction. EpiPen contains epinephrine from a class of medications called sympathomimetic agents which works by relaxing the muscles in the airways and tightening the blood vessels. Epinephrine is also called adrenaline. EpiPen Auto-Injectors are hand-held devices that automatically inject a measured dose of medicine. EpiPen Auto-Injectors make it easier to give epinephrine in an emergency when anaphylaxis occurs. Anaphylaxis can be life-threatening and can happen within minutes and, if untreated, can lead to death. Each EpiPen or EpiPen Jr auto-injector can be used only 1 time (single-use). What is anaphylaxis? Anaphylaxis is a life-threatening allergic reaction to insect stings or bites, foods, drugs, exercise-induced anaphylaxis, and other allergens. Sometimes the cause of anaphylaxis is unknown. EpiPen and Epi-pen Jr Auto-Injectors reduce wheezing and improve low blood pressure, hives, severe low blood pressure, and other symptoms of an allergic reaction. Anaphylaxis can happen within minutes and, left untreated, can lead to death Symptoms of anaphylaxis may include: trouble breathing wheezing hoarseness (changes in the way your voice sounds) hives (raised reddened rash that may itch) severe itching swelling of your face, lips, mouth, or tongue skin rash, redness, or swelling fast heartbeat weak pulse feeling very anxious confusion stomach pain losing control of urine or bowel movements (incontinence) diarrhea or stomach cramps dizziness, fainting, or “passing out” (unconsciousness). Anaphylaxis is treated with epinephrine injections such as Epipen, but you must seek emergency medical treatment right away, even if you have used the EpiPen or EpiPen Jr auto-injector. Seek emergency medical attention even after you use EpiPen to treat a severe allergic reaction. You will need to receive further treatment and observation. Before using EpiPen a second time, tell your doctor if your first injection caused a serious side effect such as increased breathing difficulty, or dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure). It is recommended that patients at risk of anaphylaxis carry 2 auto-injectors in case the first auto-injector is activated before the dose can be given, or you need a second dose. You may not know when anaphylaxis will happen. Talk to your healthcare provider if you need more auto-injectors to keep at work, school, or other locations. Make sure your family members, caregivers, and others where you keep your EpiPen or EpiPen Jr auto-injectors and they know how to use it before you need it. You may be unable to speak in an allergic emergency. A “trainer pen” is available to teach and practice giving an injection. The trainer pen contains no medicine and no needle. The EpiPen Auto-Injector device is a disposable single-use system. An Auto-Injector can only be used one time. You may need to use a second EpiPen auto-injector if symptoms continue or come back while you wait for emergency help or if the first auto-injector is activated before the dose can be given. Do not remove the safety cap until you are ready to use the Auto-Injector. Never put your fingers over the injector tip after the safety cap has been removed. Do not give this medicine to a child without medical advice. EpiPen is injected into the skin or muscle of your outer thigh. In an emergency, this injection can be given through your clothing. Do not inject into a vein or into the buttocks, fingers, toes, hands or feet. To use an EpiPen Auto-Injector: Form a fist around the Auto-Injector with the orange end pointing down. Pull the blue safety top straight up and away from the auto-injector. Place the orange tip against the fleshy portion of the outer thigh. You may give the injection directly through your clothing. Do not put your thumb over the end of the unit. Hold the leg firmly when giving this injection to a child or infant. Push the Auto-Injector firmly against the outer thigh and hold the EpiPen or Epi-pen Jr auto-injector down firmly on the middle of the outer thigh (upper leg) for at least 3 full seconds. If you do not hold it in place long enough, the EpiPen or EpiPen Jr auto-injector might not have time to deliver the correct dose of medicine. Remove the Auto-Injector from the thigh. The EpiPen or EpiPen Jr auto-injector has been activated when the blue safety top is removed and a “pop” is heard, the orange needle end of the auto-injector is extended, or the medicine viewing window is blocked. Carefully re-insert the used device needle-first into the carrying tube. Re-cap the tube and take it with you to the emergency room so that anyone who treats you will know how much epinephrine you have received. If you accidentally inject yourself while giving EpiPen to another person you must seek medical attention. Accidental injection into fingers, hands or feet may cause a loss of blood flow to these areas. If an accidental injection happens, go immediately to the nearest emergency room. Use an Auto-Injector only once, then throw away in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets. Your medicine may also come with a "trainer pen." The trainer pen contains no medicine and no needle. It is only for non-emergency use to practice giving yourself an injection. Dosing information Usual Epipen dose patients over 30kg (66 lbs): EpiPen 0.3 mg. Usual Epipen dose patients 15 to 30 kg (33 lbs to 66 lbs): EpiPen Jr 0.15 mg. Inject intramuscularly or subcutaneously into the outer thigh, through clothing if necessary. Each device is a single-dose injection. Epipen is available as: EpiPen Auto-Injector 0.3 mg (0.3 mg/0.3 mL) single-dose pre-filled auto-injector EpiPen Jr Auto-Injector: 0.15 mg (0.15 mg/0.3 mL) single-dose pre-filled auto-injectorkilograms). To make sure this medicine is safe for you, tell your doctor if you have ever had: heart disease or high blood pressure; asthma; Parkinson's disease; depression or mental illness; a thyroid disorder; or diabetes. Pregnancy and breastfeeding Having an allergic reaction while pregnant or nursing could harm both mother and baby. What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include numbness or weakness, severe headache, blurred vision, pounding in your neck or ears, sweating, chills, chest pain, fast or slow heartbeats, severe shortness of breath, or cough with foamy mucus. What should I avoid while using EpiPen? Do not inject EpiPen into a vein or into the muscles of your buttocks, or it may not work as well. Inject it only into the fleshy outer portion of the thigh. EpiPen side effects Before using EpiPen, tell your doctor if any past use has caused an allergic reaction to get worse. Call your doctor at once if you notice pain, swelling, warmth, redness, or other signs of infection around the area where you gave an injection. Common EpiPen side effects may include: breathing problems; fast, irregular, or pounding heartbeats; pale skin, sweating; nausea and vomiting; dizziness; weakness or tremors; headache; or feeling restless, fearful, nervous, anxious, or excited. This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. My daughter has just been tested and we have learned she has a severe allergy to tree nuts. I'm freaking out. We have been given an epipen and using it scares me too. How and where do I inject it? Are there certain places it would be harmful? What are the signs of anaphylaxis? Also, what are the potential side effects of an EpiPen? What is EpiPen? EpiPen and Epipen Jr are used to treat life-threatening allergic reactions (anaphylaxis) to insect stings or bites, foods, drugs, and other allergens, and also treat exercise-induced anaphylaxis. EpiPen Auto-Injectors reduce wheezing and improve low blood pressure, hives, severe low blood pressure, and other symptoms of an allergic reaction. EpiPen contains epinephrine from a class of medications called sympathomimetic agents which works by relaxing the muscles in the airways and tightening the blood vessels. Epinephrine is also called adrenaline. EpiPen Auto-Injectors are hand-held devices that automatically inject a measured dose of medicine. EpiPen Auto-Injectors make it easier to give epinephrine in an emergency when anaphylaxis occurs. Anaphylaxis can be life-threatening and can happen within minutes and, if untreated, can lead to death. Each EpiPen or EpiPen Jr auto-injector can be used only 1 time (single-use). What is anaphylaxis? Anaphylaxis is a life-threatening allergic reaction to insect stings or bites, foods, drugs, exercise-induced anaphylaxis, and other allergens. Sometimes the cause of anaphylaxis is unknown. EpiPen and Epi-pen Jr Auto-Injectors reduce wheezing and improve low blood pressure, hives, severe low blood pressure, and other symptoms of an allergic reaction. Anaphylaxis can happen within minutes and, left untreated, can lead to death Symptoms of anaphylaxis may include: trouble breathing wheezing hoarseness (changes in the way your voice sounds) hives (raised reddened rash that may itch) severe itching swelling of your face, lips, mouth, or tongue skin rash, redness, or swelling fast heartbeat weak pulse feeling very anxious confusion stomach pain losing control of urine or bowel movements (incontinence) diarrhea or stomach cramps dizziness, fainting, or “passing out” (unconsciousness). Anaphylaxis is treated with epinephrine injections such as Epipen, but you must seek emergency medical treatment right away, even if you have used the EpiPen or EpiPen Jr auto-injector. Seek emergency medical attention even after you use EpiPen to treat a severe allergic reaction. You will need to receive further treatment and observation. Before using EpiPen a second time, tell your doctor if your first injection caused a serious side effect such as increased breathing difficulty, or dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure). It is recommended that patients at risk of anaphylaxis carry 2 auto-injectors in case the first auto-injector is activated before the dose can be given, or you need a second dose. You may not know when anaphylaxis will happen. Talk to your healthcare provider if you need more auto-injectors to keep at work, school, or other locations. Make sure your family members, caregivers, and others where you keep your EpiPen or EpiPen Jr auto-injectors and they know how to use it before you need it. You may be unable to speak in an allergic emergency. A “trainer pen” is available to teach and practice giving an injection. The trainer pen contains no medicine and no needle. The EpiPen Auto-Injector device is a disposable single-use system. An Auto-Injector can only be used one time. You may need to use a second EpiPen auto-injector if symptoms continue or come back while you wait for emergency help or if the first auto-injector is activated before the dose can be given. Do not remove the safety cap until you are ready to use the Auto-Injector. Never put your fingers over the injector tip after the safety cap has been removed. Do not give this medicine to a child without medical advice. EpiPen is injected into the skin or muscle of your outer thigh. In an emergency, this injection can be given through your clothing. Do not inject into a vein or into the buttocks, fingers, toes, hands or feet. To use an EpiPen Auto-Injector: Form a fist around the Auto-Injector with the orange end pointing down. Pull the blue safety top straight up and away from the auto-injector. Place the orange tip against the fleshy portion of the outer thigh. You may give the injection directly through your clothing. Do not put your thumb over the end of the unit. Hold the leg firmly when giving this injection to a child or infant. Push the Auto-Injector firmly against the outer thigh and hold the EpiPen or Epi-pen Jr auto-injector down firmly on the middle of the outer thigh (upper leg) for at least 3 full seconds. If you do not hold it in place long enough, the EpiPen or EpiPen Jr auto-injector might not have time to deliver the correct dose of medicine. Remove the Auto-Injector from the thigh. The EpiPen or EpiPen Jr auto-injector has been activated when the blue safety top is removed and a “pop” is heard, the orange needle end of the auto-injector is extended, or the medicine viewing window is blocked. Carefully re-insert the used device needle-first into the carrying tube. Re-cap the tube and take it with you to the emergency room so that anyone who treats you will know how much epinephrine you have received. If you accidentally inject yourself while giving EpiPen to another person you must seek medical attention. Accidental injection into fingers, hands or feet may cause a loss of blood flow to these areas. If an accidental injection happens, go immediately to the nearest emergency room. Use an Auto-Injector only once, then throw away in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets. Your medicine may also come with a "trainer pen." The trainer pen contains no medicine and no needle. It is only for non-emergency use to practice giving yourself an injection. Dosing information Usual Epipen dose patients over 30kg (66 lbs): EpiPen 0.3 mg. Usual Epipen dose patients 15 to 30 kg (33 lbs to 66 lbs): EpiPen Jr 0.15 mg. Inject intramuscularly or subcutaneously into the outer thigh, through clothing if necessary. Each device is a single-dose injection. Epipen is available as: EpiPen Auto-Injector 0.3 mg (0.3 mg/0.3 mL) single-dose pre-filled auto-injector EpiPen Jr Auto-Injector: 0.15 mg (0.15 mg/0.3 mL) single-dose pre-filled auto-injectorkilograms). To make sure this medicine is safe for you, tell your doctor if you have ever had: heart disease or high blood pressure; asthma; Parkinson's disease; depression or mental illness; a thyroid disorder; or diabetes. Pregnancy and breastfeeding Having an allergic reaction while pregnant or nursing could harm both mother and baby. What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include numbness or weakness, severe headache, blurred vision, pounding in your neck or ears, sweating, chills, chest pain, fast or slow heartbeats, severe shortness of breath, or cough with foamy mucus. What should I avoid while using EpiPen? Do not inject EpiPen into a vein or into the muscles of your buttocks, or it may not work as well. Inject it only into the fleshy outer portion of the thigh. EpiPen side effects Before using EpiPen, tell your doctor if any past use has caused an allergic reaction to get worse. Call your doctor at once if you notice pain, swelling, warmth, redness, or other signs of infection around the area where you gave an injection. Common EpiPen side effects may include: breathing problems; fast, irregular, or pounding heartbeats; pale skin, sweating; nausea and vomiting; dizziness; weakness or tremors; headache; or feeling restless, fearful, nervous, anxious, or excited. This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. https://www.drugs.com/epipen-auto-injector.html

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. [user request] [context document]

In what specific use cases should someone prefer o1-mini or o1-preview. Use evidence from the reference text wherever possible, including the name of the metric and the results.

OpenAI o1-mini Advancing cost-efficient reasoning. Contributions We're releasing OpenAI o1-mini, a cost-efficient reasoning model. o1-mini excels at STEM, especially math and coding—nearly matching the performance of OpenAI o1 on evaluation benchmarks such as AIME and Codeforces. We expect o1-mini will be a faster, cost-effective model for applications that require reasoning without broad world knowledge. Today, we are launching o1-mini to tier 5 API users(opens in a new window) at a cost that is 80% cheaper than OpenAI o1-preview. ChatGPT Plus, Team, Enterprise, and Edu users can use o1-mini as an alternative to o1-preview, with higher rate limits and lower latency (see Model Speed). Optimized for STEM Reasoning Large language models such as o1 are pre-trained on vast text datasets. While these high-capacity models have broad world knowledge, they can be expensive and slow for real-world applications. In contrast, o1-mini is a smaller model optimized for STEM reasoning during pretraining. After training with the same high-compute reinforcement learning (RL) pipeline as o1, o1-mini achieves comparable performance on many useful reasoning tasks, while being significantly more cost efficient. When evaluated on benchmarks requiring intelligence and reasoning, o1-mini performs well compared to o1-preview and o1. However, o1-mini performs worse on tasks requiring non-STEM factual knowledge (see Limitations). Math Performance vs Inference Cost GPT-4o GPT-4o mini o1-preview o1-mini o1 0 10 20 30 40 50 60 70 80 90 100 Inference Cost (%) 0% 20% 40% 60% 80% AIME Mathematics: In the high school AIME math competition, o1-mini (70.0%) is competitive with o1 (74.4%)–while being significantly cheaper–and outperforms o1-preview (44.6%). o1-mini’s score (about 11/15 questions) places it in approximately the top 500 US high-school students. Coding: On the Codeforces competition website, o1-mini achieves 1650 Elo, which is again competitive with o1 (1673) and higher than o1-preview (1258). This Elo score puts the model at approximately the 86th percentile of programmers who compete on the Codeforces platform. o1-mini also performs well on the HumanEval coding benchmark and high-school level cybersecurity capture the flag challenges (CTFs). Codeforces 1650 1258 900 o1-mini o1-preview GPT-4o 0 200 400 600 800 1,000 1,200 1,400 1,600 1,800 Elo HumanEval 92.4% 92.4% 90.2% o1-mini o1-preview GPT-4o 0 10 20 30 40 50 60 70 80 90 100 Accuracy Cybersecurity CTFs 28.7% 43.0% 20.0% o1-mini o1-preview GPT-4o 0 5 10 15 20 25 30 35 40 45 Accuracy (Pass@12) STEM: On some academic benchmarks requiring reasoning, such as GPQA (science) and MATH-500, o1-mini outperforms GPT-4o. o1-mini does not perform as well as GPT-4o on tasks such as MMLU and lags behind o1-preview on GPQA due to its lack of broad world knowledge. MMLU 0-shot CoT 88.7% 85.2% 90.8% 92.3% GPT-4o o1-mini o1-preview o1 0 10 20 30 40 50 60 70 80 90 100 GPQA Diamond, 0-shot CoT 53.6% 60.0% 73.3% 77.3% GPT-4o o1-mini o1-preview o1 0 10 20 30 40 50 60 70 80 90 100 MATH-500 0-shot CoT 60.3% 90.0% 85.5% 94.8% GPT-4o o1-mini o1-preview o1 0 10 20 30 40 50 60 70 80 90 100 Human preference evaluation: We had human raters compare o1-mini to GPT-4o on challenging, open-ended prompts in various domains, using the same methodology as our o1-preview vs GPT-4o comparison. Similar to o1-preview, o1-mini is preferred to GPT-4o in reasoning-heavy domains, but is not preferred to GPT-4o in language-focused domains. Human preference evaluation vs chatgpt-4o-latest o1-preview o1-mini Personal Writing Editing Text Computer Programming Data Analysis Mathematical Calculation 0 20 40 60 80 100 Win Rate vs GPT-4o (%) Domain Model Speed As a concrete example, we compared responses from GPT-4o, o1-mini, and o1-preview on a word reasoning question. While GPT-4o did not answer correctly, both o1-mini and o1-preview did, and o1-mini reached the answer around 3-5x faster. Chat speed comparison Safety o1-mini is trained using the same alignment and safety techniques as o1-preview. The model has 59% higher jailbreak robustness on an internal version of the StrongREJECT dataset compared to GPT-4o. Before deployment, we carefully assessed the safety risks of o1-mini using the same approach to preparedness, external red-teaming, and safety evaluations as o1-preview. We are publishing the detailed results from these evaluations in the accompanying system card. Metric GPT-4o o1-mini % Safe completions refusal on harmful prompts (standard) 0.99 0.99 % Safe completions on harmful prompts (Challenging: jailbreaks & edge cases) 0.714 0.932 % Compliance on benign edge cases (“not over-refusal”) 0.91 0.923 [email protected] StrongREJECT jailbreak eval (Souly et al. 2024(opens in a new window)) 0.22 0.83 Human sourced jailbreak eval 0.77 0.95 Limitations and What’s Next Due to its specialization on STEM reasoning capabilities, o1-mini’s factual knowledge on non-STEM topics such as dates, biographies, and trivia is comparable to small LLMs such as GPT-4o mini. We will improve these limitations in future versions, as well as experiment with extending the model to other modalities and specialities outside of STEM.

Answer the question based solely on the information provided in the passage. Do not use any external knowledge or resources. In what specific use cases should someone prefer o1-mini or o1-preview. Use evidence from the reference text wherever possible, including the name of the metric and the results. OpenAI o1-mini Advancing cost-efficient reasoning. Contributions We're releasing OpenAI o1-mini, a cost-efficient reasoning model. o1-mini excels at STEM, especially math and coding—nearly matching the performance of OpenAI o1 on evaluation benchmarks such as AIME and Codeforces. We expect o1-mini will be a faster, cost-effective model for applications that require reasoning without broad world knowledge. Today, we are launching o1-mini to tier 5 API users(opens in a new window) at a cost that is 80% cheaper than OpenAI o1-preview. ChatGPT Plus, Team, Enterprise, and Edu users can use o1-mini as an alternative to o1-preview, with higher rate limits and lower latency (see Model Speed). Optimized for STEM Reasoning Large language models such as o1 are pre-trained on vast text datasets. While these high-capacity models have broad world knowledge, they can be expensive and slow for real-world applications. In contrast, o1-mini is a smaller model optimized for STEM reasoning during pretraining. After training with the same high-compute reinforcement learning (RL) pipeline as o1, o1-mini achieves comparable performance on many useful reasoning tasks, while being significantly more cost efficient. When evaluated on benchmarks requiring intelligence and reasoning, o1-mini performs well compared to o1-preview and o1. However, o1-mini performs worse on tasks requiring non-STEM factual knowledge (see Limitations). Math Performance vs Inference Cost GPT-4o GPT-4o mini o1-preview o1-mini o1 0 10 20 30 40 50 60 70 80 90 100 Inference Cost (%) 0% 20% 40% 60% 80% AIME Mathematics: In the high school AIME math competition, o1-mini (70.0%) is competitive with o1 (74.4%)–while being significantly cheaper–and outperforms o1-preview (44.6%). o1-mini’s score (about 11/15 questions) places it in approximately the top 500 US high-school students. Coding: On the Codeforces competition website, o1-mini achieves 1650 Elo, which is again competitive with o1 (1673) and higher than o1-preview (1258). This Elo score puts the model at approximately the 86th percentile of programmers who compete on the Codeforces platform. o1-mini also performs well on the HumanEval coding benchmark and high-school level cybersecurity capture the flag challenges (CTFs). Codeforces 1650 1258 900 o1-mini o1-preview GPT-4o 0 200 400 600 800 1,000 1,200 1,400 1,600 1,800 Elo HumanEval 92.4% 92.4% 90.2% o1-mini o1-preview GPT-4o 0 10 20 30 40 50 60 70 80 90 100 Accuracy Cybersecurity CTFs 28.7% 43.0% 20.0% o1-mini o1-preview GPT-4o 0 5 10 15 20 25 30 35 40 45 Accuracy (Pass@12) STEM: On some academic benchmarks requiring reasoning, such as GPQA (science) and MATH-500, o1-mini outperforms GPT-4o. o1-mini does not perform as well as GPT-4o on tasks such as MMLU and lags behind o1-preview on GPQA due to its lack of broad world knowledge. MMLU 0-shot CoT 88.7% 85.2% 90.8% 92.3% GPT-4o o1-mini o1-preview o1 0 10 20 30 40 50 60 70 80 90 100 GPQA Diamond, 0-shot CoT 53.6% 60.0% 73.3% 77.3% GPT-4o o1-mini o1-preview o1 0 10 20 30 40 50 60 70 80 90 100 MATH-500 0-shot CoT 60.3% 90.0% 85.5% 94.8% GPT-4o o1-mini o1-preview o1 0 10 20 30 40 50 60 70 80 90 100 Human preference evaluation: We had human raters compare o1-mini to GPT-4o on challenging, open-ended prompts in various domains, using the same methodology as our o1-preview vs GPT-4o comparison. Similar to o1-preview, o1-mini is preferred to GPT-4o in reasoning-heavy domains, but is not preferred to GPT-4o in language-focused domains. Human preference evaluation vs chatgpt-4o-latest o1-preview o1-mini Personal Writing Editing Text Computer Programming Data Analysis Mathematical Calculation 0 20 40 60 80 100 Win Rate vs GPT-4o (%) Domain Model Speed As a concrete example, we compared responses from GPT-4o, o1-mini, and o1-preview on a word reasoning question. While GPT-4o did not answer correctly, both o1-mini and o1-preview did, and o1-mini reached the answer around 3-5x faster. Chat speed comparison Safety o1-mini is trained using the same alignment and safety techniques as o1-preview. The model has 59% higher jailbreak robustness on an internal version of the StrongREJECT dataset compared to GPT-4o. Before deployment, we carefully assessed the safety risks of o1-mini using the same approach to preparedness, external red-teaming, and safety evaluations as o1-preview. We are publishing the detailed results from these evaluations in the accompanying system card. Metric GPT-4o o1-mini % Safe completions refusal on harmful prompts (standard) 0.99 0.99 % Safe completions on harmful prompts (Challenging: jailbreaks & edge cases) 0.714 0.932 % Compliance on benign edge cases (“not over-refusal”) 0.91 0.923 [email protected] StrongREJECT jailbreak eval (Souly et al. 2024(opens in a new window)) 0.22 0.83 Human sourced jailbreak eval 0.77 0.95 Limitations and What’s Next Due to its specialization on STEM reasoning capabilities, o1-mini’s factual knowledge on non-STEM topics such as dates, biographies, and trivia is comparable to small LLMs such as GPT-4o mini. We will improve these limitations in future versions, as well as experiment with extending the model to other modalities and specialities outside of STEM. https://openai.com/index/openai-o1-mini-advancing-cost-efficient-reasoning/

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> [user request] <TEXT> [context document]

explain, in plain language, why looser access to methadone medications is more important than ever because of the current fetnanyl epidemic in the united states

Over the past several years, the increasing prevalence of fentanyl in the drug supply has created an unprecedented overdose death rate and other devastating consequences. People with an opioid use disorder (OUD) urgently need treatment not just to protect them from overdosing but also to help them achieve recovery, but highly effective medications like buprenorphine and methadone remain underused. Amid this crisis, it is critical that methadone, in particular, be made more accessible, as it may hold unique clinical advantages in the age of fentanyl. Growing evidence suggests that methadone is as safe and effective as buprenorphine for patients who use fentanyl. In a 2020 naturalistic follow-up study, 53% of patients admitted to methadone treatment who tested positive for fentanyl at intake were still in treatment a year later, compared to 47% for patients who tested negative. Almost all (99%) of those retained in treatment achieved remission. An earlier study similarly found that 89% of patients who tested positive for fentanyl at methadone treatment intake and who remained in treatment at 6 months achieved abstinence. Methadone may even be preferable for patients considered to be at high risk for leaving OUD treatment and overdosing on fentanyl. Comparative effectiveness evidence is emerging which shows that people with OUD in British Columbia given buprenorphine/naloxone when initiating treatment were 60% more likely to discontinue treatment than those who received methadone (1). More research is needed on optimal methadone dosing in patients with high opioid tolerance due to use of fentanyl, as well as on induction protocols for these patients. It is possible that escalation to a therapeutic dose may need to be more rapid. It remains the case that only a fraction of people who could benefit from medication treatment for OUD (MOUD) receive it, due to a combination of structural and attitudinal barriers. A study using data from the National Survey on Drug Use and Health (NSDUH) from 2019—that is, pre-pandemic—found that only slightly more than a quarter (27.8%) of people who needed OUD treatment in the past year had received medication to treat their disorder. But a year into the pandemic, in 2021, the proportion had dropped to just 1 in 5. Efforts have been made to expand access to MOUD. For instance, in 2021, the U.S. Department of Health and Human Services (HHS) advanced the most comprehensive Overdose Prevention Strategy to date. Under this strategy, in 2023, HHS eliminated the X-waiver requirement for buprenorphine. But in the fentanyl era, expanded access to methadone too is essential, although there are even greater attitudinal and structural barriers to overcome with this medication. People in methadone treatment, who must regularly visit an opioid treatment program (OTP), face stigma from their community and from providers. People in rural areas may have difficulty accessing or sticking with methadone treatment if they live far from an OTP. SAMHSA’s changes to 42 CFR Part 8 (“Medications for the Treatment of Opioid Use Disorder”) on January 30, 2024 were another positive step taken under the HHS Overdose Prevention Strategy. The new rule makes permanent the increased take-home doses of methadone established in March 2020 during the COVID pandemic, along with other provisions aimed to broaden access like the ability to initiate methadone treatment via telehealth. Studies show that telehealth is associated with increased likelihood of receiving MOUD and that take-home doses increase treatment retention. Those changes that were implemented during the COVID pandemic have not been associated with adverse outcomes. An analysis of CDC overdose death data from January 2019 to August 2021 found that the percentage of overdose deaths involving methadone relative to all drug overdose deaths declined from 4.5% to 3.2% in that period. Expanded methadone access also was not associated with significant changes in urine drug test results, emergency department visits, or increases in overdose deaths involving methadone. An analysis of reports to poison control centers found a small increase in intentional methadone exposures in the year following the loosening of federal methadone regulations, but no significant increases in exposure severity, hospitalizations, or deaths. Patients themselves reported significant benefits from increased take-home methadone and other COVID-19 protocols. Patients at one California OTP in a small qualitative study reported increased autonomy and treatment engagement. Patients at three rural OTPs in Oregon reported increased self-efficacy, strengthened recovery, and reduced interpersonal conflict. The U.S. still restricts methadone prescribing and dispensing more than most other countries, but worries over methadone’s safety and concerns about diversion have made some physicians and policymakers hesitant about policy changes that would further lower the guardrails around this medication. Methadone treatment, whether for OUD or pain, is not without risks. Some studies have found elevated rates of overdose during the induction and stabilization phase of maintenance treatment, potentially due to starting at too high a dose, escalating too rapidly, or drug interactions. Although greatly increased prescribing of methadone to treat pain two decades ago was associated with diversion and a rise in methadone overdoses, overdoses declined after 2006, along with methadone’s use as an analgesic, even as its use for OUD increased. Most methadone overdoses are associated with diversion and, less often, prescription for chronic pain; currently, 70 percent of methadone overdoses involve other opioids (like fentanyl) or benzodiazepines. Recent trials of models of methadone dispensing in pharmacies and models of care based in other settings than OTPs have not supported concerns that making methadone more widely available will lead to harms like overdose. In two feasibility studies, stably maintained patients from OTPs in Baltimore, Maryland and Raleigh, North Carolina who received their methadone from a local pharmacy found this model to be highly satisfactory, with no positive urine screens, adverse events, or safety issues. An older pilot study in New Mexico found that prescribing methadone in a doctor’s office and dispensing in a community pharmacy, as well as methadone treatment delivered by social workers, produced better outcomes than standard care in an OTP for a sample of stably maintained female methadone patients. Critics of expanded access to methadone outside OTPs sometimes argue that the medication should not be offered without accompanying behavioral treatment. Data suggest that counseling is not essential. In wait-list studies, methadone treatment was effective at reducing opioid use on its own, and patients stayed in treatment. However, counseling may have benefits or even be indispensable for some patients to help them improve their psychosocial functioning and reduce other drug use. How to personalize the intensity and the level of support needed is a question that requires further investigation. Over the past two decades, the opioid crisis has accelerated the integration of addiction care in the U.S. with mainstream medicine. Yet methadone, the oldest and still one of the most effective medications in our OUD treatment toolkit, remains siloed. In the current era of powerful synthetic opioids like fentanyl dominating the statistics on drug addiction and overdose, it is time to make this effective medication more accessible to all who could benefit. The recent rules making permanent the COVID-19 provisions are an essential step in the right direction, but it will be critical to pursue other ways that methadone can safely be made more available to a wider range of patients with OUD. Although more research would be of value, the initial evidence suggests that providing methadone outside of OTPs is feasible, acceptable, and leads to good outcomes.

<TASK DESCRIPTION> Only use the provided text to answer the question, no outside sources. <QUESTION> explain, in plain language, why looser access to methadone medications is more important than ever because of the current fetnanyl epidemic in the united states <TEXT> Over the past several years, the increasing prevalence of fentanyl in the drug supply has created an unprecedented overdose death rate and other devastating consequences. People with an opioid use disorder (OUD) urgently need treatment not just to protect them from overdosing but also to help them achieve recovery, but highly effective medications like buprenorphine and methadone remain underused. Amid this crisis, it is critical that methadone, in particular, be made more accessible, as it may hold unique clinical advantages in the age of fentanyl. Growing evidence suggests that methadone is as safe and effective as buprenorphine for patients who use fentanyl. In a 2020 naturalistic follow-up study, 53% of patients admitted to methadone treatment who tested positive for fentanyl at intake were still in treatment a year later, compared to 47% for patients who tested negative. Almost all (99%) of those retained in treatment achieved remission. An earlier study similarly found that 89% of patients who tested positive for fentanyl at methadone treatment intake and who remained in treatment at 6 months achieved abstinence. Methadone may even be preferable for patients considered to be at high risk for leaving OUD treatment and overdosing on fentanyl. Comparative effectiveness evidence is emerging which shows that people with OUD in British Columbia given buprenorphine/naloxone when initiating treatment were 60% more likely to discontinue treatment than those who received methadone (1). More research is needed on optimal methadone dosing in patients with high opioid tolerance due to use of fentanyl, as well as on induction protocols for these patients. It is possible that escalation to a therapeutic dose may need to be more rapid. It remains the case that only a fraction of people who could benefit from medication treatment for OUD (MOUD) receive it, due to a combination of structural and attitudinal barriers. A study using data from the National Survey on Drug Use and Health (NSDUH) from 2019—that is, pre-pandemic—found that only slightly more than a quarter (27.8%) of people who needed OUD treatment in the past year had received medication to treat their disorder. But a year into the pandemic, in 2021, the proportion had dropped to just 1 in 5. Efforts have been made to expand access to MOUD. For instance, in 2021, the U.S. Department of Health and Human Services (HHS) advanced the most comprehensive Overdose Prevention Strategy to date. Under this strategy, in 2023, HHS eliminated the X-waiver requirement for buprenorphine. But in the fentanyl era, expanded access to methadone too is essential, although there are even greater attitudinal and structural barriers to overcome with this medication. People in methadone treatment, who must regularly visit an opioid treatment program (OTP), face stigma from their community and from providers. People in rural areas may have difficulty accessing or sticking with methadone treatment if they live far from an OTP. SAMHSA’s changes to 42 CFR Part 8 (“Medications for the Treatment of Opioid Use Disorder”) on January 30, 2024 were another positive step taken under the HHS Overdose Prevention Strategy. The new rule makes permanent the increased take-home doses of methadone established in March 2020 during the COVID pandemic, along with other provisions aimed to broaden access like the ability to initiate methadone treatment via telehealth. Studies show that telehealth is associated with increased likelihood of receiving MOUD and that take-home doses increase treatment retention. Those changes that were implemented during the COVID pandemic have not been associated with adverse outcomes. An analysis of CDC overdose death data from January 2019 to August 2021 found that the percentage of overdose deaths involving methadone relative to all drug overdose deaths declined from 4.5% to 3.2% in that period. Expanded methadone access also was not associated with significant changes in urine drug test results, emergency department visits, or increases in overdose deaths involving methadone. An analysis of reports to poison control centers found a small increase in intentional methadone exposures in the year following the loosening of federal methadone regulations, but no significant increases in exposure severity, hospitalizations, or deaths. Patients themselves reported significant benefits from increased take-home methadone and other COVID-19 protocols. Patients at one California OTP in a small qualitative study reported increased autonomy and treatment engagement. Patients at three rural OTPs in Oregon reported increased self-efficacy, strengthened recovery, and reduced interpersonal conflict. The U.S. still restricts methadone prescribing and dispensing more than most other countries, but worries over methadone’s safety and concerns about diversion have made some physicians and policymakers hesitant about policy changes that would further lower the guardrails around this medication. Methadone treatment, whether for OUD or pain, is not without risks. Some studies have found elevated rates of overdose during the induction and stabilization phase of maintenance treatment, potentially due to starting at too high a dose, escalating too rapidly, or drug interactions. Although greatly increased prescribing of methadone to treat pain two decades ago was associated with diversion and a rise in methadone overdoses, overdoses declined after 2006, along with methadone’s use as an analgesic, even as its use for OUD increased. Most methadone overdoses are associated with diversion and, less often, prescription for chronic pain; currently, 70 percent of methadone overdoses involve other opioids (like fentanyl) or benzodiazepines. Recent trials of models of methadone dispensing in pharmacies and models of care based in other settings than OTPs have not supported concerns that making methadone more widely available will lead to harms like overdose. In two feasibility studies, stably maintained patients from OTPs in Baltimore, Maryland and Raleigh, North Carolina who received their methadone from a local pharmacy found this model to be highly satisfactory, with no positive urine screens, adverse events, or safety issues. An older pilot study in New Mexico found that prescribing methadone in a doctor’s office and dispensing in a community pharmacy, as well as methadone treatment delivered by social workers, produced better outcomes than standard care in an OTP for a sample of stably maintained female methadone patients. Critics of expanded access to methadone outside OTPs sometimes argue that the medication should not be offered without accompanying behavioral treatment. Data suggest that counseling is not essential. In wait-list studies, methadone treatment was effective at reducing opioid use on its own, and patients stayed in treatment. However, counseling may have benefits or even be indispensable for some patients to help them improve their psychosocial functioning and reduce other drug use. How to personalize the intensity and the level of support needed is a question that requires further investigation. Over the past two decades, the opioid crisis has accelerated the integration of addiction care in the U.S. with mainstream medicine. Yet methadone, the oldest and still one of the most effective medications in our OUD treatment toolkit, remains siloed. In the current era of powerful synthetic opioids like fentanyl dominating the statistics on drug addiction and overdose, it is time to make this effective medication more accessible to all who could benefit. The recent rules making permanent the COVID-19 provisions are an essential step in the right direction, but it will be critical to pursue other ways that methadone can safely be made more available to a wider range of patients with OUD. Although more research would be of value, the initial evidence suggests that providing methadone outside of OTPs is feasible, acceptable, and leads to good outcomes. https://nida.nih.gov/about-nida/noras-blog/2024/07/to-address-the-fentanyl-crisis-greater-access-to-methadone-is-needed

Please limit your knowledge to the document. Avoid generalizations and ensure accuracy by directly referencing the document's arguments and examples.

What are the main ideas presented in this study and what are the benefits ad consequences?

The biggest mistakes Canadians make on their taxes — and how to fix them Fizkes / Shutterstock By Tamar Satov We adhere to strict standards of editorial integrity to help you make decisions with confidence. Please be aware this post may contain links to products from our partners. We may receive a commission for products or services you sign up for through partner links. Maximize your tax savings by avoiding these common errors on Canadian income tax returns. Already goofed and want to know how to fix a mistake on your tax return? Here’s how to change your return after you’ve filed. Filing income taxes is a complicated process, so it’s not surprising that taxpayers often get things wrong on their returns. Sometimes, your mistake could have you paying more in taxes than you should. In other situations, you may have to give back the benefits you already received or face penalties or other fees. To help you get your return right the first time, we’ve come up with a list of the most common mistakes Canadians make on their taxes. But, if you already made one of these errors and want to know, “How do I fix a mistake on my tax return?” — don’t worry. We also explain how to correct your tax return after you’ve filed. Mistake #1: Forgetting allowable deductions or credits It’s hard to know which income tax deductions and credits you qualify for from year to year, especially since the government continually tinkers with the rules for existing tax breaks, adding new ones and eliminating others. If you don’t claim all the deductions and credits you are entitled to, you’ll pay more taxes than necessary — which you obviously want to avoid. Some of the more frequently overlooked credits and deductions include: o A non-refundable tax credit for the interest you paid on student loans; o A tax deduction for union or professional dues; o The $5,000 non-refundable home buyer’s tax credit, for those who bought a qualifying home in the past year and have not lived in a home they (or their spouse) owned in the past four years; o A tax deduction for work-related expenses that you paid for out of pocket — even if you are salaried. This year, the CRA has made it even easier to qualify for this deduction if you worked from home during the COVID-19 pandemic. One of the benefits of using tax software to file your taxes is that the better ones, such as TurboTax, will ask you a series of questions to determine which of the more than 400 deductions and credits you may be eligible for. That means you won’t leave tax savings on the table. READ MORE: The best tax return software in Canada Mistake #2: Claiming ineligible expenses On the flip side of missing tax breaks is claiming deductions or credits that don’t exist. According to the CRA, one of the classic examples here is related to moving expenses. Taxpayers who move at least 40 km closer to a new place of work or to study full-time at a post-secondary program can deduct a variety of moving costs, including transportation and storage, travel expenses, utility hookups and disconnections, and fees for cancelling a lease. But some taxpayers push the envelope by writing off ineligible expenses such as home staging, household repairs, and the cost of having their mail forwarded to the new address. Similarly, some students try to claim the student loan tax credit on interest fees they paid on personal loans, student lines of credit, or foreign student loans — even though these forms of borrowing are not eligible for the credit. Mistake #3: Getting rid of slips and receipts With the rise of online tax filing, which does not require taxpayers to send in all their slips and receipts along with their returns, some people fail to keep that paperwork handy. This is a problem since the CRA can (and often does) request to see receipts for things like childcare expenses, charitable donations, tuition fees, or any other expense related to a claim you’ve made. (Such requests are separate from an audit, which is much less likely, but could also happen.) Individuals are required to keep seven years’ worth of records on hand, and the CRA will only accept receipts (not invoices) that include the date of payment. If you cannot provide these documents when asked, your claims will be denied. Mistake #4: Misreporting your marital status You may not think of your squeeze as your spouse, but if you have been living together for at least 12 months, or you reside together and share a child (by birth or adoption), the CRA considers you to be in a common-law relationship, which must be declared on your tax return. It’s important that you correctly indicate your marital status, because some benefits that you may be eligible to receive, such as the GST/HST tax credit or the Canada Child Benefit, are based on spouses’ combined incomes. If you file as single, it could delay your payments, or you may even have to pay back some of the money you receive. On the plus side, spouses can pool or transfer some of their tax credits, which can lead to greater tax savings. This is another benefit of using tax software, as it will automatically optimize claims for medical expenses, charitable donations, pension splitting, and other credits when spouses prepare their returns at the same time. Mistake #5: Neglecting to transfer unused tax credits to other family Mmembers As mentioned above, individuals can transfer some of their tax credits to a spouse if they don’t have enough income or taxes owing to make full use of them. In some cases, such as the $5,000 tuition tax credit, unused amounts can also be transferred to a parent or grandparent. So, for example, if you are a full-time student at an eligible education institution, you can claim a non-refundable tax credit equal to 15% of the tuition you paid (up to $5,000). Because it is a non-refundable tax credit — which can only reduce the amount of tax you owe, it can’t pay out any extra benefit — you can only use the portion of the credit that reduces your taxes to zero. At that point, any remaining amount may be transferred to a spouse, parent or grandparent, which can lead to greater tax savings (especially if they are in a higher tax bracket than you are). Mistake #6: Missing the tax deadline Because of COVID-19, the 2019 tax filing deadline was extended dramatically in 2020. But deadlines returned to normal in 2021, and 2022 appears to be the same. You’ll need to file your 2021 taxes by May 2, 2022, for employed Canadians and by June 15, 2022, if you are self-employed. o You won’t get your refund on time. If you’re owed a refund, as is the case for more than 60% of tax filers, it will be delayed — and the government won’t pay you any interest even though it kept your money longer than necessary. o It could delay benefit payments. The government can’t assess your eligibility for payments such as the GST/HST Credit or Canada Child Benefit until you file your tax return. o You may face interest charges and penalty fees. If you have taxes owing and don’t file by the deadline, the CRA will charge you compound daily interest on your unpaid balance starting the very next day. Furthermore, you will be subject to a 5% late-filing penalty, and an extra 1% for every month after that (up to 12 months). These fees can really snowball over time, as the penalties rise to 10% (and 2% extra for every month) if you’ve already been late with your taxes in the past three years. Plus, the CRA will even charge you interest on your penalties Mistake #7: Not realizing some benefits are taxable If you received COVID-19 emergency relief from the government (like the Canada Emergency Response Benefit or CERB), that benefit most likely helped keep your finances afloat during some very financially turbulent times. But the money you received under this program and others like it wasn’t without strings attached. You’ll need to declare any benefits you received on your upcoming income tax return. On top of that, these benefits are taxable, which means they do not have income tax deducted at the source. So if you claimed CERB or other COVID benefits during 2020, you would have to pay a portion of it back at tax time as income tax. It’s smart to do your calculations early using a simple income tax calculator to help you determine how much you might owe, so you aren’t shocked at tax time. Mistake #8: Ignoring mistakes you made on previous returns So, now that you know about the most common mistakes Canadians make on their taxes, you can avoid them when you prepare this year’s return. But what if upon reviewing this list you realize you made some of these mistakes in the past? Or perhaps you found a misplaced T-slip, or it arrived late. Like many Canadians, you may be wondering, “Can I correct my tax return?” Thankfully, you don’t have to accept that you missed out on tax savings, or sit around in fear that the CRA may come after you for additional payments. Instead, you can (and should) correct your tax return, as we explain below. 

Please limit your knowledge to the document. Avoid generalizations and ensure accuracy by directly referencing the document's arguments and examples. What are the main ideas presented in this study and what are the benefits ad consequences? The biggest mistakes Canadians make on their taxes — and how to fix them Fizkes / Shutterstock By Tamar Satov We adhere to strict standards of editorial integrity to help you make decisions with confidence. Please be aware this post may contain links to products from our partners. We may receive a commission for products or services you sign up for through partner links. Maximize your tax savings by avoiding these common errors on Canadian income tax returns. Already goofed and want to know how to fix a mistake on your tax return? Here’s how to change your return after you’ve filed. Filing income taxes is a complicated process, so it’s not surprising that taxpayers often get things wrong on their returns. Sometimes, your mistake could have you paying more in taxes than you should. In other situations, you may have to give back the benefits you already received or face penalties or other fees. To help you get your return right the first time, we’ve come up with a list of the most common mistakes Canadians make on their taxes. But, if you already made one of these errors and want to know, “How do I fix a mistake on my tax return?” — don’t worry. We also explain how to correct your tax return after you’ve filed. Mistake #1: Forgetting allowable deductions or credits It’s hard to know which income tax deductions and credits you qualify for from year to year, especially since the government continually tinkers with the rules for existing tax breaks, adding new ones and eliminating others. If you don’t claim all the deductions and credits you are entitled to, you’ll pay more taxes than necessary — which you obviously want to avoid. Some of the more frequently overlooked credits and deductions include: o A non-refundable tax credit for the interest you paid on student loans; o A tax deduction for union or professional dues; o The $5,000 non-refundable home buyer’s tax credit, for those who bought a qualifying home in the past year and have not lived in a home they (or their spouse) owned in the past four years; o A tax deduction for work-related expenses that you paid for out of pocket — even if you are salaried. This year, the CRA has made it even easier to qualify for this deduction if you worked from home during the COVID-19 pandemic. One of the benefits of using tax software to file your taxes is that the better ones, such as TurboTax, will ask you a series of questions to determine which of the more than 400 deductions and credits you may be eligible for. That means you won’t leave tax savings on the table. READ MORE: The best tax return software in Canada Mistake #2: Claiming ineligible expenses On the flip side of missing tax breaks is claiming deductions or credits that don’t exist. According to the CRA, one of the classic examples here is related to moving expenses. Taxpayers who move at least 40 km closer to a new place of work or to study full-time at a post-secondary program can deduct a variety of moving costs, including transportation and storage, travel expenses, utility hookups and disconnections, and fees for cancelling a lease. But some taxpayers push the envelope by writing off ineligible expenses such as home staging, household repairs, and the cost of having their mail forwarded to the new address. Similarly, some students try to claim the student loan tax credit on interest fees they paid on personal loans, student lines of credit, or foreign student loans — even though these forms of borrowing are not eligible for the credit. Mistake #3: Getting rid of slips and receipts With the rise of online tax filing, which does not require taxpayers to send in all their slips and receipts along with their returns, some people fail to keep that paperwork handy. This is a problem since the CRA can (and often does) request to see receipts for things like childcare expenses, charitable donations, tuition fees, or any other expense related to a claim you’ve made. (Such requests are separate from an audit, which is much less likely, but could also happen.) Individuals are required to keep seven years’ worth of records on hand, and the CRA will only accept receipts (not invoices) that include the date of payment. If you cannot provide these documents when asked, your claims will be denied. Mistake #4: Misreporting your marital status You may not think of your squeeze as your spouse, but if you have been living together for at least 12 months, or you reside together and share a child (by birth or adoption), the CRA considers you to be in a common-law relationship, which must be declared on your tax return. It’s important that you correctly indicate your marital status, because some benefits that you may be eligible to receive, such as the GST/HST tax credit or the Canada Child Benefit, are based on spouses’ combined incomes. If you file as single, it could delay your payments, or you may even have to pay back some of the money you receive. On the plus side, spouses can pool or transfer some of their tax credits, which can lead to greater tax savings. This is another benefit of using tax software, as it will automatically optimize claims for medical expenses, charitable donations, pension splitting, and other credits when spouses prepare their returns at the same time. Mistake #5: Neglecting to transfer unused tax credits to other family Mmembers As mentioned above, individuals can transfer some of their tax credits to a spouse if they don’t have enough income or taxes owing to make full use of them. In some cases, such as the $5,000 tuition tax credit, unused amounts can also be transferred to a parent or grandparent. So, for example, if you are a full-time student at an eligible education institution, you can claim a non-refundable tax credit equal to 15% of the tuition you paid (up to $5,000). Because it is a non-refundable tax credit — which can only reduce the amount of tax you owe, it can’t pay out any extra benefit — you can only use the portion of the credit that reduces your taxes to zero. At that point, any remaining amount may be transferred to a spouse, parent or grandparent, which can lead to greater tax savings (especially if they are in a higher tax bracket than you are). Mistake #6: Missing the tax deadline Because of COVID-19, the 2019 tax filing deadline was extended dramatically in 2020. But deadlines returned to normal in 2021, and 2022 appears to be the same. You’ll need to file your 2021 taxes by May 2, 2022, for employed Canadians and by June 15, 2022, if you are self-employed. o You won’t get your refund on time. If you’re owed a refund, as is the case for more than 60% of tax filers, it will be delayed — and the government won’t pay you any interest even though it kept your money longer than necessary. o It could delay benefit payments. The government can’t assess your eligibility for payments such as the GST/HST Credit or Canada Child Benefit until you file your tax return. o You may face interest charges and penalty fees. If you have taxes owing and don’t file by the deadline, the CRA will charge you compound daily interest on your unpaid balance starting the very next day. Furthermore, you will be subject to a 5% late-filing penalty, and an extra 1% for every month after that (up to 12 months). These fees can really snowball over time, as the penalties rise to 10% (and 2% extra for every month) if you’ve already been late with your taxes in the past three years. Plus, the CRA will even charge you interest on your penalties Mistake #7: Not realizing some benefits are taxable If you received COVID-19 emergency relief from the government (like the Canada Emergency Response Benefit or CERB), that benefit most likely helped keep your finances afloat during some very financially turbulent times. But the money you received under this program and others like it wasn’t without strings attached. You’ll need to declare any benefits you received on your upcoming income tax return. On top of that, these benefits are taxable, which means they do not have income tax deducted at the source. So if you claimed CERB or other COVID benefits during 2020, you would have to pay a portion of it back at tax time as income tax. It’s smart to do your calculations early using a simple income tax calculator to help you determine how much you might owe, so you aren’t shocked at tax time. Mistake #8: Ignoring mistakes you made on previous returns So, now that you know about the most common mistakes Canadians make on their taxes, you can avoid them when you prepare this year’s return. But what if upon reviewing this list you realize you made some of these mistakes in the past? Or perhaps you found a misplaced T-slip, or it arrived late. Like many Canadians, you may be wondering, “Can I correct my tax return?” Thankfully, you don’t have to accept that you missed out on tax savings, or sit around in fear that the CRA may come after you for additional payments. Instead, you can (and should) correct your tax return, as we explain below. 

You can only respond to the prompt using information in the context block.

Discuss the concept of military necessity as outlined in this article and its relationship to contemporary asymmetric conflict.

Abstract Inequality in arms, indeed, significant disparity between belligerents, has become a prominent feature of various contemporary armed conflicts. Such asymmetries, albeit not at all a new phenomenon in the field of warfare, no longer constitute a random occurrence of singular battles. As a structural characteristic of modern-day warfare asymmetric conflict structures have repercussions on the application of fundamental principles of international humanitarian law. How, for example, can the concept of military necessity, commonly understood to justify the degree of force necessary to secure military defeat of the enemy, be reconciled with a constellation in which one side in the conflict is from the outset bereft of any chance of winning the conflict militarily? Moreover, military imbalances of this scope evidently carry incentives for the inferior party to level out its inferiority by circumventing accepted rules of warfare. This article attempts tentatively to assess the repercussions this could have on the principle of reciprocity, especially the risk of the instigation of a destabilizing dynamic of negative reciprocity which ultimately could lead to a gradual intensification of a mutual disregard of international humanitarian law. Introduction With only one remaining superpower and more generally the considerable and predictably widening technological divide, an imbalance in the military capacity of warring parties has become a characteristic feature of contemporary armed conflicts. Coupled with a growing involvement of non-state entities, the disparity between belligerents is steadily increasing, and various contemporary armed conflicts appear to be more and more asymmetric in structure. Unlike the geostrategic set-up that prevailed throughout the cold war period, it is a widely perceived paradox of today’s strategic environment that military superiority may actually accentuate the threat of nuclear, biological, chemical and, generally speaking, perfidious attack. Indeed, direct attacks against civilians, hostage-taking and the use of human shields – practices that have long been outlawed in armed conflicts– have seen a revival in recent conflicts in which the far weaker party has often sought to gain a comparative advantage over the militarily superior enemy by resorting to such practices as a matter of strategy. International terrorism, although not necessarily conducted within the context of an armed conflict triggering the application of international humanitarian law (IHL), is often regarded as the epitome of such asymmetry. At the same time militarily superior parties at the other end of the spectrum have had recourse to indiscriminate attacks, illegal interrogation practices and renditions, as well as legally dubious practices such as targeted killings or hardly reviewable covert operations, in order to strike at their frequently amorphous enemy. Significant inequality of arms, that is a disparate distribution of military strength and technological capability in a given conflict, seemingly creates incentives for adversaries to resort to means and methods of warfare that undermine and are sometimes an outright violation of long-accepted standards of international humanitarian law. The war between the US-led Coalition and Iraq or the war in Afghanistan are clear examples. This tendency is reinforced if belligerents differ in nature, as in the recent conflict between Israel and Hezbollah (‘‘party of God’’)– the Lebanon-based Shia Islamic militia and political organization– or if factual asymmetries are combined with a legal asymmetry, that is in a constellation in which one side is accorded little or no legal standing. To be sure, perfect symmetries have rarely been present in war. However, the patterns of non-compliance displayed in various contemporary conflicts seem to be more structured and systematic than ever before. The present study first seeks to verify this assumption. It considers whether factual and potentially legal asymmetries do indeed constitute an incentive for breaches of international humanitarian law provisions, and, if so, how patterns of contemporary conflicts differ from those of previous conflicts that likewise exhibited discernible asymmetries. In a second step, closer scrutiny is given to the actual patterns of non-compliance in asymmetric scenarios, particularly in the light of the interplay of the principle of distinction and the principle of proportionality. Neither the term ‘‘asymmetric warfare’’ nor the sometimes synonymously employed terms ‘‘fourth-generation warfare’’ or ‘‘non-linear war’’ have thus far been concordantly defined.3 It is not the intention of this study to venture into this perhaps impenetrable terrain. Analysis shows, however, that there is a noticeable tendency in contemporary conflicts towards an increasing inequality between belligerents in terms of weaponry. While this is a long-known phenomenon in non-international armed conflicts, evaluation of the effects of military disparity in international armed conflicts continues, as does the debate over the extent to which transnational conflicts involving states and non-state entities should be subject to the laws of war. In attempting to approach this debate from a somewhat different angle, it is the overall purpose of this study to gauge the long-term repercussions that asymmetric conflict structures may have on the fundamental principles of international humanitarian law and thereby tentatively to assess the degree of asymmetry– that is, the level of military disparity between belligerents– that can still be reconciled with the legal regime applicable in times of war.5 To this end the study, in a third step, weighs the traditional concept of military necessity as laid down in the Lieber Code of 1863 against the promulgated necessities in asymmetric conflicts of our time. Even though the fundamental concepts and principles of the laws of war have been designed as prophylactic mechanisms flexible enough to outlast changes in the way in which wars are waged, it is here contended that the concept of military necessity and the principle of distinction presuppose a minimum degree of symmetry and therefore cannot be applied in subordinative constellations akin to human rights patterns, as are commonly seen in the fight against international terrorism. The vantage point for the fourth and final part of the analysis is the principle of reciprocity. As the military mismatch between conflicting parties in numerous modern armed conflicts becomes more marked, the balancing influence of the reciprocity entailed by the traditional concept of symmetric warfare is gradually being undermined.6 While the deterrent effects of an increasingly effective system of international criminal law and of media coverage and public opinion– although the last two are ambivalent factors that could also be used for the opposite purpose– could arguably help to contain non-compliant behaviour in war, international humanitarian law might thus be simultaneously bereft of its own inherent regulating mechanisms which have traditionally taken effect in the combat zone itself. The destabilizing dynamic of reciprocity could lead to a gradual and perhaps insidious erosion of the protective scope of core principles of international humanitarian law. Repeated violations of, for example, the principle of distinction by one party to a conflict are likely to induce the other side to expand its perception of what is militarily necessary, and hence proportional, when engaging in battle against such an enemy. In the final stage, and admittedly only as a worst-case scenario, an intentional and deceitful deviation from accepted standards regulating the conduct of hostilities carries the considerable risk of starting a vicious circle of ever greater negative reciprocity, in which the expectations of the warring parties are transformed into an escalating mutual noncompliance with international humanitarian law. A heightened risk of structural non-compliance? Historically, the majority of laws on international armed conflict have been designed on the basis of Clausewitz’s arguably rather Eurocentric conception of war, that is, the assumption of symmetric conflicts taking place between state armies of roughly equal military strength or at least comparable organizational structures. Throughout most of the nineteenth and twentieth centuries the dominant powers engaged in sustained arms races either to maintain a peace ensuring symmetry or to establish a tactical asymmetry vis-a `-vis their opponents as a guarantee of military victory in war.7 But quite apart from the biblical story of David and Goliath it is evident that asymmetry in the sense of military disparity is no new phenomenon.8 Nor is it a concept entirely alien to IHL. With the intrinsic disparity of the parties concerned, and even though the threshold criteria of Article 1 of Additional Protocol II to the 1949 Geneva Conventions arguably help to ensure a minimum degree of comparability between those parties, non-international armed conflicts are inherently asymmetric. It was moreover already accepted in the classic concept of symmetric warfare that the structure of conflicts could shift from symmetric to asymmetric, for by the time a conflict drew to its close and one party had gained the upper hand, the initial military balance would be out of kilter. More recently, during the Diplomatic Conference that led to the adoption of Additional Protocol I, states taking part not only acknowledged the persistence of significant disparities in military capacity but accepted that factual disparity between opponents may even lead to differing humanitarian law obligations. For example, with respect to Article 57 of Additional Protocol I on the obligation to take precautions in attack,9 the Indian delegation pointed out that according to the chosen wording the content of the due diligence obligation enshrined therein– that is, the precise identification of objectives as military or civilian– largely depended on the technical means of detection available to the belligerents.10 Despite these concerns, the present wording was accepted on the implicit understanding that because of prevailing factual disparities, international humanitarian law obligations may impose differing burdens in practice.11 Schwarzenberger has pointed out that the protective scope of the laws of war has historically been the strongest in duel-type wars between comparable belligerents that were fought for limited purposes, such as the Crimean War of 1853–6 or the Franco-German War of 1870–1, whereas in major wars such as the Napoleonic wars or the two world wars of the twentieth century– wars that were fought to the bitter end– the weaker side often tended to seek short-term advantages by violating the laws of war.12 Indeed, violations of the laws of war have occurred in nearly every case in which IHL has been applicable,13 and the risk that one party may order or connive in large-scale violations of the laws of war in order to gain a tempting advantage or stave off in some way an otherwise threatening defeat has always hovered over the legal regime intended to regulate conduct in armed conflicts.14 However, in symmetric constellations such instances have tended to remain marginal, often limited to the final stages of a war and confined to individual battles in which defeat seemed inevitable, or resort to perfidy or similarly prohibited tactics was perceived as guaranteeing an immediate tactical breakthrough in what was otherwise a military stalemate. As a result of the evident disparate military capabilities of opponents in certain contemporary conflicts, incentives for violations of IHL seem in comparison to have reached a new height. Non-compliance with the provisions of IHL is no longer a random event, confined to temporally and spatially limited incidents within a conflict, but has become a recurrent structural feature that characterizes many of today’s armed conflicts from the outset. The reason is that, faced with an enemy of overwhelming technological superiority, the weaker party ab initio has no chance of winning the war militarily. Figures from the recent war against Iraq illustrate this imbalance of power and capacity quite well. While the Iraqi air force reportedly never left the ground, Coalition forces flew rather more than 20,000 sorties, during which only one fixed-wing aircraft and only seven aircraft in all were lost to hostile fire.15 Evidence of a comparable inequality in the military capability of belligerents will probably become available in the aftermath of the recent conflict in Lebanon. Without anticipating the more detailed analysis below, it should be noted that the Iraqi army’s widespread infringements during the international conflict against the US-led Coalition, as well as Hezbollah’s indiscriminate attacks, stem to a significant extent from the blatant inequality in weaponry. Practices employed by the Iraqi army included recourse to human shields, abuse of the red cross and red crescent emblems, the use of anti-personnel mines and the placing of military objects in protected areas such as mosques and hospitals. Clearly, there is thus an elevated risk that the militarily inferior party, unable to identify any military weaknesses of its superior opponent, may feel compelled systematically to offset the enemy’s superiority by resorting to means and methods of warfare outside the realm of international humanitarian law. At the same time the use of ‘‘unthinkable’’ tactics as well as the tactical circumvention of accepted IHL standards creates a barrier that cannot be readily overcome by military superiority alone. Apart from the ongoing hostilities in Iraq, the tactics employed by the Somali tribal leader Farah Aydid in 1993 are a good example of this. In conventional terms, his forces were no match for heavily armed and technologically sophisticated airborne US troops. However, by using primitive weapons and communication systems– which reportedly varied from cellular phones to tribal drums– and by resorting to ‘‘unthinkable’’ tactics and to ‘‘barbaric’’ acts perpetrated for the benefit of the news media, the militia convinced the leadership of the United States that despite the military backwardness of the Somali forces the price of involvement in Somalia was very high. In the course of the war against Iraq the use of cluster munitions in populated areas, as well as the alleged use of white phosphorus and the continued recourse by US and British forces to ‘‘decapitation’’ strikes that caused high numbers of civilian casualties, partly constituted indiscriminate attacks and arguably a failure to take ‘‘all feasible precautions’’ as required by IHL. There are thus apparent incentives for both sides to give increasing priority, potentially to the detriment of humanitarian considerations, to the necessities of such a kind of warfare. Patterns of non-compliance: the interplay between the principle of distinction and the principle of proportionality Recent conflict patterns suggest that militarily inferior parties, in order to evade attack by an enemy of insurmountable superiority or to level out inequalities in military power, tend in particular to instrumentalize and intentionally manipulate the principle of distinction. This manipulation may occur in different ways.18 Similarly, superior parties are likely to lower the barrier of proportionality in response to a systematic misuse of the principle of distinction and their resulting inability to tackle the enemy effectively. The following description of potential strategies that belligerents may feel compelled to adopt when faced with overwhelming odds or systematic deviations from accepted legal rules is merely intended to facilitate understanding of likely patterns of non-compliance and does not claim to be comprehensive. It is part of the very nature of asymmetric strategies that they are impossible to predict. The principle of distinction As a defensive strategy when facing a technologically superior enemy it is essential, but ever more difficult, to stay out of reach and conceal one’s presence as a combatant. Hiding in mountainous areas, caves, underground facilities and tunnels is one way. However, another means of doing so quickly and efficiently is readily available by virtue of the provisions of IHL themselves. In view of the various forms of protection accorded to civilians, assuming civilian guise is an easy way to evade the enemy and, unlike the more traditional guerrilla-style tactics of hiding underground or in inaccessible areas, it cannot be countered by the development of advanced discovery technologies. Indeed, in order to keep Coalition forces from identifying them as enemies, that is as legitimate targets, many Iraqi soldiers in the recent war reportedly quite often discarded their uniforms. This is not a prohibited tactic, as long as such practices are not used to launch an attack under the cover of protected status; according to Article 4 of the Third Geneva Convention the absence of any fixed distinctive sign recognizable at a distance merely leads to the loss of combatant status and the corresponding privileges. Still, despite its legality such a practice will, if employed as a matter of strategy, create considerable uncertainty about a person’s status and thus subtly erode the effectiveness of the fundamental and, in the words of the International Court of Justice (ICJ), intransgressible principle of distinction. Evidently the notion of distinction, that is, the legally prescribed invulnerability of certain persons and objects, can if manipulated offer manifold loopholes for the evasion of attack.22 The dividing line between legal tactics and illegitimate practices is easily crossed. The misuse of protective emblems for the concealment of military objects is a case in point, and the marking of the Ba’ath Party building in Basra with the ICRC emblem is a flagrant example of such tactics.23 To protect military objects whose nature could not be so readily concealed, weaker warring parties have repeatedly utilized the proportionality barrier: in order to manipulate the adversary’s proportionality equation, immobile military objects are shielded by civilians, while mobile military equipment is intentionally sited close to civilian installations or other specifically protected locations. For example, in the recent conflict in the Middle East Hezbollah hid its rockets and military equipment in civilian neighbourhoods, and UN UnderSecretary-General Jan Egeland’s statement clearly points to the vicious circle that might be triggered by such a practice.24 Similar modes of conduct have been employed with regard to offensive tactics. The reported seizure of ambulance vehicles in order to feign protected status and thus improve the chances of attacking is a typical example, as is the fact that during the battle of Fallujah in November 2004 sixty of the city’s one hundred mosques were reportedly used as bases for military operations.25 It should be noted that, besides violating the principle of distinction, creating the false impression of legal entitlement to immunity from attack and exploiting the enemy’s confidence in that status also amount to perfidy and are prohibited as such.26 Not each and every strategy employed to circumvent superior military power by cunning, surprise, indirect approach or ruthlessness automatically constitutes prohibited conduct; it may, depending on the circumstances, amount to no more than good tactics. However, if unable to identify any military weaknesses of a superior enemy, the weaker opponent may ultimately see no other alternative than to aim for the stronger state’s soft underbelly and attack civilians or civilian objects directly, in outright violation of the principle of distinction. The series of terrorist attacks in the aftermath of 9/11, that is, the attacks in Bali, Mombasa and Djerba in 2002, Riyadh and Casablanca in 2003, Madrid in 2004, London and Cairo in 2005 and Mumbai in 2006– to mention only those which have received the greatest media attention– and the constant attacks in Afghanistan and Iraq, shows that this tendency is increasing. Avoiding the risks of attacking well-protected military installations, it enables the weaker opponent to wage an offensive war on the television screens and in the homes of the stronger state and to benefit from the repercussive effects of mass media coverage.27 The principle of proportionality Over time there is a considerable risk that in view of the aforesaid practices, international humanitarian law itself, with its clear-cut categorizations and differentiations between military and civil, may be perceived by a belligerent confronted with repeated violations by its opponent as opening the doors to a kind of war which intentionally does away with such clear demarcations.28 However, the more immediate risk is that the adversary, faced with such a misuse of the principle of distinction, could feel compelled gradually to lower the proportionality barrier. Evidently, if the use of human shields or the concealment of military equipment among civilian facilities occurs only sporadically and at random in an armed conflict, humanitarian concerns are likely to outweigh the necessity to attack using disproportionate force, whereas if such tactics are systematically employed for a strategic purpose, the enemy may feel a compelling and overriding necessity to attack irrespective of the anticipated civilian casualties and damage. Indeed, the explanation given by the Israeli government for the mounting number of civilian casualties in its recent military operations against Hezbollah in Lebanon29 confirms that systematic violation of, for example, the principle of distinction by one side during a conflict is likely adversely to affect the other side’s interpretation and application of the proportionality principle. Military necessity in asymmetric conflicts Although the concept of military necessity is invoked now and then as a separate justification for violations of the laws of war, today there can be no doubt that in contemporary international humanitarian law the element of military necessity must be balanced against the principle of humanity, and that there is no such elasticity in the laws of war that military necessity can be claimed as a reason to deviate from accepted humanitarian standards. Nevertheless, asymmetric conflict arguably entails a certain risk of the emergence of a modern-day Kriegsrason because obstacles seen as insurmountable could make both sides feel inclined and ultimately compelled vastly to expand their perception of what is necessary to overcome the enemy. Since military necessity is a component of the ius in bello equation of proportionality, to expand or overemphasize the concept of military necessity would impair the protective scope of the proportionality principle.33 The principle of military necessity is closely linked to the objectives of war. However, the objectives sought in asymmetric conflicts vary significantly from those sought in the kind of symmetric conflict constellations which the drafting fathers of the principle of military necessity had in mind. Modern authorities on the laws of war continue to refer to the definition of military necessity laid down in Article 14 of the Lieber Code, according to which ‘‘Military necessity, as understood by modern civilized nations, consists in the necessity of those measures which are indispensable for securing the ends of the war, and which are lawful according to the modern law and usages of war.’’ In view of the formulation ‘‘indispensable for securing the ends of war’’, the principle of military necessity is commonly understood to justify only that degree of force necessary to secure military defeat and the prompt submission of the enemy.37 Indeed, the Declaration of St Petersburg states as early as 1868 that ‘‘the only legitimate object which States should endeavour to accomplish during war is to weaken the military forces of the enemy’’38 and the US Army Field Manual stipulates that ‘‘The law of war … requires that belligerents refrain from employing any kind or degree of violence which is not actually necessary for military purposes’’ and defines military necessity as ‘‘that principle which justifies those measures not forbidden by international law which are indispensable for the complete submission of the enemy as soon as possible’’. Historically, the rather strict alignment of the concept of military necessity with exclusively military objectives, that is, military defeat and the prompt military submission of the enemy, is due to the fact that the concept was originally designed to restrain violence in war. Although sometimes overlooked today, restrictions on violence in war do not merely stem from balancing the principle of military necessity against the principle of humanity.41 The principle of military necessity in and of itself constitutes an important restrictive factor by prescribing that to be legitimate, violence in war first of all has to be militarily necessary.42 A gradual, clandestine widening of this concept, or simply a more lenient understanding of the factors that determine military necessity and hence the notion of military advantage, would therefore undermine the restrictive standards imposed on the use of violence in armed conflicts. Such a process seems particularly likely in view of asymmetric constellations which, owing to their complexity and intangibility, escape any military apprehension stricto sensu. For example, application of the rule of proportionality as laid down in Articles 51 and 57 of Additional Protocol I is significantly affected, even in traditional armed conflicts, by whether the notion of military advantage is understood to mean the advantage anticipated from an attack considered as a whole or merely from isolated or particular parts of the attack.43 In asymmetric constellations that elude both temporal and spatial boundaries– in other words, the traditional concept of the ‘‘battlefield’’ altogether– it would seem somewhat difficult to delineate and determine with any degree of precision what is meant by the notion of ‘‘an attack considered as a whole’’.44 More generally, as the asymmetry between belligerents increases, the distinction between political and military objectives and necessities becomes more and more blurred. Especially in conflicts such as those against al Qaeda or Hezbollah, that is, conflicts between a state or group of states and a non-state entity, that entity’s ultimate aim in using military force will be to exert pressure on the politics of the enemy rather than even attempt to achieve the latter’s military submission. Conversely, the superior party is likely to adopt a far more holistic approach, inseparably combining political and military efforts to bring about the entire political eradication or dissolution of the enemy and not just the enemy’s military submission– especially if it is battling against a non-state entity it categorizes as a terrorist organization.45 To be sure, the separation of military and political aims already present in traditional warfare has always been axiomatic to some extent, given that each and every military operation emanates from both military and political motivations.46 The so-called Christmas bombing of North Vietnam in 1972 is a typical example: even though solely military objectives within the definition thereof were targeted, its purpose was to induce the North Vietnamese government to proceed with political negotiations. Nonetheless, symmetric warfare with its identifiable battlefields in terms of space and duration did allow, at least in theory, a relatively clear separation of military and political necessities and objectives in the actual conduct of warfare. In asymmetric scenarios, however, the weaker adversary is militarily outmatched from the start, military superiority in itself is no longer a reliable guarantee for winning such conflicts and the very notions of ‘‘victory’’ or ‘‘defeat’’ thus become more and more indistinct. If these parameters remain undefined or even indefinable, straightforward determinations of what is militarily necessary are impeded. Military necessities have always been subject to change as warfare has developed, and the concept of military necessity has been flexible enough to adapt accordingly as long as that development largely resulted from technological advances in weaponry. Yet it seems doubtful whether asymmetric constellations akin to law enforcement patterns could still be grasped by and measured against the concept of military necessity,48 for the complexities and intangibility of such scenarios escape its traditionally narrow delimitations. To compromise the concept’s very narrowness, however, would mean compromising long-achieved humanitarian protections that flow directly from the concept itself and could shift the focus of the proportionality equation away from humanitarian considerations and towards military necessities.

You can only respond to the prompt using information in the context block. Discuss the concept of military necessity as outlined in this article and its relationship to contemporary asymmetric conflict. Abstract Inequality in arms, indeed, significant disparity between belligerents, has become a prominent feature of various contemporary armed conflicts. Such asymmetries, albeit not at all a new phenomenon in the field of warfare, no longer constitute a random occurrence of singular battles. As a structural characteristic of modern-day warfare asymmetric conflict structures have repercussions on the application of fundamental principles of international humanitarian law. How, for example, can the concept of military necessity, commonly understood to justify the degree of force necessary to secure military defeat of the enemy, be reconciled with a constellation in which one side in the conflict is from the outset bereft of any chance of winning the conflict militarily? Moreover, military imbalances of this scope evidently carry incentives for the inferior party to level out its inferiority by circumventing accepted rules of warfare. This article attempts tentatively to assess the repercussions this could have on the principle of reciprocity, especially the risk of the instigation of a destabilizing dynamic of negative reciprocity which ultimately could lead to a gradual intensification of a mutual disregard of international humanitarian law. Introduction With only one remaining superpower and more generally the considerable and predictably widening technological divide, an imbalance in the military capacity of warring parties has become a characteristic feature of contemporary armed conflicts. Coupled with a growing involvement of non-state entities, the disparity between belligerents is steadily increasing, and various contemporary armed conflicts appear to be more and more asymmetric in structure. Unlike the geostrategic set-up that prevailed throughout the cold war period, it is a widely perceived paradox of today’s strategic environment that military superiority may actually accentuate the threat of nuclear, biological, chemical and, generally speaking, perfidious attack. Indeed, direct attacks against civilians, hostage-taking and the use of human shields – practices that have long been outlawed in armed conflicts– have seen a revival in recent conflicts in which the far weaker party has often sought to gain a comparative advantage over the militarily superior enemy by resorting to such practices as a matter of strategy. International terrorism, although not necessarily conducted within the context of an armed conflict triggering the application of international humanitarian law (IHL), is often regarded as the epitome of such asymmetry. At the same time militarily superior parties at the other end of the spectrum have had recourse to indiscriminate attacks, illegal interrogation practices and renditions, as well as legally dubious practices such as targeted killings or hardly reviewable covert operations, in order to strike at their frequently amorphous enemy. Significant inequality of arms, that is a disparate distribution of military strength and technological capability in a given conflict, seemingly creates incentives for adversaries to resort to means and methods of warfare that undermine and are sometimes an outright violation of long-accepted standards of international humanitarian law. The war between the US-led Coalition and Iraq or the war in Afghanistan are clear examples. This tendency is reinforced if belligerents differ in nature, as in the recent conflict between Israel and Hezbollah (‘‘party of God’’)– the Lebanon-based Shia Islamic militia and political organization– or if factual asymmetries are combined with a legal asymmetry, that is in a constellation in which one side is accorded little or no legal standing. To be sure, perfect symmetries have rarely been present in war. However, the patterns of non-compliance displayed in various contemporary conflicts seem to be more structured and systematic than ever before. The present study first seeks to verify this assumption. It considers whether factual and potentially legal asymmetries do indeed constitute an incentive for breaches of international humanitarian law provisions, and, if so, how patterns of contemporary conflicts differ from those of previous conflicts that likewise exhibited discernible asymmetries. In a second step, closer scrutiny is given to the actual patterns of non-compliance in asymmetric scenarios, particularly in the light of the interplay of the principle of distinction and the principle of proportionality. Neither the term ‘‘asymmetric warfare’’ nor the sometimes synonymously employed terms ‘‘fourth-generation warfare’’ or ‘‘non-linear war’’ have thus far been concordantly defined.3 It is not the intention of this study to venture into this perhaps impenetrable terrain. Analysis shows, however, that there is a noticeable tendency in contemporary conflicts towards an increasing inequality between belligerents in terms of weaponry. While this is a long-known phenomenon in non-international armed conflicts, evaluation of the effects of military disparity in international armed conflicts continues, as does the debate over the extent to which transnational conflicts involving states and non-state entities should be subject to the laws of war. In attempting to approach this debate from a somewhat different angle, it is the overall purpose of this study to gauge the long-term repercussions that asymmetric conflict structures may have on the fundamental principles of international humanitarian law and thereby tentatively to assess the degree of asymmetry– that is, the level of military disparity between belligerents– that can still be reconciled with the legal regime applicable in times of war.5 To this end the study, in a third step, weighs the traditional concept of military necessity as laid down in the Lieber Code of 1863 against the promulgated necessities in asymmetric conflicts of our time. Even though the fundamental concepts and principles of the laws of war have been designed as prophylactic mechanisms flexible enough to outlast changes in the way in which wars are waged, it is here contended that the concept of military necessity and the principle of distinction presuppose a minimum degree of symmetry and therefore cannot be applied in subordinative constellations akin to human rights patterns, as are commonly seen in the fight against international terrorism. The vantage point for the fourth and final part of the analysis is the principle of reciprocity. As the military mismatch between conflicting parties in numerous modern armed conflicts becomes more marked, the balancing influence of the reciprocity entailed by the traditional concept of symmetric warfare is gradually being undermined.6 While the deterrent effects of an increasingly effective system of international criminal law and of media coverage and public opinion– although the last two are ambivalent factors that could also be used for the opposite purpose– could arguably help to contain non-compliant behaviour in war, international humanitarian law might thus be simultaneously bereft of its own inherent regulating mechanisms which have traditionally taken effect in the combat zone itself. The destabilizing dynamic of reciprocity could lead to a gradual and perhaps insidious erosion of the protective scope of core principles of international humanitarian law. Repeated violations of, for example, the principle of distinction by one party to a conflict are likely to induce the other side to expand its perception of what is militarily necessary, and hence proportional, when engaging in battle against such an enemy. In the final stage, and admittedly only as a worst-case scenario, an intentional and deceitful deviation from accepted standards regulating the conduct of hostilities carries the considerable risk of starting a vicious circle of ever greater negative reciprocity, in which the expectations of the warring parties are transformed into an escalating mutual noncompliance with international humanitarian law. A heightened risk of structural non-compliance? Historically, the majority of laws on international armed conflict have been designed on the basis of Clausewitz’s arguably rather Eurocentric conception of war, that is, the assumption of symmetric conflicts taking place between state armies of roughly equal military strength or at least comparable organizational structures. Throughout most of the nineteenth and twentieth centuries the dominant powers engaged in sustained arms races either to maintain a peace ensuring symmetry or to establish a tactical asymmetry vis-a `-vis their opponents as a guarantee of military victory in war.7 But quite apart from the biblical story of David and Goliath it is evident that asymmetry in the sense of military disparity is no new phenomenon.8 Nor is it a concept entirely alien to IHL. With the intrinsic disparity of the parties concerned, and even though the threshold criteria of Article 1 of Additional Protocol II to the 1949 Geneva Conventions arguably help to ensure a minimum degree of comparability between those parties, non-international armed conflicts are inherently asymmetric. It was moreover already accepted in the classic concept of symmetric warfare that the structure of conflicts could shift from symmetric to asymmetric, for by the time a conflict drew to its close and one party had gained the upper hand, the initial military balance would be out of kilter. More recently, during the Diplomatic Conference that led to the adoption of Additional Protocol I, states taking part not only acknowledged the persistence of significant disparities in military capacity but accepted that factual disparity between opponents may even lead to differing humanitarian law obligations. For example, with respect to Article 57 of Additional Protocol I on the obligation to take precautions in attack,9 the Indian delegation pointed out that according to the chosen wording the content of the due diligence obligation enshrined therein– that is, the precise identification of objectives as military or civilian– largely depended on the technical means of detection available to the belligerents.10 Despite these concerns, the present wording was accepted on the implicit understanding that because of prevailing factual disparities, international humanitarian law obligations may impose differing burdens in practice.11 Schwarzenberger has pointed out that the protective scope of the laws of war has historically been the strongest in duel-type wars between comparable belligerents that were fought for limited purposes, such as the Crimean War of 1853–6 or the Franco-German War of 1870–1, whereas in major wars such as the Napoleonic wars or the two world wars of the twentieth century– wars that were fought to the bitter end– the weaker side often tended to seek short-term advantages by violating the laws of war.12 Indeed, violations of the laws of war have occurred in nearly every case in which IHL has been applicable,13 and the risk that one party may order or connive in large-scale violations of the laws of war in order to gain a tempting advantage or stave off in some way an otherwise threatening defeat has always hovered over the legal regime intended to regulate conduct in armed conflicts.14 However, in symmetric constellations such instances have tended to remain marginal, often limited to the final stages of a war and confined to individual battles in which defeat seemed inevitable, or resort to perfidy or similarly prohibited tactics was perceived as guaranteeing an immediate tactical breakthrough in what was otherwise a military stalemate. As a result of the evident disparate military capabilities of opponents in certain contemporary conflicts, incentives for violations of IHL seem in comparison to have reached a new height. Non-compliance with the provisions of IHL is no longer a random event, confined to temporally and spatially limited incidents within a conflict, but has become a recurrent structural feature that characterizes many of today’s armed conflicts from the outset. The reason is that, faced with an enemy of overwhelming technological superiority, the weaker party ab initio has no chance of winning the war militarily. Figures from the recent war against Iraq illustrate this imbalance of power and capacity quite well. While the Iraqi air force reportedly never left the ground, Coalition forces flew rather more than 20,000 sorties, during which only one fixed-wing aircraft and only seven aircraft in all were lost to hostile fire.15 Evidence of a comparable inequality in the military capability of belligerents will probably become available in the aftermath of the recent conflict in Lebanon. Without anticipating the more detailed analysis below, it should be noted that the Iraqi army’s widespread infringements during the international conflict against the US-led Coalition, as well as Hezbollah’s indiscriminate attacks, stem to a significant extent from the blatant inequality in weaponry. Practices employed by the Iraqi army included recourse to human shields, abuse of the red cross and red crescent emblems, the use of anti-personnel mines and the placing of military objects in protected areas such as mosques and hospitals. Clearly, there is thus an elevated risk that the militarily inferior party, unable to identify any military weaknesses of its superior opponent, may feel compelled systematically to offset the enemy’s superiority by resorting to means and methods of warfare outside the realm of international humanitarian law. At the same time the use of ‘‘unthinkable’’ tactics as well as the tactical circumvention of accepted IHL standards creates a barrier that cannot be readily overcome by military superiority alone. Apart from the ongoing hostilities in Iraq, the tactics employed by the Somali tribal leader Farah Aydid in 1993 are a good example of this. In conventional terms, his forces were no match for heavily armed and technologically sophisticated airborne US troops. However, by using primitive weapons and communication systems– which reportedly varied from cellular phones to tribal drums– and by resorting to ‘‘unthinkable’’ tactics and to ‘‘barbaric’’ acts perpetrated for the benefit of the news media, the militia convinced the leadership of the United States that despite the military backwardness of the Somali forces the price of involvement in Somalia was very high. In the course of the war against Iraq the use of cluster munitions in populated areas, as well as the alleged use of white phosphorus and the continued recourse by US and British forces to ‘‘decapitation’’ strikes that caused high numbers of civilian casualties, partly constituted indiscriminate attacks and arguably a failure to take ‘‘all feasible precautions’’ as required by IHL. There are thus apparent incentives for both sides to give increasing priority, potentially to the detriment of humanitarian considerations, to the necessities of such a kind of warfare. Patterns of non-compliance: the interplay between the principle of distinction and the principle of proportionality Recent conflict patterns suggest that militarily inferior parties, in order to evade attack by an enemy of insurmountable superiority or to level out inequalities in military power, tend in particular to instrumentalize and intentionally manipulate the principle of distinction. This manipulation may occur in different ways.18 Similarly, superior parties are likely to lower the barrier of proportionality in response to a systematic misuse of the principle of distinction and their resulting inability to tackle the enemy effectively. The following description of potential strategies that belligerents may feel compelled to adopt when faced with overwhelming odds or systematic deviations from accepted legal rules is merely intended to facilitate understanding of likely patterns of non-compliance and does not claim to be comprehensive. It is part of the very nature of asymmetric strategies that they are impossible to predict. The principle of distinction As a defensive strategy when facing a technologically superior enemy it is essential, but ever more difficult, to stay out of reach and conceal one’s presence as a combatant. Hiding in mountainous areas, caves, underground facilities and tunnels is one way. However, another means of doing so quickly and efficiently is readily available by virtue of the provisions of IHL themselves. In view of the various forms of protection accorded to civilians, assuming civilian guise is an easy way to evade the enemy and, unlike the more traditional guerrilla-style tactics of hiding underground or in inaccessible areas, it cannot be countered by the development of advanced discovery technologies. Indeed, in order to keep Coalition forces from identifying them as enemies, that is as legitimate targets, many Iraqi soldiers in the recent war reportedly quite often discarded their uniforms. This is not a prohibited tactic, as long as such practices are not used to launch an attack under the cover of protected status; according to Article 4 of the Third Geneva Convention the absence of any fixed distinctive sign recognizable at a distance merely leads to the loss of combatant status and the corresponding privileges. Still, despite its legality such a practice will, if employed as a matter of strategy, create considerable uncertainty about a person’s status and thus subtly erode the effectiveness of the fundamental and, in the words of the International Court of Justice (ICJ), intransgressible principle of distinction. Evidently the notion of distinction, that is, the legally prescribed invulnerability of certain persons and objects, can if manipulated offer manifold loopholes for the evasion of attack.22 The dividing line between legal tactics and illegitimate practices is easily crossed. The misuse of protective emblems for the concealment of military objects is a case in point, and the marking of the Ba’ath Party building in Basra with the ICRC emblem is a flagrant example of such tactics.23 To protect military objects whose nature could not be so readily concealed, weaker warring parties have repeatedly utilized the proportionality barrier: in order to manipulate the adversary’s proportionality equation, immobile military objects are shielded by civilians, while mobile military equipment is intentionally sited close to civilian installations or other specifically protected locations. For example, in the recent conflict in the Middle East Hezbollah hid its rockets and military equipment in civilian neighbourhoods, and UN UnderSecretary-General Jan Egeland’s statement clearly points to the vicious circle that might be triggered by such a practice.24 Similar modes of conduct have been employed with regard to offensive tactics. The reported seizure of ambulance vehicles in order to feign protected status and thus improve the chances of attacking is a typical example, as is the fact that during the battle of Fallujah in November 2004 sixty of the city’s one hundred mosques were reportedly used as bases for military operations.25 It should be noted that, besides violating the principle of distinction, creating the false impression of legal entitlement to immunity from attack and exploiting the enemy’s confidence in that status also amount to perfidy and are prohibited as such.26 Not each and every strategy employed to circumvent superior military power by cunning, surprise, indirect approach or ruthlessness automatically constitutes prohibited conduct; it may, depending on the circumstances, amount to no more than good tactics. However, if unable to identify any military weaknesses of a superior enemy, the weaker opponent may ultimately see no other alternative than to aim for the stronger state’s soft underbelly and attack civilians or civilian objects directly, in outright violation of the principle of distinction. The series of terrorist attacks in the aftermath of 9/11, that is, the attacks in Bali, Mombasa and Djerba in 2002, Riyadh and Casablanca in 2003, Madrid in 2004, London and Cairo in 2005 and Mumbai in 2006– to mention only those which have received the greatest media attention– and the constant attacks in Afghanistan and Iraq, shows that this tendency is increasing. Avoiding the risks of attacking well-protected military installations, it enables the weaker opponent to wage an offensive war on the television screens and in the homes of the stronger state and to benefit from the repercussive effects of mass media coverage.27 The principle of proportionality Over time there is a considerable risk that in view of the aforesaid practices, international humanitarian law itself, with its clear-cut categorizations and differentiations between military and civil, may be perceived by a belligerent confronted with repeated violations by its opponent as opening the doors to a kind of war which intentionally does away with such clear demarcations.28 However, the more immediate risk is that the adversary, faced with such a misuse of the principle of distinction, could feel compelled gradually to lower the proportionality barrier. Evidently, if the use of human shields or the concealment of military equipment among civilian facilities occurs only sporadically and at random in an armed conflict, humanitarian concerns are likely to outweigh the necessity to attack using disproportionate force, whereas if such tactics are systematically employed for a strategic purpose, the enemy may feel a compelling and overriding necessity to attack irrespective of the anticipated civilian casualties and damage. Indeed, the explanation given by the Israeli government for the mounting number of civilian casualties in its recent military operations against Hezbollah in Lebanon29 confirms that systematic violation of, for example, the principle of distinction by one side during a conflict is likely adversely to affect the other side’s interpretation and application of the proportionality principle. Military necessity in asymmetric conflicts Although the concept of military necessity is invoked now and then as a separate justification for violations of the laws of war, today there can be no doubt that in contemporary international humanitarian law the element of military necessity must be balanced against the principle of humanity, and that there is no such elasticity in the laws of war that military necessity can be claimed as a reason to deviate from accepted humanitarian standards. Nevertheless, asymmetric conflict arguably entails a certain risk of the emergence of a modern-day Kriegsrason because obstacles seen as insurmountable could make both sides feel inclined and ultimately compelled vastly to expand their perception of what is necessary to overcome the enemy. Since military necessity is a component of the ius in bello equation of proportionality, to expand or overemphasize the concept of military necessity would impair the protective scope of the proportionality principle.33 The principle of military necessity is closely linked to the objectives of war. However, the objectives sought in asymmetric conflicts vary significantly from those sought in the kind of symmetric conflict constellations which the drafting fathers of the principle of military necessity had in mind. Modern authorities on the laws of war continue to refer to the definition of military necessity laid down in Article 14 of the Lieber Code, according to which ‘‘Military necessity, as understood by modern civilized nations, consists in the necessity of those measures which are indispensable for securing the ends of the war, and which are lawful according to the modern law and usages of war.’’ In view of the formulation ‘‘indispensable for securing the ends of war’’, the principle of military necessity is commonly understood to justify only that degree of force necessary to secure military defeat and the prompt submission of the enemy.37 Indeed, the Declaration of St Petersburg states as early as 1868 that ‘‘the only legitimate object which States should endeavour to accomplish during war is to weaken the military forces of the enemy’’38 and the US Army Field Manual stipulates that ‘‘The law of war … requires that belligerents refrain from employing any kind or degree of violence which is not actually necessary for military purposes’’ and defines military necessity as ‘‘that principle which justifies those measures not forbidden by international law which are indispensable for the complete submission of the enemy as soon as possible’’. Historically, the rather strict alignment of the concept of military necessity with exclusively military objectives, that is, military defeat and the prompt military submission of the enemy, is due to the fact that the concept was originally designed to restrain violence in war. Although sometimes overlooked today, restrictions on violence in war do not merely stem from balancing the principle of military necessity against the principle of humanity.41 The principle of military necessity in and of itself constitutes an important restrictive factor by prescribing that to be legitimate, violence in war first of all has to be militarily necessary.42 A gradual, clandestine widening of this concept, or simply a more lenient understanding of the factors that determine military necessity and hence the notion of military advantage, would therefore undermine the restrictive standards imposed on the use of violence in armed conflicts. Such a process seems particularly likely in view of asymmetric constellations which, owing to their complexity and intangibility, escape any military apprehension stricto sensu. For example, application of the rule of proportionality as laid down in Articles 51 and 57 of Additional Protocol I is significantly affected, even in traditional armed conflicts, by whether the notion of military advantage is understood to mean the advantage anticipated from an attack considered as a whole or merely from isolated or particular parts of the attack.43 In asymmetric constellations that elude both temporal and spatial boundaries– in other words, the traditional concept of the ‘‘battlefield’’ altogether– it would seem somewhat difficult to delineate and determine with any degree of precision what is meant by the notion of ‘‘an attack considered as a whole’’.44 More generally, as the asymmetry between belligerents increases, the distinction between political and military objectives and necessities becomes more and more blurred. Especially in conflicts such as those against al Qaeda or Hezbollah, that is, conflicts between a state or group of states and a non-state entity, that entity’s ultimate aim in using military force will be to exert pressure on the politics of the enemy rather than even attempt to achieve the latter’s military submission. Conversely, the superior party is likely to adopt a far more holistic approach, inseparably combining political and military efforts to bring about the entire political eradication or dissolution of the enemy and not just the enemy’s military submission– especially if it is battling against a non-state entity it categorizes as a terrorist organization.45 To be sure, the separation of military and political aims already present in traditional warfare has always been axiomatic to some extent, given that each and every military operation emanates from both military and political motivations.46 The so-called Christmas bombing of North Vietnam in 1972 is a typical example: even though solely military objectives within the definition thereof were targeted, its purpose was to induce the North Vietnamese government to proceed with political negotiations. Nonetheless, symmetric warfare with its identifiable battlefields in terms of space and duration did allow, at least in theory, a relatively clear separation of military and political necessities and objectives in the actual conduct of warfare. In asymmetric scenarios, however, the weaker adversary is militarily outmatched from the start, military superiority in itself is no longer a reliable guarantee for winning such conflicts and the very notions of ‘‘victory’’ or ‘‘defeat’’ thus become more and more indistinct. If these parameters remain undefined or even indefinable, straightforward determinations of what is militarily necessary are impeded. Military necessities have always been subject to change as warfare has developed, and the concept of military necessity has been flexible enough to adapt accordingly as long as that development largely resulted from technological advances in weaponry. Yet it seems doubtful whether asymmetric constellations akin to law enforcement patterns could still be grasped by and measured against the concept of military necessity,48 for the complexities and intangibility of such scenarios escape its traditionally narrow delimitations. To compromise the concept’s very narrowness, however, would mean compromising long-achieved humanitarian protections that flow directly from the concept itself and could shift the focus of the proportionality equation away from humanitarian considerations and towards military necessities.

"================ <TEXT PASSAGE> ======= [context document] ================ <QUESTION> ======= [user request] ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Please summarize this article about new a eczema treatment. I would like bullet points with the important key features of the treatment. Include details about the researched probiotic and what it does for the skin. Keep the answer under 500 words/

NIAID research has led to the availability of a new over-the-counter topical eczema probiotic. The probiotic is based on the discovery by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, that bacteria present on healthy skin called Roseomonas mucosa can safely relieve eczema symptoms in adults and children. R. mucosa-based topical interventions could simplify or complement current eczema management, when used in consultation with an individual's healthcare provider. A milestone for eczema sufferers, the availability of an R. mucosa-based probiotic is the result of seven years of scientific discovery and research in NIAID's Laboratory of Clinical Immunology and Microbiology (LCIM). Eczema-;also known as atopic dermatitis-;is a chronic inflammatory skin condition that affects approximately 20% of children and 10% of adults worldwide. The condition is characterized by dry, itchy skin that can compromise the skin's barrier, which functions to retain moisture and keep out allergens. This can make people with eczema more vulnerable to bacterial, viral and fungal skin infections. R. mucosa is a commensal bacterium, meaning it occurs naturally as part of a typical skin microbiome. Individuals with eczema experience imbalances in the microbiome and are deficient in certain skin lipids (oils). NIAID researchers demonstrated that R. mucosa can help restore those lipids. Scientists led by Ian Myles, M.D., M.P.H., chief of the LCIM Epithelial Research Unit, found specific strains of R. mucosa reduced eczema-related skin inflammation and enhanced the skin's natural barrier function in both adults and children. To arrive at this finding, Dr. Myles and colleagues spearheaded a spectrum of translational research on R. mucosa. They isolated and cultured R. mucosa in the laboratory, conducted preclinical (laboratory/animal) and clinical (human) studies, and made the bacteria available for commercial, non-therapeutic development. The R. mucosa-based probiotic released this week is formulated by Skinesa and called Defensin. In Phase 1/2 open-label and Phase 2 blinded, placebo-controlled clinical studies, most people experienced greater than 75% improvement in eczema severity following application of R. mucosa. Improvement was seen on all treated skin sites, including the inner elbows, inner knees, hands, trunk and neck. The researchers also observed improvement in skin barrier function. Additionally, most participants needed fewer corticosteroids to manage their eczema, experienced less itching, and reported a better quality of life following R. mucosa therapy. These benefits persisted after treatment ended: therapeutic R. mucosa strains remained on the skin for up to eight months in study participants who were observed for that duration. eBook: How to Implement Colony Picking Workflows eBook This eBook aims to assist scientists in selecting the most suitable automated colony-picking solution, taking into account the requirements for high throughput, various applications, and key challenges of the process. Download the latest edition To expand the potential use of R. mucosa, NIAID will conduct an additional clinical trial to generate further evidence on its efficacy in reducing eczema symptoms. Those data could form the basis of an application to the Food and Drug Administration to enable the product to be regulated as a nonprescription drug and made accessible to a broader population of people with eczema. Study results are expected in 2024. Source:

"================ <TEXT PASSAGE> ======= NIAID research has led to the availability of a new over-the-counter topical eczema probiotic. The probiotic is based on the discovery by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, that bacteria present on healthy skin called Roseomonas mucosa can safely relieve eczema symptoms in adults and children. R. mucosa-based topical interventions could simplify or complement current eczema management, when used in consultation with an individual's healthcare provider. A milestone for eczema sufferers, the availability of an R. mucosa-based probiotic is the result of seven years of scientific discovery and research in NIAID's Laboratory of Clinical Immunology and Microbiology (LCIM). Eczema-;also known as atopic dermatitis-;is a chronic inflammatory skin condition that affects approximately 20% of children and 10% of adults worldwide. The condition is characterized by dry, itchy skin that can compromise the skin's barrier, which functions to retain moisture and keep out allergens. This can make people with eczema more vulnerable to bacterial, viral and fungal skin infections. R. mucosa is a commensal bacterium, meaning it occurs naturally as part of a typical skin microbiome. Individuals with eczema experience imbalances in the microbiome and are deficient in certain skin lipids (oils). NIAID researchers demonstrated that R. mucosa can help restore those lipids. Scientists led by Ian Myles, M.D., M.P.H., chief of the LCIM Epithelial Research Unit, found specific strains of R. mucosa reduced eczema-related skin inflammation and enhanced the skin's natural barrier function in both adults and children. To arrive at this finding, Dr. Myles and colleagues spearheaded a spectrum of translational research on R. mucosa. They isolated and cultured R. mucosa in the laboratory, conducted preclinical (laboratory/animal) and clinical (human) studies, and made the bacteria available for commercial, non-therapeutic development. The R. mucosa-based probiotic released this week is formulated by Skinesa and called Defensin. In Phase 1/2 open-label and Phase 2 blinded, placebo-controlled clinical studies, most people experienced greater than 75% improvement in eczema severity following application of R. mucosa. Improvement was seen on all treated skin sites, including the inner elbows, inner knees, hands, trunk and neck. The researchers also observed improvement in skin barrier function. Additionally, most participants needed fewer corticosteroids to manage their eczema, experienced less itching, and reported a better quality of life following R. mucosa therapy. These benefits persisted after treatment ended: therapeutic R. mucosa strains remained on the skin for up to eight months in study participants who were observed for that duration. eBook: How to Implement Colony Picking Workflows eBook This eBook aims to assist scientists in selecting the most suitable automated colony-picking solution, taking into account the requirements for high throughput, various applications, and key challenges of the process. Download the latest edition To expand the potential use of R. mucosa, NIAID will conduct an additional clinical trial to generate further evidence on its efficacy in reducing eczema symptoms. Those data could form the basis of an application to the Food and Drug Administration to enable the product to be regulated as a nonprescription drug and made accessible to a broader population of people with eczema. Study results are expected in 2024. Source: https://www.news-medical.net/news/20240626/NIAID-scientists-discover-probiotic-treatment-for-eczema.aspx ================ <QUESTION> ======= Please summarize this article about new a eczema treatment. I would like bullet points with the important key features of the treatment. Include details about the researched probiotic and what it does for the skin. Keep the answer under 500 words/ ================ <TASK> ======= You are an expert in question answering. Your task is to reply to a query or question, based only on the information provided by the user. It should only use information in the article provided."

Only use the information provided to you in the prompt, NEVER use external resources or prior knowledge. Responses should be exactly two paragraphs in length. If you don't know something because it's not provided in the document, say "Don't know - information not found." Bullet points or sentence fragments should never be used unless specifically requested. Focus on common-sense, obvious conclusions with specific factual support from the prompt.

My patient, patient X, has a 3,000 kilocalorie per day diet. I deem the kilocalorie intake to be healthy, due to his profession of blacksmith, however I am concerned that he may not be following the most up-to-date guidelines issued by the federal Dietary Guidelines Advisory Committee. Here is his current weekly diet: 1 kilogram bacon 2 dozen eggs 500 g butter 500 g lard 4 kilograms cheese, assorted 7 carrots 1/2 kilogram spinach 2 kilograms roast beef 1 baguette (large) 1/2 kilogram mushrooms 3 extra-sweet vidalia onions 4 liters organic sulfite-free red wine 1 free-range chicken assorted sauces, gravies, and condiments Detailed analysis shows that patient X consumes 300 calories, which is 10% of his daily total, of added sugars per day from all sources. To what extent is Patient X's diet aligned with the DGAC policy recommendations referenced in the included document?

Which Key Issues Were Raised by Stakeholders with the 2015 DGAC’s Report? The DGAC’s report addressed many issues of concern to public health, nutrition, and agricultural stakeholders. HHS and USDA received over 29,000 written comments during the 75-day comment period, as well as 73 oral comments at a March 2015 public meeting.25 Stakeholders flagged several issues with the 2015 DGAC’s report, particularly with the scope of the DGAC’s recommendations, the process by which the DGAC made its conclusions and recommendations, and concerns over several specific recommendations.26 Scope One concern noted by stakeholders with the DGAC’s report was its scope, with some maintaining that the committee exceeded the scope of its charter by making certain policy recommendations. For example, although the 2015 DGAC’s report noted that no food groups need to be entirely eliminated to improve food sustainability outcomes, the DGAC concluded that individuals should eat less red and processed meat in favor of a plant-based diet, as “a diet higher in plant-based foods, such as vegetables, fruits, whole grains, legumes, nuts, and seeds, and lower in calories and animal-based foods is more health promoting and is associated with less environmental impact than is the current U.S. diet.” The DGAC added that due to high consumption of animal-based foods (e.g., meat, eggs, and dairy products) and low intake of plant-based foods, the average U.S. diet may have a large impact on the environment in terms of increased Greenhouse Gas (GHG) emissions, land use, water use, and energy use. In addition, the DGAC made several policy recommendations that raised concern among some stakeholders, including FDA revision of the Nutrition Facts label to include a mandatory declaration for added sugars, in both grams and teaspoons per serving, as well as a % daily value (DV);27 alignment of federal nutrition assistance programs (e.g., SNAP and WIC) with the DGA; and use of economic and tax policies to encourage the production and consumption of healthy foods and to reduce consumption of unhealthy foods (e.g., by taxing sugar-sweetened beverages, snack foods, and desserts, and by restricting marketing of certain foods to children and teens).28 Some Members of Congress have said that the DGAC “had neither the expertise, evidence, nor charter” to make recommendations about matters of sustainability and tax policy,29 and this 24 Scientific Report of the 2015 Dietary Guidelines Advisory Committee, February 19, 2015, see http://www.health.gov/ dietaryguidelines/. 25 Testimony of Secretary of USDA Tom Vilsack, October 7, 2015, Committee on Agriculture Hearing, U.S. House of Representatives. 26 Please note that this is not an exhaustive list of all the concerns surrounding the DGAC report. 27 Per FDA’s proposed supplemental rule, this %DV would be based on the recommendation that the daily intake of calories from added sugars not exceed 10% of total calories. For a 2,000 calorie diet, 10% would equate to approximately 50 grams of added sugar per day (10% of 2,000 equals 200 calories from added sugar; there are 4 calories per gram of sugar, so 200 calories divided by 4 equals 50 grams of added sugar per day). 28 Scientific Report of the 2015 DGAC, Part D: Chapter 6: Cross-Cutting Topics of Public Health Importance; see http://health.gov/dietaryguidelines/2015-scientific-report/pdfs/scientific-report-of-the-2015-dietary-guidelinesadvisory-committee.pdf. 29 Letter from various Members of Congress to Secretaries Vilsack and Burwell, March 31, 2015; see concern has been reiterated by some meat industry groups.30 Meanwhile, others have supported the discussion surrounding sustainability, saying that it is important to have an understanding of how food production affects the environment.31 In response to these concerns, the HHS and USDA Secretaries determined that issues of sustainability and tax policy would not be part of the final policy document and that the DGA would “remain within the scope of our mandate in the 1990 National Nutrition Monitoring and Related Research Act (P.L. 101-445, NNMRRA), which is to provide ‘nutritional and dietary information and guidelines’ ... ‘based on the preponderance of the scientific and medical knowledge.’” 32 Process Another stakeholder concern with the 2015 DGAC’s report was the process used to evaluate the evidence. After the 2005 edition of the DGA, HHS and USDA committed to using an evidencebased, systematic review methodology (i.e., the NEL) to support the development of the 2010 DGAC report, and the same process was expected to be used in the development of the 2015 DGAC report. The 2015 DGAC used the NEL to answer approximately 27% of its questions, relying on existing sources of evidence (e.g., existing reports and systematic reviews) to answer another 45%, and data analyses and food pattern modeling analyses to answer an additional 30%. 33 This approach is in contrast to the 2010 DGAC, which used the NEL to answer the majority of its research questions.34 According to the 2015 DGAC, the majority of the scientific community now regularly uses systematic reviews, so unlike the 2010 DGAC, the 2015 DGAC was able to rely more heavily on existing sources of evidence (e.g., existing systematic reviews, meta-analyses, and reports) and to avoid duplicative efforts.35 Some criticized this use of existing reviews, questioning the scientific rigor and objectivity of the advisory report. For example, some argued that the 2015 DGAC bypassed the NEL process for certain issues (e.g., added sugars) and “almost solely used pre-existing and hand-picked http://agriculture.house.gov/uploadedfiles/ag_dietaryguidelineslettertosecsvilsackburwell.pdf. 30 National Cattleman’s Beef Association, NCBA Urges Secretaries to Reject Dietary Guidelines Advisory Committee’s Flawed Recommendations May 8, 2015; see http://www.beefusa.org/newsreleases1.aspx?newsid= 4912#sthash.gecc7dMk.dpuf. 31 A Aubrey, “New Dietary Guidelines Will not Include Sustainability Goal,” NPR, October 13, 2015; see http://www.npr.org/sections/thesalt/2015/10/06/446369955/new-dietary-guidelines-will-not-include-sustainability-goal. 32 Secretaries Vilsack and Burwell, “2015 Dietary Guidelines: Giving You the Tools You Need to Make Healthy Choices,” USDA blog, October 6, 2015; see http://blogs.usda.gov/2015/10/06/2015-dietary-guidelines-giving-you-thetools-you-need-to-make-healthy-choices/. 33 These numbers were taken directly from the Scientific Report of the 2015 DGAC, Part C: Methodology. They do not add up to 100% for reasons unknown to CRS, but one explanation may be that multiple sources were used to answer certain questions. 34 Report of the 2010 DGAC on the Dietary Guidelines for Americans, 2010, Part A: Executive Summary, page 1. 35 Scientific Report of the 2015 DGAC, Part C: Methodology; see http://health.gov/dietaryguidelines/2015-scientificreport/pdfs/scientific-report-of-the-2015-dietary-guidelines-advisory-committee.pdf.

System Instruction: Only use the information provided to you in the prompt, NEVER use external resources or prior knowledge. Responses should be exactly two paragraphs in length. If you don't know something because it's not provided in the document, say "Don't know - information not found." Bullet points or sentence fragments should never be used unless specifically requested. Focus on common-sense, obvious conclusions with specific factual support from the prompt. Question: My patient, patient X, has a 3,000 kilocalorie per day diet. I deem the kilocalorie intake to be healthy, due to his profession of blacksmith, however I am concerned that he may not be following the most up-to-date guidelines issued by the federal Dietary Guidelines Advisory Committee. Here is his current weekly diet: 1 kilogram bacon 2 dozen eggs 500 g butter 500 g lard 4 kilograms cheese, assorted 7 carrots 1/2 kilogram spinach 2 kilograms roast beef 1 baguette (large) 1/2 kilogram mushrooms 3 extra-sweet vidalia onions 4 liters organic sulfite-free red wine 1 free-range chicken assorted sauces, gravies, and condiments Detailed analysis shows that patient X consumes 300 calories, which is 10% of his daily total, of added sugars per day from all sources. To what extent is Patient X's diet aligned with the DGAC policy recommendations referenced in the included document? Context: Which Key Issues Were Raised by Stakeholders with the 2015 DGAC’s Report? The DGAC’s report addressed many issues of concern to public health, nutrition, and agricultural stakeholders. HHS and USDA received over 29,000 written comments during the 75-day comment period, as well as 73 oral comments at a March 2015 public meeting.25 Stakeholders flagged several issues with the 2015 DGAC’s report, particularly with the scope of the DGAC’s recommendations, the process by which the DGAC made its conclusions and recommendations, and concerns over several specific recommendations.26 Scope One concern noted by stakeholders with the DGAC’s report was its scope, with some maintaining that the committee exceeded the scope of its charter by making certain policy recommendations. For example, although the 2015 DGAC’s report noted that no food groups need to be entirely eliminated to improve food sustainability outcomes, the DGAC concluded that individuals should eat less red and processed meat in favor of a plant-based diet, as “a diet higher in plant-based foods, such as vegetables, fruits, whole grains, legumes, nuts, and seeds, and lower in calories and animal-based foods is more health promoting and is associated with less environmental impact than is the current U.S. diet.” The DGAC added that due to high consumption of animal-based foods (e.g., meat, eggs, and dairy products) and low intake of plant-based foods, the average U.S. diet may have a large impact on the environment in terms of increased Greenhouse Gas (GHG) emissions, land use, water use, and energy use. In addition, the DGAC made several policy recommendations that raised concern among some stakeholders, including FDA revision of the Nutrition Facts label to include a mandatory declaration for added sugars, in both grams and teaspoons per serving, as well as a % daily value (DV);27 alignment of federal nutrition assistance programs (e.g., SNAP and WIC) with the DGA; and use of economic and tax policies to encourage the production and consumption of healthy foods and to reduce consumption of unhealthy foods (e.g., by taxing sugar-sweetened beverages, snack foods, and desserts, and by restricting marketing of certain foods to children and teens).28 Some Members of Congress have said that the DGAC “had neither the expertise, evidence, nor charter” to make recommendations about matters of sustainability and tax policy,29 and this 24 Scientific Report of the 2015 Dietary Guidelines Advisory Committee, February 19, 2015, see http://www.health.gov/ dietaryguidelines/. 25 Testimony of Secretary of USDA Tom Vilsack, October 7, 2015, Committee on Agriculture Hearing, U.S. House of Representatives. 26 Please note that this is not an exhaustive list of all the concerns surrounding the DGAC report. 27 Per FDA’s proposed supplemental rule, this %DV would be based on the recommendation that the daily intake of calories from added sugars not exceed 10% of total calories. For a 2,000 calorie diet, 10% would equate to approximately 50 grams of added sugar per day (10% of 2,000 equals 200 calories from added sugar; there are 4 calories per gram of sugar, so 200 calories divided by 4 equals 50 grams of added sugar per day). 28 Scientific Report of the 2015 DGAC, Part D: Chapter 6: Cross-Cutting Topics of Public Health Importance; see http://health.gov/dietaryguidelines/2015-scientific-report/pdfs/scientific-report-of-the-2015-dietary-guidelinesadvisory-committee.pdf. 29 Letter from various Members of Congress to Secretaries Vilsack and Burwell, March 31, 2015; see concern has been reiterated by some meat industry groups.30 Meanwhile, others have supported the discussion surrounding sustainability, saying that it is important to have an understanding of how food production affects the environment.31 In response to these concerns, the HHS and USDA Secretaries determined that issues of sustainability and tax policy would not be part of the final policy document and that the DGA would “remain within the scope of our mandate in the 1990 National Nutrition Monitoring and Related Research Act (P.L. 101-445, NNMRRA), which is to provide ‘nutritional and dietary information and guidelines’ ... ‘based on the preponderance of the scientific and medical knowledge.’” 32 Process Another stakeholder concern with the 2015 DGAC’s report was the process used to evaluate the evidence. After the 2005 edition of the DGA, HHS and USDA committed to using an evidencebased, systematic review methodology (i.e., the NEL) to support the development of the 2010 DGAC report, and the same process was expected to be used in the development of the 2015 DGAC report. The 2015 DGAC used the NEL to answer approximately 27% of its questions, relying on existing sources of evidence (e.g., existing reports and systematic reviews) to answer another 45%, and data analyses and food pattern modeling analyses to answer an additional 30%. 33 This approach is in contrast to the 2010 DGAC, which used the NEL to answer the majority of its research questions.34 According to the 2015 DGAC, the majority of the scientific community now regularly uses systematic reviews, so unlike the 2010 DGAC, the 2015 DGAC was able to rely more heavily on existing sources of evidence (e.g., existing systematic reviews, meta-analyses, and reports) and to avoid duplicative efforts.35 Some criticized this use of existing reviews, questioning the scientific rigor and objectivity of the advisory report. For example, some argued that the 2015 DGAC bypassed the NEL process for certain issues (e.g., added sugars) and “almost solely used pre-existing and hand-picked http://agriculture.house.gov/uploadedfiles/ag_dietaryguidelineslettertosecsvilsackburwell.pdf. 30 National Cattleman’s Beef Association, NCBA Urges Secretaries to Reject Dietary Guidelines Advisory Committee’s Flawed Recommendations May 8, 2015; see http://www.beefusa.org/newsreleases1.aspx?newsid= 4912#sthash.gecc7dMk.dpuf. 31 A Aubrey, “New Dietary Guidelines Will not Include Sustainability Goal,” NPR, October 13, 2015; see http://www.npr.org/sections/thesalt/2015/10/06/446369955/new-dietary-guidelines-will-not-include-sustainability-goal. 32 Secretaries Vilsack and Burwell, “2015 Dietary Guidelines: Giving You the Tools You Need to Make Healthy Choices,” USDA blog, October 6, 2015; see http://blogs.usda.gov/2015/10/06/2015-dietary-guidelines-giving-you-thetools-you-need-to-make-healthy-choices/. 33 These numbers were taken directly from the Scientific Report of the 2015 DGAC, Part C: Methodology. They do not add up to 100% for reasons unknown to CRS, but one explanation may be that multiple sources were used to answer certain questions. 34 Report of the 2010 DGAC on the Dietary Guidelines for Americans, 2010, Part A: Executive Summary, page 1. 35 Scientific Report of the 2015 DGAC, Part C: Methodology; see http://health.gov/dietaryguidelines/2015-scientificreport/pdfs/scientific-report-of-the-2015-dietary-guidelines-advisory-committee.pdf.

You must generate a response using only this provided document. Do not use any other outside source to support your claims. If you are unable to answer the request using the supporting document only, then you must respond with "please support more relevant documents so that I may answer your request accurately".

How does hormonal imbalance in women affect mood and what can be done to minimize these affects?

MOOD SWINGS IN WOMEN DUE TO HORMONE IMBALANCE A mood swing is defined as “an abrupt and apparently unaccountable change of mood.” Mood swings can be triggered by any number of events or situations, but in many cases, the root cause of a mood swing is a shift in hormone levels. One minute you are feeling elated and happy, but the next you are expressing anger and hostility. Mood swings are common in women who are experiencing hormonal fluctuations due to physiological events, such menstruation or menopause. Chronic mood swings can significantly affect a woman’s health and are often the result of a hormonal imbalance. The good news is that mood swings is another hormonal imbalance symptom that could be treated safely and effectively with hormone therapy. What Causes Mood Swings? Mood swings can be a side effect of lifestyle choices, life events or physiological changes, including: Stress It’s no secret that stress influences mood. Stress has a number of effects on the body— physical and psychological. Hormones and neurotransmitters that regulate mood can be affected by stress levels. Too much stress can cause cortisol levels to rise, leading to fatigue, poor sleep and appetite changes, further impacting changes in mood and behavior. Psychiatric Issues Mood disorders are not always related to a hormonal imbalance. In some cases, psychological disorders or mental health conditions may be to blame. ADHD (attention deficit hyperactive disorder), bipolar disorder, panic disorder and depression are just a few examples of psychological issues that may cause mood swings. PMS (premenstrual syndrome) For many women, uncomfortable symptoms can occur approximately one to two weeks before menstruation. This period of time is known as PMS, or premenstrual syndrome. Premenstrual mood swings are just one symptoms and may be influenced by other common symptoms, including bloating, fatigue, changes in appetite and depression. The cause of these symptoms is related to shifts in progesterone and estrogen levels, which rise and fall throughout the full menstrual cycle. PMDD (premenstrual dysmorphic disorder) PMDD, or premenstrual dysmorphic disorder, is a more severe form of PMS, affecting approximately 8 percent of premenopausal women. The symptoms of PMDD are similar to those experienced with PMS, but mood swings tend to be more extreme, along with other emotions, such irritability, sadness, and anxiety. The cause of PMDD is not well understood, but it is speculated that it is the effect of an abnormal response of the brain to hormonal shifts that occur before menstruation leading to a deficiency in the neurotransmitter, serotonin. Menopause Mood swings are one of the most common symptoms of menopause. During perimenopause, severe mood swings can occur due to hormonal shifts affecting estrogen and progesterone. The hormonal shifts are generally more extreme in the earlier phases of the transition into menopause. Other menopausal symptoms, such as hot flashes and night sweats, can cause undue stress, poor sleep and anxiety that can lead to mood swings as well. Thyroid Dysfunction Thyroid dysfunction can influence mood and cause mood swings. Hypothyroidism can be the result of low thyroid hormone and high cortisol levels. This can affect sleep, energy and appetite, all of which can impact mood. Hormonal Imbalance In general, out of balance hormones can affect mood. Estrogen and progesterone are well-known for their role in female physiology and fluctuate frequently throughout the female life cycle. However, other hormones may become imbalanced due to age or illness and cause mood swings. For example, low testosterone in women can impact energy, weight, and sex drive. High cortisol can lead to anxiety, sleeplessness, and weight gain. Any of these factors can cause mood swings simply due to the effects on a woman’`s lifestyle or overall health and wellbeing. How Mood Swings Affect Women&’s Health** Mood swings can damage relationships, interfere with work productivity and limit social interactions. This can negatively affect your mental health and become a source of stress—both of which can increase the risk of more serious disease. If your mood swings are more than occasional bouts of moodiness before your period or after a particularly bad day, it might be time to seek help. Identifying the root cause of your mood swings with the help of a qualified professional can you ensure you get the most effective treatment. Female Hormone Balance Therapy for Mood Swings Mood swings are not something any woman should ignore. If you are experiencing frequent mood swings, seek help from a qualified professional. If your mood swings are related to a hormonal imbalance, you are likely experiencing other symptoms or events in your lifecycle. For example, women who are perimenopausal will likely be experiencing hot flashes, foggy thinking or joint pain along with mood swings. If you have a thyroid disorder, you may notice that your mood swings are accompanied by feeling tired all the time, a change in appetite and an inability to regulate your body temperature. These are signs that your mood swings may be related to a hormonal imbalance. Advanced lab testing can help pinpoint which hormones are out of balance and may causing your mood swings and other symptoms. Following lab testing, you can meet with one of the expert physicians of the BodyLogicMD network for a one-on-one consultation. Each practitioner is highly trained and specializes in hormone health and balance. He/she will review your lab results, discuss your symptoms and medical history, as well as come to understand how your life has been affected by hormone imbalance. Your doctor will partner with you to develop a comprehensive treatment plan that will correct any hormone imbalance safely and effectively to help relieve you from the unwelcome symptoms, like mood swings. Your treatment plan may include bioidentical hormone replacement therapy to restore hormone balance, along with nutritional guidance, fitness recommendations, stressreduction techniques and pharmaceutical-grade supplements. Each element in your treatment plan will be designed to fit your lifestyle, while ensuring your medical needs are met and your wellness goals are achieved.

You must generate a response using only this provided document. Do not use any other outside source to support your claims. If you are unable to answer the request using the supporting document only, then you must respond with "please support more relevant documents so that I may answer your request accurately". How does hormonal imbalance in women affect mood and what can be done to minimize these affects? MOOD SWINGS IN WOMEN DUE TO HORMONE IMBALANCE A mood swing is defined as “an abrupt and apparently unaccountable change of mood.” Mood swings can be triggered by any number of events or situations, but in many cases, the root cause of a mood swing is a shift in hormone levels. One minute you are feeling elated and happy, but the next you are expressing anger and hostility. Mood swings are common in women who are experiencing hormonal fluctuations due to physiological events, such menstruation or menopause. Chronic mood swings can significantly affect a woman’s health and are often the result of a hormonal imbalance. The good news is that mood swings is another hormonal imbalance symptom that could be treated safely and effectively with hormone therapy. What Causes Mood Swings? Mood swings can be a side effect of lifestyle choices, life events or physiological changes, including: Stress It’s no secret that stress influences mood. Stress has a number of effects on the body— physical and psychological. Hormones and neurotransmitters that regulate mood can be affected by stress levels. Too much stress can cause cortisol levels to rise, leading to fatigue, poor sleep and appetite changes, further impacting changes in mood and behavior. Psychiatric Issues Mood disorders are not always related to a hormonal imbalance. In some cases, psychological disorders or mental health conditions may be to blame. ADHD (attention deficit hyperactive disorder), bipolar disorder, panic disorder and depression are just a few examples of psychological issues that may cause mood swings. PMS (premenstrual syndrome) For many women, uncomfortable symptoms can occur approximately one to two weeks before menstruation. This period of time is known as PMS, or premenstrual syndrome. Premenstrual mood swings are just one symptoms and may be influenced by other common symptoms, including bloating, fatigue, changes in appetite and depression. The cause of these symptoms is related to shifts in progesterone and estrogen levels, which rise and fall throughout the full menstrual cycle. PMDD (premenstrual dysmorphic disorder) PMDD, or premenstrual dysmorphic disorder, is a more severe form of PMS, affecting approximately 8 percent of premenopausal women. The symptoms of PMDD are similar to those experienced with PMS, but mood swings tend to be more extreme, along with other emotions, such irritability, sadness, and anxiety. The cause of PMDD is not well understood, but it is speculated that it is the effect of an abnormal response of the brain to hormonal shifts that occur before menstruation leading to a deficiency in the neurotransmitter, serotonin. Menopause Mood swings are one of the most common symptoms of menopause. During perimenopause, severe mood swings can occur due to hormonal shifts affecting estrogen and progesterone. The hormonal shifts are generally more extreme in the earlier phases of the transition into menopause. Other menopausal symptoms, such as hot flashes and night sweats, can cause undue stress, poor sleep and anxiety that can lead to mood swings as well. Thyroid Dysfunction Thyroid dysfunction can influence mood and cause mood swings. Hypothyroidism can be the result of low thyroid hormone and high cortisol levels. This can affect sleep, energy and appetite, all of which can impact mood. Hormonal Imbalance In general, out of balance hormones can affect mood. Estrogen and progesterone are well-known for their role in female physiology and fluctuate frequently throughout the female life cycle. However, other hormones may become imbalanced due to age or illness and cause mood swings. For example, low testosterone in women can impact energy, weight, and sex drive. High cortisol can lead to anxiety, sleeplessness, and weight gain. Any of these factors can cause mood swings simply due to the effects on a woman’`s lifestyle or overall health and wellbeing. How Mood Swings Affect Women&’s Health** Mood swings can damage relationships, interfere with work productivity and limit social interactions. This can negatively affect your mental health and become a source of stress—both of which can increase the risk of more serious disease. If your mood swings are more than occasional bouts of moodiness before your period or after a particularly bad day, it might be time to seek help. Identifying the root cause of your mood swings with the help of a qualified professional can you ensure you get the most effective treatment. Female Hormone Balance Therapy for Mood Swings Mood swings are not something any woman should ignore. If you are experiencing frequent mood swings, seek help from a qualified professional. If your mood swings are related to a hormonal imbalance, you are likely experiencing other symptoms or events in your lifecycle. For example, women who are perimenopausal will likely be experiencing hot flashes, foggy thinking or joint pain along with mood swings. If you have a thyroid disorder, you may notice that your mood swings are accompanied by feeling tired all the time, a change in appetite and an inability to regulate your body temperature. These are signs that your mood swings may be related to a hormonal imbalance. Advanced lab testing can help pinpoint which hormones are out of balance and may causing your mood swings and other symptoms. Following lab testing, you can meet with one of the expert physicians of the BodyLogicMD network for a one-on-one consultation. Each practitioner is highly trained and specializes in hormone health and balance. He/she will review your lab results, discuss your symptoms and medical history, as well as come to understand how your life has been affected by hormone imbalance. Your doctor will partner with you to develop a comprehensive treatment plan that will correct any hormone imbalance safely and effectively to help relieve you from the unwelcome symptoms, like mood swings. Your treatment plan may include bioidentical hormone replacement therapy to restore hormone balance, along with nutritional guidance, fitness recommendations, stressreduction techniques and pharmaceutical-grade supplements. Each element in your treatment plan will be designed to fit your lifestyle, while ensuring your medical needs are met and your wellness goals are achieved.

Respond using only the information contained in the text. The response must be no more than 250 words.

According to the document, what are some limitations of big data sets when conducting research?

Collectively, this research suggests that big data offers both new potential discriminatory harms and new potential solutions to discriminatory harms. To maximize the benefits and limit the harms, companies should consider the questions raised by research in this area. These questions include the following: 1. How representative is your data set? Workshop participants and researchers note that the data sets, on which all big data analysis relies, may be missing information about certain populations, e.g., individuals who are more careful about revealing information about themselves, who are less involved in the formal economy, who have unequal access or less fluency in technology resulting in a digital divide148 or data desert,149 or whose behaviors are simply not observed because they are believed to be less profitable constituencies.150 Recent examples demonstrate the impact of missing information about particular populations on data analytics. For example, Hurricane Sandy generated more than twenty million tweets between October 27 and November 1, 2012.151 If organizations were to use this data to determine where services should be deployed, the people who needed services the most may not have received them. The greatest number of tweets about Hurricane Sandy came from Manhattan, creating the illusion that Manhattan was the hub of the disaster. Very few messages originated from more severely affected locations, such as Breezy Point, Coney Island, and Rockaway—areas with lower levels of smartphone ownership and Twitter usage. As extended power blackouts drained batteries and limited cellular access, even fewer tweets came from the worst hit areas. As one researcher noted, “data are assumed to accurately reflect the social world, but there are significant gaps, with little or no signal coming from particular communities.”152 Organizations have developed ways to overcome this issue. For example, the city of Boston developed an application called Street Bump that utilizes smartphone features such as GPS feeds to collect and report to the city information about road conditions, including potholes. However, after the release of the application, the Street Bump team recognized that because lower income individuals may be less likely to carry smartphones, the data was likely not fully representative of all road conditions. If the city had continued relying on the biased data, it might have skewed road services to higher income neighborhoods. The team addressed this problem by issuing its application to city workers who service the whole city and supplementing the data with that from the public.153 This example demonstrates why it is important to consider the digital divide and other issues of underrepresentation and overrepresentation in data inputs before launching a product or service in order to avoid skewed and potentially unfair ramifications. 2. Does your data model account for biases? While large data sets can give insight into previously intractable challenges, hidden biases at both the collection and analytics stages of big data’s life cycle could lead to disparate impact.154 Researchers have noted that big data analytics “can reproduce existing patterns of discrimination, inherit the prejudice of prior decision-makers, or simply reflect the widespread biases that persist in society.”155 For example, if an employer uses big data analytics to synthesize information gathered on successful existing employees to define a “good employee candidate,” the employer could risk incorporating previous discrimination in employment decisions into new employment decisions.156 Even prior to the widespread use of big data, there is some evidence of the use of data leading to the reproduction of existing biases. For example, one researcher has noted that a hospital developed a computer model to help identify “good medical school applicants” based on performance levels of previous and existing students, but, in doing so, the model reproduced prejudices in prior admission decisions.157 Companies can also design big data algorithms that learn from human behavior; these algorithms may “learn” to generate biased results. For example, one academic found that Reuters and Google queries for names identified by researchers to be associated with African-Americans were more likely to return advertisements for arrest records than for names identified by researchers to be associated with white Americans.158 The academic concluded that determining why this discrimination was occurring was beyyond the scope of her research, but reasoned that search engines’ algorithms may learn to prioritize arrest record ads for searches of names associated with African-Americans if people click on such ads more frequently than other ads.159 This could reinforce the display of such ads and perpetuate the cycle. Companies should therefore think carefully about how the data sets and the algorithms they use have been generated. Indeed, if they identify potential biases in the creation of these data sets or the algorithms, companies should develop strategies to overcome them. As noted above, Google changed its interview and hiring process to ask more behavioral questions and to focus less on academic grades after discovering that replicating its existing definitions of a “good employee” was resulting in a homogeneous tech workforce.160 More broadly, companies are starting to recognize that if their big data algorithms only consider applicants from “top tier” colleges to help them make hiring decisions, they may be incorporating previous biases in college admission decisions.161 As in the examples discussed above, companies should develop ways to use big data to expand the pool of qualified applicants they will consider.162 3. How accurate are your predictions based on big data? Some researchers have also found that big data analysis does not give sufficient attention to traditional applied statistics issues, thus leading to incorrect results and predictions.163 They note that while big data is very good at detecting correlations, it does not explain which correlations are meaningful.164 A prime example that demonstrates the limitations of big data analytics is Google Flu Trends, a machinelearning algorithm for predicting the number of flu cases based on Google search terms. To predict the spread of influenza across the United States, the Google team analyzed the top fifty million search terms for indications that the flu had broken out in particular locations. While, at first, the algorithms appeared to create accurate predictions of where the flu was more prevalent, it generated highly inaccurate estimates over time.165 This could be because the algorithm failed to take into account certain variables. For example, the algorithm may not have taken into account that people would be more likely to search for flu-related terms if the local news ran a story on a flu outbreak, even if the outbreak occurred halfway around the world. As one researcher has noted, Google Flu Trends demonstrates that a “theory-free analysis of mere correlations is inevitably fragile. If you have no idea what is behind a correlation, you have no idea what might cause that correlation to break down.”166 As another example, workshop participants discussed the fact that lenders can improve access to credit by using non-traditional indicators, e.g., rental or utility bill payment history.167 Consumers, however, have the right to withhold rent if their landlord does not provide heat or basic sanitation services. In these instances, simply compiling rental payment history would not necessarily demonstrate whether the person is a good credit risk.168 In some cases, these sources of inaccuracies are unlikely to have significant negative effects on consumers. For example, it may be that big data analytics shows that 30 percent of consumers who buy diapers will respond to an ad for baby formula. That response rate may be enough for a marketer to find it worthwhile to send buyers of diapers an advertisement for baby formula. The 70 percent of consumers who buy diapers but are not interested in formula can disregard the ad or discard it at little cost. Similarly, consumers who are interested in formula and who do not buy diapers are unlikely to be substantially harmed because they did not get the ad. On the other hand, if big data analytics are used as the basis for access to credit, housing, or other similar benefits, the potential effects on consumers from inaccuracies could be substantial.169 For example, suppose big data analytics predict that people who do not participate in social media are 30 percent more likely to be identity thieves, leading a fraud detection tool to flag such people as “risky.” Suppose further that a wireless company uses this tool and requires “risky” people to submit additional documentation before they can obtain a cell phone contract. These people may not be able to obtain the contract if they do not have the required documentation.

Respond using only the information contained in the text. The response must be no more than 250 words. Collectively, this research suggests that big data offers both new potential discriminatory harms and new potential solutions to discriminatory harms. To maximize the benefits and limit the harms, companies should consider the questions raised by research in this area. These questions include the following: 1. How representative is your data set? Workshop participants and researchers note that the data sets, on which all big data analysis relies, may be missing information about certain populations, e.g., individuals who are more careful about revealing information about themselves, who are less involved in the formal economy, who have unequal access or less fluency in technology resulting in a digital divide148 or data desert,149 or whose behaviors are simply not observed because they are believed to be less profitable constituencies.150 Recent examples demonstrate the impact of missing information about particular populations on data analytics. For example, Hurricane Sandy generated more than twenty million tweets between October 27 and November 1, 2012.151 If organizations were to use this data to determine where services should be deployed, the people who needed services the most may not have received them. The greatest number of tweets about Hurricane Sandy came from Manhattan, creating the illusion that Manhattan was the hub of the disaster. Very few messages originated from more severely affected locations, such as Breezy Point, Coney Island, and Rockaway—areas with lower levels of smartphone ownership and Twitter usage. As extended power blackouts drained batteries and limited cellular access, even fewer tweets came from the worst hit areas. As one researcher noted, “data are assumed to accurately reflect the social world, but there are significant gaps, with little or no signal coming from particular communities.”152 Organizations have developed ways to overcome this issue. For example, the city of Boston developed an application called Street Bump that utilizes smartphone features such as GPS feeds to collect and report to the city information about road conditions, including potholes. However, after the release of the application, the Street Bump team recognized that because lower income individuals may be less likely to carry smartphones, the data was likely not fully representative of all road conditions. If the city had continued relying on the biased data, it might have skewed road services to higher income neighborhoods. The team addressed this problem by issuing its application to city workers who service the whole city and supplementing the data with that from the public.153 This example demonstrates why it is important to consider the digital divide and other issues of underrepresentation and overrepresentation in data inputs before launching a product or service in order to avoid skewed and potentially unfair ramifications. 2. Does your data model account for biases? While large data sets can give insight into previously intractable challenges, hidden biases at both the collection and analytics stages of big data’s life cycle could lead to disparate impact.154 Researchers have noted that big data analytics “can reproduce existing patterns of discrimination, inherit the prejudice of prior decision-makers, or simply reflect the widespread biases that persist in society.”155 For example, if an employer uses big data analytics to synthesize information gathered on successful existing employees to define a “good employee candidate,” the employer could risk incorporating previous discrimination in employment decisions into new employment decisions.156 Even prior to the widespread use of big data, there is some evidence of the use of data leading to the reproduction of existing biases. For example, one researcher has noted that a hospital developed a computer model to help identify “good medical school applicants” based on performance levels of previous and existing students, but, in doing so, the model reproduced prejudices in prior admission decisions.157 Companies can also design big data algorithms that learn from human behavior; these algorithms may “learn” to generate biased results. For example, one academic found that Reuters and Google queries for names identified by researchers to be associated with African-Americans were more likely to return advertisements for arrest records than for names identified by researchers to be associated with white Americans.158 The academic concluded that determining why this discrimination was occurring was beyyond the scope of her research, but reasoned that search engines’ algorithms may learn to prioritize arrest record ads for searches of names associated with African-Americans if people click on such ads more frequently than other ads.159 This could reinforce the display of such ads and perpetuate the cycle. Companies should therefore think carefully about how the data sets and the algorithms they use have been generated. Indeed, if they identify potential biases in the creation of these data sets or the algorithms, companies should develop strategies to overcome them. As noted above, Google changed its interview and hiring process to ask more behavioral questions and to focus less on academic grades after discovering that replicating its existing definitions of a “good employee” was resulting in a homogeneous tech workforce.160 More broadly, companies are starting to recognize that if their big data algorithms only consider applicants from “top tier” colleges to help them make hiring decisions, they may be incorporating previous biases in college admission decisions.161 As in the examples discussed above, companies should develop ways to use big data to expand the pool of qualified applicants they will consider.162 3. How accurate are your predictions based on big data? Some researchers have also found that big data analysis does not give sufficient attention to traditional applied statistics issues, thus leading to incorrect results and predictions.163 They note that while big data is very good at detecting correlations, it does not explain which correlations are meaningful.164 A prime example that demonstrates the limitations of big data analytics is Google Flu Trends, a machinelearning algorithm for predicting the number of flu cases based on Google search terms. To predict the spread of influenza across the United States, the Google team analyzed the top fifty million search terms for indications that the flu had broken out in particular locations. While, at first, the algorithms appeared to create accurate predictions of where the flu was more prevalent, it generated highly inaccurate estimates over time.165 This could be because the algorithm failed to take into account certain variables. For example, the algorithm may not have taken into account that people would be more likely to search for flu-related terms if the local news ran a story on a flu outbreak, even if the outbreak occurred halfway around the world. As one researcher has noted, Google Flu Trends demonstrates that a “theory-free analysis of mere correlations is inevitably fragile. If you have no idea what is behind a correlation, you have no idea what might cause that correlation to break down.”166 As another example, workshop participants discussed the fact that lenders can improve access to credit by using non-traditional indicators, e.g., rental or utility bill payment history.167 Consumers, however, have the right to withhold rent if their landlord does not provide heat or basic sanitation services. In these instances, simply compiling rental payment history would not necessarily demonstrate whether the person is a good credit risk.168 In some cases, these sources of inaccuracies are unlikely to have significant negative effects on consumers. For example, it may be that big data analytics shows that 30 percent of consumers who buy diapers will respond to an ad for baby formula. That response rate may be enough for a marketer to find it worthwhile to send buyers of diapers an advertisement for baby formula. The 70 percent of consumers who buy diapers but are not interested in formula can disregard the ad or discard it at little cost. Similarly, consumers who are interested in formula and who do not buy diapers are unlikely to be substantially harmed because they did not get the ad. On the other hand, if big data analytics are used as the basis for access to credit, housing, or other similar benefits, the potential effects on consumers from inaccuracies could be substantial.169 For example, suppose big data analytics predict that people who do not participate in social media are 30 percent more likely to be identity thieves, leading a fraud detection tool to flag such people as “risky.” Suppose further that a wireless company uses this tool and requires “risky” people to submit additional documentation before they can obtain a cell phone contract. These people may not be able to obtain the contract if they do not have the required documentation. According to the document, what are some limitations of big data sets when conducting research?

Simplify the language used so it's easier to understand. Only pull information from the provided document.

What are the pros and cons mentioned in this reviews?

Dependable Mic I do sound for small bands and these mics are very dependable and sound great. The work for vocals and instruments. A good buy. by Aj from Salinas, Ca on November 29, 2023 Music background: Dj/Live Sound Best Dynamic Mic ever This mix is amazing. It will always be a classic. Still putting it through its paces but it sounds great. by VenoMUZIK from Columbus, OH on August 10, 2023 Music background: Singer/songwriter, composer, producer Great sounding mic for the money Have been impressed with the pickup and sound quality of these mics compared to some of the other mics I use by Lee Yoritomo from Montgomery Village, MD on February 16, 2024 Shure SM 58 Microphone.. No matter what type of venue you do you're SM 58 microphone is always ready to go no batteries to change out and it's always spot on! by Sweetwater Customer from Alaska on February 6, 2024 Shure SM 58 Microphone.. No matter what type of venue you do you're SM 58 microphone is always ready to go no batteries to change out and it's always spot on! by Sweetwater Customer from Kenai, Alaska on February 6, 2024 Twenty years ago I quickly acquired a Realistic microphone to use when I served as the disc jockey at wedding receptions and class reunions. When it recently rolled off the table at an event and broke into a few pieces I wanted to order a replacement. I purchased the Shure SM 58 Handheld Dynamic Vocal Microphone (based on a co-worker's recommendation). When a microphone was needed at a recent festival I gave it the first testing. It was much lower and less powerful than my previous "cheaper" microphone (which had been purchased at a local Radio Shack affiliate). I am currently involved with testing it at my workplace to see if it is truly defective or needs some sort of power boost to effectively broadcast voices loud enough through my gear. parts not interchangeable By daniel graves from California on May 10, 2017 Music Background: performer Many reviews will tell you that the sms58S is just the sm58 with a switch added. But when trying to exchange the microphone element between the two, I discovered that the parts are not interchangeable. The thread count is different on the collar and different on the mike head, with different rubber gaskets, the diameter of the mike elements are different, and wiring colors are different. Possibly this is a difference in year of manufacture, One mike is a year old, the other unknown but at least 5yrs old (these mikes have been around since the 60's, so who knows). One other difference is that the SMS58 is more insulated,and less prone to noise from handling the mike (or did they just make the the housing quieter in the older models? Shure SM58 By Timothy Connelly from Pacifin North West on December 22, 2023 Music Background: Garage band, Open Mic, Gigs The mic works well, however I wish it had a on/off switch' On another matter, I was hoping to review the purchase of my JBL EONONE 1 Perhaps it is my age (72), but I find it very confusing in regards to the operation of the unit. I realize Sweetwater is not the manufacturer of the JBL EONONE, however it would be great if Sweetwater could produce an owners manual that a senior citizen could understand. I have managed to program 2 out of 5 channels. I have not solved all of the special affects including reverb, chorus and delay, Maybe for a younger consumer who is better educated in the "tech" world , this is not a problem. I can promise you for this consumer, it is more than frustrating. Sincerely Timothy Connelly

Simplify the language used so it's easier to understand. Only pull information from the provided document. What are the pros and cons mentioned in this reviews? Dependable Mic I do sound for small bands and these mics are very dependable and sound great. The work for vocals and instruments. A good buy. by Aj from Salinas, Ca on November 29, 2023 Music background: Dj/Live Sound Best Dynamic Mic ever This mix is amazing. It will always be a classic. Still putting it through its paces but it sounds great. by VenoMUZIK from Columbus, OH on August 10, 2023 Music background: Singer/songwriter, composer, producer Great sounding mic for the money Have been impressed with the pickup and sound quality of these mics compared to some of the other mics I use by Lee Yoritomo from Montgomery Village, MD on February 16, 2024 Shure SM 58 Microphone.. No matter what type of venue you do you're SM 58 microphone is always ready to go no batteries to change out and it's always spot on! by Sweetwater Customer from Alaska on February 6, 2024 Shure SM 58 Microphone.. No matter what type of venue you do you're SM 58 microphone is always ready to go no batteries to change out and it's always spot on! by Sweetwater Customer from Kenai, Alaska on February 6, 2024 Twenty years ago I quickly acquired a Realistic microphone to use when I served as the disc jockey at wedding receptions and class reunions. When it recently rolled off the table at an event and broke into a few pieces I wanted to order a replacement. I purchased the Shure SM 58 Handheld Dynamic Vocal Microphone (based on a co-worker's recommendation). When a microphone was needed at a recent festival I gave it the first testing. It was much lower and less powerful than my previous "cheaper" microphone (which had been purchased at a local Radio Shack affiliate). I am currently involved with testing it at my workplace to see if it is truly defective or needs some sort of power boost to effectively broadcast voices loud enough through my gear. parts not interchangeable By daniel graves from California on May 10, 2017 Music Background: performer Many reviews will tell you that the sms58S is just the sm58 with a switch added. But when trying to exchange the microphone element between the two, I discovered that the parts are not interchangeable. The thread count is different on the collar and different on the mike head, with different rubber gaskets, the diameter of the mike elements are different, and wiring colors are different. Possibly this is a difference in year of manufacture, One mike is a year old, the other unknown but at least 5yrs old (these mikes have been around since the 60's, so who knows). One other difference is that the SMS58 is more insulated,and less prone to noise from handling the mike (or did they just make the the housing quieter in the older models? Shure SM58 By Timothy Connelly from Pacifin North West on December 22, 2023 Music Background: Garage band, Open Mic, Gigs The mic works well, however I wish it had a on/off switch' On another matter, I was hoping to review the purchase of my JBL EONONE 1 Perhaps it is my age (72), but I find it very confusing in regards to the operation of the unit. I realize Sweetwater is not the manufacturer of the JBL EONONE, however it would be great if Sweetwater could produce an owners manual that a senior citizen could understand. I have managed to program 2 out of 5 channels. I have not solved all of the special affects including reverb, chorus and delay, Maybe for a younger consumer who is better educated in the "tech" world , this is not a problem. I can promise you for this consumer, it is more than frustrating. Sincerely Timothy Connelly