text:
Q: How does parquet determine which encoding to use? Context:

*

*I have two identical datasets (say Left and Right) with 112 parquet files in each dataset.

*These parquet files were created using Hive, by converting delimited flat files.

*The process used to create the delimited flat files files is slightly different between left and right processes.

*I noticed a significant size difference between both datasets, even though the content in them is exactly the same. Left dataset is 400GB and Right dataset is 420GB.

*When I checked the Parquet schema using parquet-tools, I noticed different encoding was used for left and right datasets as shown (for one column) below:

Left:
column_a:  INT64 SNAPPY DO:0 FPO:4 SZ:5179987/6161135/1.19 VC:770100 ENC:PLAIN,RLE,BIT_PACKED

Right:
column_a:  INT64 SNAPPY DO:0 FPO:4 SZ:3040269/5671813/1.87 VC:782499 ENC:BIT_PACKED,PLAIN,RLE,PLAIN_DICTIONARY

My Question:
How does parquet determine what encoding type to use and what could have made parquet choose different encoding? Is it something we can control using a Hive / Spark config?

A: I think that the mailing list message here with reply here has the best answer that I'm aware of. In short, you can't directly control the encoding that Parquet uses for any given column. There are some things that may help to improve it a bit, like specifying that you wish to write a Parquet Version 2 file rather than a Parquet Version 1 file, but that's not precise control. There may be something that can be done, but it would probably involve diving deep into the internals of a Parquet implementation.

A: The only writer that I found until now that allows you to define encoding for each column is the Arrow Parquet Writer. I do not found  way in the ParquetWriter API in the Java repository.

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Home » Featured, News, Opinion, Posts, Transfers
Is this player the perfect Philippe Coutinho replacement?
Jack Hallows
Jack Hallows provides a profile of reported transfer target Nabil Fekir and looks at where the Frenchman would fit in at Liverpool should he sign.
I'm pretty excited about this one I have to admit.
Liverpool have recently been linked with a whole host of names from around Europe as the summer window draws ever closer but one seemingly gaining traction quicker than you can say "top four race" is Lyon's Nabil Fekir.
The Frenchman is alleged to be Klopp's first choice 'replacement' for Brazilian playmaker Philippe Coutinho and certain French outlets have even gone as far as to suggest it's a done deal, with the Reds reportedly set to pay £62m for his services.
The truth behind all these rumours will remain a mystery until the player is shown donning Liverpool red at Melwood for the next addition in the club's signing day vlog series but whether he signs or not, the links shouldn't be surprising.
Directly, Liverpool haven't really missed Philippe Coutinho's presence since he left for Barcelona in January. In fact, you could probably argue quite successfully that they've become a better all-round team.
Klopp has been blessed with goal threats all over the pitch and opposition teams are unsure whether to focus primarily on stopping Salah, Firmino or Mané. The end result? Whoever they leave free, generally scores.
However, one issue with having opted to not replace the Brazilian directly has been that of squad depth. The Reds simply don't have quality players waiting in the wings to be rotated into the starting XI and recent performances have highlighted just how tired this group of players is growing.
Imagine then, being able to turn to the bench during a frustrating 0-0 and instead of having to turn to Danny Ings or Dominic Solanke, Klopp points to a man who has managed 22 goals and 8 assists this season.
Fekir can play in practically any of the attacking positions and would provide an alternative to each and every one of Salah, Firmino, Mané and even Oxlade-Chamberlain. He's generally been at his most comfortable for Lyon playing through the middle of the park in an attacking midfield type role but we've seen time and time again just how good Klopp is at fitting a player into his system rather than adapting his tactics to fit one player.
With 22 goals and 8 assists in all competitions this season, there's no doubting that the Frenchman would replace some of the firepower lost by selling Coutinho in January.
Our deadly trio have done brilliantly in his absence but the added creativity (2 key passes per 90) and goal threat (a goal every 134 minutes, 3 shots per 90) that the 24-year-old would bring to our squad would only serve to further boost our chances of smothering opposition teams before they even have a chance to breathe.
He can also take a decent free kick which is something that has admittedly been lacking since Coutinho's sale.
If the Reds have the opportunity to add another top class attacker who scores, creates, can dribble past opposing players like they're stuck in treacle and would inject extra pace, versatility and most importantly, quality, into our squad then really, this should be a no-brainer.
Of course, a reported £62m is a lot of money to be paying for a player who, while exciting, isn't a guaranteed starter in this Liverpool outfit. Personally, as versatile as he is, I struggle to see exactly what specific role he'd play but that's the beauty of this Liverpool team under this manager. We're unpredictable.
Tags:Jürgen KloppNabil FekirPhilippe CoutinhoTransfers
John W. Henry confirms Liverpool will be active in the summer transfer market
Three things we learned in Liverpool v Man United

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text:
UAE: Five men defraud woman of Dh149,000 by posing as bank employees in phone scam
The woman said she gave them her personal data after they said that they wanted the information to update her bank account details, they then withdrew the money
Ismail Sebugwaawo
Published: Sun 27 Nov 2022, 8:36 AM
Five young men who took Dh149,000 from a woman after taking her personal information in a phone scam have been instructed to pay the money back to the victim.
The Al Ain Civil Court of First Instance issued the ruling ordering the men to return the woman's money.
Official court documents stated that the woman had filed a lawsuit against the men demanding that they return the Dh149,000 they withdrew from her bank account after stealing her details.
She explained that one of the men phoned her and told her that he and his colleagues were employees of the bank where she had an account.
The woman said she gave them her personal data after they said that they wanted the information to update her bank account. They then withdrew Dh149,000 from her bank account.
Dubai: Four jailed for running gambling operation out of rented villa
Massage card scams on the rise in UAE: How cops are clamping down on the menace
The Al Ain Criminal Court had earlier convicted the men of fraud and ordered them to return the money to woman, but they refused.
This prompted her to file a civil lawsuit against them demanding that they pay back her money.
After hearing from all parties, the civil court judge ordered the five men to jointly return the Dh149,000 they defrauded from the woman. The men were also told to pay for the woman's legal expenses.
UAE authorities and banks have always told people to be on high alert if asked to disclose personal information, particularly over the phone or by messaging services such as WhatsApp.
Authorities say bank employees will never ask customers for personal details over the phone.
Abu Dhabi Police earlier said people should not share sensitive financial details such as bank details or one-time password (OTP) and CVV codes, and should not click on unknown links.
ismail@khaleejtimes.com


Earlier this year, Toyota's usage of AI for its Rav4 Marketing Campaign got the jaws dropping and the eyes widening. IBM's Watson had struck again – a Machine Learning (ML) program that used an algorithm to generate ad scripts! The campaign is an example of how Toyota agency-of-record Saatchi & Saatchi Los Angeles is using what it calls "creative programmatic."
The agency wanted to connect the Toyota's Rav4 crossover to the favorite activities of individual consumers but in an unpredictable way. So, Saatchi fed Watson the world's top 1,000 activities - like biking, dancing, and cooking - and asked Watson to pair two activities that had low probabilities of being matched. The agency then used the pairings to create 300 unique videos, which targeted at users on Facebook and Instagram.
This is an example of how AI has already made inroads in the sphere of digital marketing, where global brands are competing with each other. AI, once a science fiction fantasy, then a laugh-inducing project, is now increasingly becoming a cornerstone of emerging technologies across various industries. Unsurprisingly, the tech-savvy world of digital marketing is already beginning to put AI to great use to automate and improve current marketing processes.
There are copious amounts of data available everywhere, which is, in fact, making the processes more cumbersome, if done manually. This makes human behavior to abandon data and go by intuition. This is the kind of scenario where AI emerges as a powered tool as intuition won't lead one to astute results.
A digital marketer constantly goes through these questions – Who should I reach out to? What should I send? When should I schedule my posts? Over what channel will my posts have greater reach? Comprehensive answers to these questions are looked with an aim to create engagement amongst customers and further lead to growth, fostering sales and finally build a brand!
Today, there are many new AI and machine learning services developing which mean that these techniques are now open to every business. The purpose of this guide is to cut through the hype and noise around these powerful technologies and show what you can put in place today to boost your business results. It provides models and strategies to successfully run these projects, and gives examples and case studies of how the technology is used in businesses of all sizes, so you can understand how you can use it for your business.
Facebook has a service that uses AI to present you ads on the basis of your likes and dislikes; Netflix presents you viewing recommendations on the basis of your tastes in past history and even the major e-commerce portals use AI as a tool to feed your page on the basis of your lifestyle and previous buys. With programmatic accounting for 67% of all global display ads in 2017, AI is needed more than ever to ensure the increased volume of ads does not affect the quality of ads. Marketers can maintain positive brand perception and engage with newer audiences with AI's help. However, brands should know that it is not about taking advantage of AI, but it is about learning to work with a system that thinks like a human.
Though one can still view certain ads, which might be redundant, it is good to know that this problem won't continue for long.
Individual advertising is an ongoing project and is worth the effort. Traditional audience segmentation is dying. People want and need to receive personalized treatment, and AI + ML works on the basis of customer preference and will continue to generate and serve people's needs in the future with the help of artificial intelligence.
AI is centrally focused on taking algorithm of search engine to a next level i.e., helping the customer reach the destination in a shorter period with need-to-know- information.
For example, when you Google specific words - a mix of information including location, search history, time of day, and context is analyzed to present you with a list of results. Brands can't take advantage of this AI but instead can create content that Google considers valuable. This is because of Google's AI. Rank Brain isn't an algorithm you can just throw keywords at. It's learning to read on-site content and queries just like a human. The results Google presents are the best answers to a user's question. Voice queries from personal AIs such as Google Home, Amazon Echo, and the just-announced Apple HomePad are also being analyzed through Google.
Chatbots effortlessly engage with your audience through an inbuilt messaging platform. Services like Uber use Facebook's AI chatbot to help users request rides and receive driver updates without leaving Facebook Messenger. Chatbots help by uniquely promoting your brand or providing relevant data on your audience. This data can help brands market certain products, discover what needs fixing, and how to better target your desired audience.
In traditional marketing, it was a cumbersome task to collect data of various sample sizes, filter it, and further analyze it to try and make sense of it. AI helps to penetrate deep in the data, which is easily extractable from various sources and further help digital marketers in reaching the right audience through segmentation and based on various preferences – age, lifestyle, choices, income, profession, etc.
Consumers can browse through various AI empowered suggestions websites from the luxury of sitting in their homes!
Facebook has already started using AI in other ways like lookalike audience. With this feature, you can find new customers, which resemble your present audience. Lookalike audience takes your current audience, adds on top of it the additional data you provide, and then further uses that intelligence to target lookalike audiences, i.e. new audience with shared interests. This tool opens your doors to consumers who are unaware of your brand and helps build a future strategy for your target market.
Due to an exponential increase in online activity, even huge corporations are protective of their brand image as any virus can damage their reputation. AI tracks any abnormal activity in the algorithm, that is different from a regular pattern and alerts the digital marketers of a threat.
As an example, Facebook is using deep learning technology to better detect human faces, and with their DeepText program, Facebook is cracking the code of computers understanding the nuances of language. For marketers, this means more segmentation that is accurate and targeting for ads.
Sales and Marketing were traditionally considered as separate departments in organizations. However, modern practices have broken that barrier and are constantly working towards bridging that barrier between these two. AI can do this very easily and as it has access to huge amount of data. AI can help analyze inbound communications and interpret them to make actions based on the past behaviors. AI can help filter the vast amounts of data to focus the probability of a conversion, which a human can take very long time to do.
Whether we like it for the ease AI brings into our lives, as digital marketers and as consumers both, or we hate it for the fact that it turns creepy as a person feels exposed, AI is here to stay. Its penetration in our lives may even continually grow, and maybe we might be soon living in an age where chatbots remind us of our spouse's birthday while we are busy browsing through an ecommerce website. Regardless, AI is continually becoming an empowering tool for digital marketers and works on the tricks to get the information from an individual or the group of people to and make your brand a huge one. It is safe to say that AI is a secured investment, which is sure to get dividends!
Net Solutions is a global digital consultancy that helps brands leverage design, analytics and engineering to create meaningful, personalized customer experiences. Established in the year 2000, we are 230+ people strong, CMMI and ISO 9008 certified company. Our clients include leading brands like Xerox, Microsoft, American Golf, IMG, Mothercare and Euro Car Parts as well as successful startups in UK and around the world. Net Solutions has also been featured in journals of international repute like Wall Street Journal, Economic Times, Hindustan Times, Inc Magazine and Brandon Hall Research.


text:
Pneumonoultramicroscopicsilicovolcanoconiosis ist mit 45 Buchstaben das längste jemals in einem bedeutenden englischen Wörterbuch erschienene Wort. Es bezeichnet auf Deutsch die Quarzstaublunge, in diesem fiktiven Sonderfall durch feine vulkanische Aschen ausgelöst.

Das Wort wurde als Kunstwort 1935 von Everett M. Smith, dem Präsidenten der englischen National Puzzlers' League, bei deren jährlichem Treffen erfunden. Es war eigentlich ein Hoax, der nur als längstes englisches Wort dienen sollte, wurde aber später teils auch von englischen Medizinern als Bezeichnung für die Staublunge verwendet.

Untersuchungen ergaben allerdings, dass vulkanische Aschen anders als andere Silicate kaum ein Risiko für die Bildung einer Silikose oder Pneumokoniose darstellen.

Wortbestandteile
Das Wort setzt sich aus folgenden Bestandteilen zusammen:
 pneumon ist griechisch für Lunge.
 ultramicroscopic, bestehend aus
 ultra ist lateinisch für jenseits. Siehe auch Ultra.
 microscopic ist vom griechischen mikros (klein) und skopein (betrachten) abgeleitet. Siehe auch -skop und Mikroskop.
 silico leitet sich vom lateinischen silex (Kiesel) ab. Siehe auch Sand und Silicium.
 volcano ist lateinisch und leitet sich von Vulcanus ab. Siehe auch Vulkan.
 coniosis leitet sich vom griechischen kónis (Staub) und osis für Krankheit ab.

Weblinks

Einzelnachweise

Sprachlicher Rekord
Krankheitsbild in der Pneumologie
Berufskrankheit

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Your pet may in some situations need to have x-rays taken. Such situations may include fractured bones, arthritis, foreign body ingestion, heart, and lung problems. In such situations x-rays are an important diagnostic tool. The amount of radiation used for this is so low it does not pose a threat to your pet. At Pet Point Animal Hospital we use cutting edge digital x-ray equipment that give a clear image and greatly improve the chance of getting a diagnosis. Our veterinarians will read the images on site and whenever appropriate recommend electronically sending the images out to a radiologist for input from a specialist.


text:
New Ministers Promise Fireworks
State Media
Minister Anxious Masuka
Advocate Fortune Chasi was yesterday fired as Energy and Power Development Minister by President Mnangagwa who replaced him with Muzarabani North legislator Cde Soda Zhemu, while agricultural technocrat Dr Anxious Jongwe Masuka was brought into Cabinet as Lands, Agriculture, Water and Rural Resettlement Minister following the death of Retired Air Chief Marshal Perrance Shiri.
In an interview with state media following his appointment, the incoming Energy and Power Development Minister said he was coming into his new portfolio to play a part in helping Zimbabwe achieve an upper middle income society by 2030.
"I am happy to be given this responsibility by His Excellency the President. The energy sector is expected to play a big role in helping Zimbabwe achieve vision 2030 and I am motivated to help Zimbabwe achieve an upper middle income economy by 2030.
"I have experience in management and this will help me do my duties well in this portfolio, and I am looking forward to having a good working relationship with stakeholders," said Cde Zhemu.
Dr Masuka, seen as an agricultural technocrat with a national and regional reputation, has held several research and management posts, mostly at high level, in his career.
He began in the teaching field as a lecturer at the University of Zimbabwe (UZ) in the Department of Biological Sciences as well as at the Zimbabwe College of Forestry.
He has also worked at the Forestry Commission, the Tobacco Research Board where he rose to general manager, and before his appointment he was the chief executive officer of the Zimbabwe Agricultural Society.
Dr Masuka has cumulatively sat on over 30 boards and associations, and has been involved in consultancy work to projects in the field of agriculture, forestry, environment, public health and rural development in Zimbabwe, in SADC region and beyond.
He is a founding fellow of the Zimbabwe Academy of Sciences in 2004.


Syrian authorities have found a cache of arms and explosives that belonged to a group which recently carried out bomb attacks in the capital Damascus.
The authorites found the stockpile on Wednesday in the village of Khan Al-Shih, 25km south of Damascus.
The Syrian information minister's aide Ahmad al-Haj Ali told Aljazeera the cache contained only light arms.
"The weapons were the kind that can be discreetly collected," he said, adding this suggested that the scale of the attacks in Damascus on Tuesday was less than those witnessed elsewhere in the region.
Earlier, Syrian security forces killed two attackers and wounded two others in a gun battle in Damascus after the group detonated a car bomb in the city's diplomatic quarter.
A Syrian policeman and a woman bystander were also killed in the clash in the suburb of Mazza. An uninhabited building that formerly housed UN offices was damaged in the explosion.
The aide said the attack was meant to send a message that no place was safe these days.
"The attack also indicates that US interests may be targeted anywhere," Ali said.
"I heard two blasts around 15 minutes apart and then security forces came in and there was a firefight," said one local resident.
"We were working in the library and heard lots of gunfire and explosions," said one foreign student close to the scene.
"Everyone was terrified and we ran out of the building to see what was happening."
Syria has seen little violence under the tight security maintained by the government of President Bashar al-Asad after he took over from his father in 2000, although there was fighting between security forces and restive Syrian Kurds last month.


Syria's deputy foreign minister said on Wednesday that the regime has taken "every measure" to respond to any U.S. attack, vowing not to change its position even if a third world war erupts.
In an exclusive interview with AFP, Faisal Muqdad said the government would counter a potential intervention aimed at punishing the regime of Bashar al-Assad over a suspected deadly poison gas strike and was mobilizing its allies.
"The Syrian government will not change position even if there is World War III. No Syrian can sacrifice the independence of his country," he told AFP.
"Syria has taken every measure to retaliate against...an aggression," he added, refusing to provide any clue as to what that might mean.
Muqdad said the regime was mobilizing its allies ahead of a possible strike, as U.S. President Barack Obama lobbies Congress to back intervention and the French parliament debates the issue.
Obama issued a blunt challenge to skeptical U.S. lawmakers on Wednesday to approve his plan for a military strike on Syria, saying otherwise they would put America's international prestige and their own credibility at risk, Reuters reported.
Using a visit to Sweden to build his case for limited military action against Syrian President Assad, Obama insisted that the international community could not remain silent in the face of the "barbarism" of the Aug. 21 chemical weapons attack he blamed on Syrian government forces.
"My credibility is not on the line. The international community's credibility is on the line," Obama told a news conference in Stockholm. "And America and Congress' credibility is on the line, because we give lip service to the notion that these international norms are important," Reuters quoted him as saying.
Just a day before he travels to St. Petersburg to attend a G20 summit hosted by Vladimir Putin, Obama said he held out hope that the Russian president would back away from his support for Assad. But he stopped short of saying he had any high expectations for a change of heart.
Obama's comments came after Putin offered a glimpse of potential international compromise over Syria on Wednesday by declining to entirely rule out Russian backing for military action as he prepared to host a summit of world leaders. At the same time, Putin said any strike on Syria would be illegal without U.N. support.
France, the apparent main ally of the United States in the plan to attack Syria, has warned that not taking action against Assad endangers regional peace and security.
"To not act would be to put in danger peace and security in the entire region. What credibility would our international commitments against non-proliferation of weapons of mass destruction including nuclear weapons stand for?" Prime Minister Jean-Marc Ayrault told a parliamentary debate on Syria.
Buying arms vs. 'selling' the strike: Do Gulf states need more PR on Syria?


Acta Cytol 2019 Apr 12:1-10. Epub 2019 Apr 12.
Department of Medicine, Universidade da Região de Joinville - UNIVILLE, Joinville, Brazil.
Objective: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions.
Acta Cytol 2019 Apr 12:1-12. Epub 2019 Apr 12.
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Acta Cytol 2019 Apr 10:1-21. Epub 2019 Apr 10.
Division of Cytopathology, Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA.
Acta Cytol 2019 Apr 4:1-9. Epub 2019 Apr 4.
AMBIOR, Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.
Acta Cytol 2019 Apr 4:1-12. Epub 2019 Apr 4.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Role of Cytomorphology in the Era of Liquid Biopsy.
Acta Cytol 2019 Apr 3:1-9. Epub 2019 Apr 3.
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
Acta Cytol 2019 Mar 28;63(2):1-12. Epub 2019 Mar 28.
Wolfson Institute of Preventive Medicine, Centre for Cancer Prevention, Queen Mary University of London, Barts and the London School of Medicine, London, United Kingdom.
Acta Cytol 2019 Mar 28:1-9. Epub 2019 Mar 28.
Overview of Molecular Testing of Cytology Specimens.
Acta Cytol 2019 Mar 27:1-11. Epub 2019 Mar 27.
Acta Cytol 2019 Mar 25:1-8. Epub 2019 Mar 25.
Objective: The objective is to study the efficacy of fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) in the diagnosis of lymphoma in a single institution.
Study Design: We retrospectively reviewed 635 FNAB/CNB cases performed in our institution to rule out lymphoma during a 4-year period and collected the relevant clinical and pathological information for statistical analysis.
Acta Cytol 2019 Mar 21:1-7. Epub 2019 Mar 21.
Objectives: The diagnostic performance of cytology in esophageal squamous cell carcinoma (ESCC) is meticulously described.
Fine-Needle Aspiration Biopsy Management of the Axilla in Primary Breast Carcinoma.
Acta Cytol 2019 Mar 20:1-5. Epub 2019 Mar 20.
Pathology Department, St. Vincent's University Hospital, Dublin, Ireland.
Context: Fine-needle aspiration biopsy (FNAB) is frequently used to stage the axilla preoperatively in patients with primary breast carcinoma. In the light of the ACOSOG-Z0011 and AMAROS trials that specified sentinel lymph node biopsy as an inclusion criterion, the role of FNAB in axillary staging is changing.
Role of Ancillary Techniques in Gynecologic Cytopathology Specimens.
Acta Cytol 2019 Mar 19:1-8. Epub 2019 Mar 19.
Acta Cytol 2019 Mar 19:1-7. Epub 2019 Mar 19.
Department of Pathology, Christian Medical College, Vellore, India.
Acta Cytol 2019 Mar 19:1-11. Epub 2019 Mar 19.
Role of Immunocytochemistry in the Cytological Diagnosis of Pulmonary Tumors.
Acta Cytol 2019 Mar 15:1-14. Epub 2019 Mar 15.
HPV Vaccine: Updates and Highlights.
Acta Cytol 2019 Mar 14;63(2):159-168. Epub 2019 Mar 14.
Faculdade de Medicina, Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo (SP), Brazil.
HPV: A Virus-Dinosaur Living among Us?
Acta Cytol 2019 Mar 14;63(2):83-84. Epub 2019 Mar 14.
HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas - Why?
Acta Cytol 2019 Mar 12;63(2):124-142. Epub 2019 Mar 12.
Department of Clinical Research, Biohit Oyj, Helsinki, Finland.
Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982-1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies.
Circulating Tumor DNA: A Step into the Future of Cancer Management.
Acta Cytol 2019 Mar 8:1-10. Epub 2019 Mar 8.
Acta Cytol 2019 Mar 6:1-4. Epub 2019 Mar 6.
The Significance of Circulating Tumour Cells in the Clinic.
Acta Cytol 2019 Feb 28:1-13. Epub 2019 Feb 28.
HPV Infections in Heterosexual Couples: Mechanisms and Covariates of Virus Transmission.
Acta Cytol 2019 Feb 22;63(2):143-147. Epub 2019 Feb 22.
Current Status of p16 Immunohistochemistry and HPV Testing in Fine Needle Aspiration Specimens of the Head and Neck.
Acta Cytol 2019 Feb 15:1-10. Epub 2019 Feb 15.
From HPV Infection to Lesion Progression: The Role of HLA Alleles and Host Immunity.
Acta Cytol 2019 Feb 15;63(2):148-158. Epub 2019 Feb 15.
Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.
Breast Fine Needle Aspiration Biopsy Cytology Using the Newly Proposed IAC Yokohama System for Reporting Breast Cytopathology: The Experience of a Single Institution.
Acta Cytol 2019 Feb 15:1-6. Epub 2019 Feb 15.
Objective: Recently the International Academy of Cytology (IAC) proposed a new reporting system for breast fine needle aspiration biopsy (FNAB) cytology. We aimed to categorize our samples according to this classification and to assess the risk of malignancy (ROM) for each category as well as the diagnostic yield of breast FNAB.
Liquid Biopsy beyond Circulating Tumor Cells and Cell-Free DNA.
Masood's and Modified Masood's Scoring Index: An Evaluation of Fine Needle Aspiration Cytology of Breast Lesions with Histopathological Correlation.
Acta Cytol 2019 Feb 13:1-7. Epub 2019 Feb 13.
Department of Pathology, ESIC Medical College, Faridabad, India.
Circulating Tumour Cells in Predictive Molecular Pathology: Focus on Drug-Sensitive Assays and 3D Culture.
Acta Cytol 2019 Feb 13:1-11. Epub 2019 Feb 13.
Comparison of Conventional Cytology, Liquid-Based Cytology, and Cell Block in the Evaluation of Peritoneal Fluid in Gynecology Malignancies.
Acta Cytol 2019 9;63(1):63-72. Epub 2019 Jan 9.
Background: Peritoneal washing cytology has become an accepted method in evaluating gynecology malignancies.
Objective: The aim of this work was to compare the conventional cytology, liquid-based cytology (LBC), and cell block in the evaluation of peritoneal fluid.
Manufactured Cell Blocks: Turning Smears into Sections.
Acta Cytol 2019 4;63(1):28-34. Epub 2019 Jan 4.
Liquid Biopsy and Lung Cancer.
Acta Cytol 2018 Dec 19:1-8. Epub 2018 Dec 19.
Study of the Pre-Analytical Phase of an ISO 15189: 2012-Certified Cytopathology Laboratory: A 5-Year Institutional Experience.
Acta Cytol 2019 19;63(1):56-62. Epub 2018 Dec 19.
Department of Pathology, Himalayan Institute of Medical Sciences, Swami Rama Himalayan University, Dehradun, India.
Correlation of Ultrasound Findings and Fine-Needle Aspiration Cytology for the Diagnosis of Axillary Lymph Node Metastasis in Patients with Breast Carcinoma.
Acta Cytol 2019 5;63(1):17-22. Epub 2018 Dec 5.
Department of Cytology, Kuwait Cancer Control Center, Safat, Kuwait.
Three-Tiered versus Two-Tiered Classification of Squamous Dysplasia in Cervical Cytology: Results of a Follow-Up Study.
Acta Cytol 2019 5;63(1):44-49. Epub 2018 Dec 5.
Institut für Biometrie und Klinische Epidemiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Objective: Regarding cytological findings of squamous dysplasia, a comparison was made between a three-tiered classification - low-grade squamous intraepithelial lesion (LSIL), high-grade SIL/cervical intraepithelial neoplasia 2 (HSIL/CIN2), and HSIL/CIN3 - and a two-tiered classification - LSIL and HSIL. The respective risk for CIN2+ and CIN3+ was calculated to make decisions regarding management.
BRAF V600 Mutational Status in Melanoma Correlates with Cytologic Features in Fine-Needle Aspirate Specimens.
Acta Cytol 2019 5;63(1):10-16. Epub 2018 Nov 5.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
Diagnostic Accuracy of Fine-Needle Aspiration Cytology for Discrimination of Squamous Cell Carcinoma from Adenocarcinoma in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
Acta Cytol 2018 31;62(5-6):318-326. Epub 2018 Oct 31.
Department of Pathology and ARUP Laboratories, University of Utah, Salt Lake City, Utah, USA.
Objective: To determine the accuracy with which morphology alone can distinguish adenocarcinoma and squamous cell carcinoma in non-small cell lung cancer.
Acta Cytol 2019 31;63(1):1-9. Epub 2018 Oct 31.
The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients' Demographics.
Acta Cytol 2018 31;62(5-6):436-442. Epub 2018 Oct 31.
Division of Cytopathology, Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Background: We report our experience with malignant pleural effusion (MPE) and the impact of patients' demographics on the differential diagnosis at the primary site.


Joey Ciprari presents New England Pride! This movie opened up at If3 in Montreal and also premiered Christmas Eve on Slvsh.com. As a gift for everyone to view! Now because the, "New England Patriot's" are going to the Super Bowl again, I want to share this with the younger ski community! This film is a culmination of my struggles on the urban playing field and the Patriot's through their controversial 2016-2017 season! Go to SLVSH.com for the full interview!


PEER Online, the successor to 'referenced EEG' (or 'rEEG'), has been studied for over 20 years and the evidence supporting the effectiveness of using a physician based outcomes database to guide treatment is significant.
PEER Online is similar to a standard QEEG in that it uses QEEG output variables, but differs from a standard QEEG in that it references the QEEG to a normative and then symptomatic database. By comparing a given patient's QEEG to a database of QEEGs of subjects who have tried and responded to a specific medication, PEER Online can provide useful information regarding the response of neurophysiologically similar patients to a wide number of medications. PEER Online may thus have the advantage of providing physicians with useful information as to medication outcomes before a medication regime is started. As important as the positive findings (e.g. Sensitive finding) from PEER Online may be, physician users have also reported that negative findings (in which neurophysiologically similar patients reported resistant outcomes for certain medications) can be extremely useful in reducing trial and error pharmacotherapy. It has also been used to help select the medication that best matches the QEEG brainwave pattern, regardless of "symptom clusters," currently used for diagnostic nomenclature.
The initial publication of results using the information from an EEG-based database to guide treatment was the Suffin and Emory article in which they examined attentional and affective disorders and their association with pharmacotherapeutic outcomes (Suffin and Emory, 1995). This was a retrospective analysis of treatment outcomes in sequential patients with Attention Deficit Disorder and Affective Disorders. One hundred medication-free patients meeting DSM-III-R criteria for attentional and affective disorders underwent pretreatment QEEG, where the data was submitted to a normative database. Following the EEG, attention-disordered patients were first treated with a stimulant, secondarily with an antidepressant, and tertiarily with an anticonvulsant. Affectively disordered patients were treated initially with antidepressant, and secondarily augmented with anticonvulsant or lithium. Tertiary treatment was a stimulant. Patients were assessed up to 6 months. A Clinical Global Improvement score was assigned. Similar Neurometric subgroups were identified within both the attentional and the affectively disordered patients. Without regard to DSM-III-R diagnosis, there were robust correlations between Neurometric subgroup membership, responsivity to selected pharmacologic agent class(es), and clinical outcome resulting in an 87% response to antidepressants. Another subgroup was 100% responsive to stimulants and a third was 85% responsive to anticonvulsants/lithium. A fourth subgroup was 80% responsive to anticonvulsants. Patients with similar Neurometric features responded to the same class(es) of psychopharmacologic agent(s) despite their DSM-III-R classification.
Other smaller, preliminary studies have suggested a potential role in using this information for medication selection for depression, to name just one psychiatric disorder. A prospective, randomized, controlled 25-week study at a Veterans Affairs hospital consisted of two groups of treatment-resistant depressed patients (n=6 control, n=7 experimental) (Suffin, et al. 2007). The trial used these quantitative EEG features to guide prescribing of psychotropic medications, while the control group received treatment as usual. The results indicated that six of seven subjects augmented with QEEG data received ratings of moderate to marked improvement on both the Ham-D and Beck's Depression Inventory. Only a single subject in the control group did this well. When unblinded, that same subject had been treated successfully with the medication that was consistent with the EEG patterns in the report. Pilot studies using these QEEG variables in eating disorders (Greenblatt, et al. 2011) and substance abuse (Schiller, 2008; Shaffer, et.al. 2005,) demonstrated similar promising results.
Another pilot study (DeBattista, et al. 2008) was conducted to compare this same methodology with the Texas Medication Algorithm Project (TMAP) algorithm for patients with treatment-resistant depression. This 10-week study (n=18) found the data derived from the QEEG variables resulted in statistically greater change from baseline scores for the Quick Inventory of Depressive Symptomatology-Self Report-16 (QIDS-SR16) and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) than TMAP-guided therapy. It also found that five subjects in the TMAP group received a successful TMAP therapy that was identical to what would have been prescribed with the information obtained for the variables from the referenced-EEG database (DeBattista, et al. 2008).
Based on these earlier studies which suggested that using the information from shared outcomes based on QEEG patterns could assist clinicians in being cautious yet efficacious in their choice of medications, especially for treatment-refractory patients, a larger trial was run. In a multicenter, randomized trial, DeBattista found the referenced-EEG database treatment group (experimental) was compared with an optimized treatment based on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study guidelines (control) initially funded by the National Institutes of Health (NIH) in patients with treatment-refractory major depressive disorder (DeBattista, et al. 2011). The experimental group's selection led to statistically better outcomes compared with the control group. The improvement in the group guided by the QEEG data over the control group was significant as early as two weeks and the improvement continued throughout the 12-week study and demonstrated significantly greater improvement on both primary endpoints (QIDS-SR16 and Q-LES-Q-SF, i.e. the same as in the STAR*D study) of P <0.0002 compared with control, as well as statistical superiority in nine of 12 secondary endpoints. Because there are innumerable combinations of therapies available from the databases' report, the DeBattista study was not intended to evaluate any one medication against another, but to examine it as a tool to improve outcomes in this difficult population.
EEG recordings with quantitative analysis yield more information than can be appreciated by simple visual inspection.
Since the 1970's EEG recordings have been digitized and subjected to quantitative analysis (QEEG), which yields more information than can be appreciated by simple visual inspection. QEEG extends EEG technology beyond qualitative identification of abnormality and allows for comparison of an individual patient's EEG pattern with large public databases of age matched, asymptomatic (control) group EEG values (Duffy et al. 1979; John et al., 1977). Medication-induced changes in EEG and QEEG data have been reported for a broad range of antidepressants, benzodiazepines, stimulants, antipsychotics, lithium salts, and anticonvulsants (Herrmann et al., 1979, Itil et al., 1973, 1979; Saletu et al., 1987; Small et al., 1989; Struve, 1987). These drug changes are specific in regard to effects on distinct components of the EEG pattern and are dose-dependent, reversible upon medication withdrawal, and measurable across psychiatric syndromes and in asymptomatic volunteers.
In those studies obtaining baseline, medication-free EEGs, investigators demonstrated unique QEEG features that could be used to aid in treatment guidance. For example, patients with major depressive illness with excess alpha wave magnitudes were retrospectively reported responsive to antidepressants that reduce alpha magnitude (Ohashi, 1994). Similarly, patients with obsessive-compulsive disorder with excess alpha wave activity responded best to antidepressants (Prichep et al., 1993).
In contrast, a subgroup of patients with obsessive-compulsive disorder with elevated theta wave activity did not respond favorably to antidepressants that are known to increase theta wave magnitudes and would therefore be predicted to exacerbate the symptoms of these patients (Prichep et al., 1993). Finally, patients with attention deficit hyperactivity disorder showed a general decrease in EEG patterns and were predicted to respond favorably to methylphenidate, an agent that accelerates EEG frequencies (Satterfield et al., 1973).Subsequent work in depression led to a large multicenter trial (n = 375) (Leuchter et al., 2009) that examined "cordance" – a frontal QEEG index's ability to predict response to the SSRI, escitalopram, after one week of treatment. Subjects were subsequently randomized to remain on treatment or crossed over to alternative treatment. Seventy-five (75) subjects remained on escitalopram and 52% responded to therapy after 49 days. In these subjects, the QEEG pattern indicated response with a 74% accuracy, demonstrating that changes in asymmetry composite EEG index one week into pharmacological treatment can be predictive of positive response to escitalopram at the end of treatment.
These studies found that there were significant EEG heterogeneities within neuropsychiatric disorders. The existence of these subgroups suggests that different patients within the same neuropsychiatric disorder would differentially respond to medications and indicates that EEG patterns could predict the most effective pharmacotherapy for a specific patient.
Without objective physiologically based clinical evidence to support clinical decisions, treating physicians can only respond to their patients in the best way possible, trial and error of approved and un-approved treatments.
Psychiatry is plagued by the lack of a clinically useful biomarker assessment system to guide treatment. Instead, pharmacotherapy is typified by an inductive trial and error process resulting in significant additional morbidity, mortality, and costs due to failed medication trials. Despite extensive research resulting in more than 130 FDA-approved medications used in treating psychiatric disorders, evidence-based guidance is largely lacking for selecting amongst these options to treat refractory patients.
In 2007, the Agency for Healthcare Research and Quality (AHRQ), an agency under the Department of Health and Human Services (DHHS), released a report on a systematic review they conducted on "Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression". In this extensive review of 293 published articles, AHRQ noted almost 40% of patients did not respond to these treatment medications and that over 50% of the patients failed to achieve remission (AHRQ; Effective Health Care #7, Executive Summary, 2007). Although not an impressive response rate, the authors were encouraged by a new study that that was not included in their review due to its late publication; the STAR*D study.
In response to the STAR*D reports showing limited efficacy for a variety of antidepressant strategies, the NIMH funded the recently published CO-MED study (Rush et al., 2011) testing whether starting patients with several antidepressants at the same time would be associated with increased efficacy. Six hundred and sixty-five (665) patients with MDD were randomized to a 12-week acute treatment and participants who experienced substantial benefit in the acute phase were enrolled in an additional 16-week continuation treatment. There was no significant difference between the response or remission rates observed in the three arms in either the acute phase or the continuation phase (12-28 weeks).
Clearly, even in the most optimistic evaluation of available treatments for patients with any treatment resistant disorder, an effective rate of 40% indicates that most medications are simply not sufficiently effective to alleviate the patient's symptoms and most certainly are not providing a remission of disease. This is particularly clear when it is reported that in antidepressant trials there is a placebo response rate of between 35% – 45% (Fava, et al., 2003). Therefore, it can be convincingly argued that these treatments for antidepressants are no more effective than no medication at all.
Recent research raises doubts about the degree to which psychopharmacological treatment has kept pace with our advances in understanding the brain and psychiatric disorders. There is a plethora of new psychiatric medications, but there is growing recognition that these new generation medications may not hold significant advantages over older medications despite their higher costs. It has been observed (DePaulo, 2006) that, when viewed together, the three major studies (STAR*D, CATIE (Stroup, 2003), and STEP-BD (Goldberg, 2009)) question whether or not modern pharmacological provide increased benefits for the additional costs. While none of these studies (STAR*D, CATIE, and STEP-BD) have focused primarily on comparing older and newer treatments, such contrasts do not suggest any dramatic advantages for the newer medications.
When treating patients with mental disorders, particularly patients who are treatment resistant, it's common for patients to stop taking their medications for various reasons, whether it is a lack of effectiveness or side effects of the medication. This lack of adherence to the treatment can collectively be considered tolerability to the treatment, and the evidence for low tolerability of these treatment medications is significant.
With the STAR*D study, over 60% of the patients dropped out of the study prematurely, even though they were provided the free care throughout the study, and were managed at a level far higher than could be expected in the standard care of private practice. Whereas it is difficult to know if they dropped from the study due to the ineffectiveness of the treatment or due to side effects of the medication, there is clear evidence that the side effect profile of these treatments is significant. In the AHRQ systematic review, it was noted that 61% of the patients in the efficacy trials they reviewed had at least 1 adverse event. Further, the same report notes that between 16% and 6% of severe adverse events was reported for the second-generation antidepressants.
In the CO-MED study, although there were no significant differences in efficacy, there was a significant difference in the side effect burden for the patients. In the two polypharmacy arms the maximum side effect burden was between 10% and 15% in both the acute and continuation phases, however in the single treatment arm the side effect burden was only 4% in the acute phase and 5% in the continuation phase. This large, well designed, adequately powered study suggests that for a significant number of patients with MDD, adding medication only adds to their side effects without an increase in efficacy, thus increasing to the low rate of tolerability.
In 2009, Dr. Thomas Insel made similar observations to those of DePaulo, noting that second-generation medications have consistently demonstrated no significant advantage compared with first-generation medication in multiple comparative effectiveness studies funded by the NIMH (Insel, 2009). He also felt that current medication regimes help too few people improve from the perspective of side effects, and a recent prospective study has now even called into question the widely held belief that second-generation antipsychotics produce a lower incidence of tardive dyskinesia (Woods, 2010).
It is increasingly clear that the reason there are so many treatment resistant patients (patients who have failed on two or more medication trials) is due to the lack of effectiveness of the medications and/or the high side effect burden of the treatments. The evidence points to a poor understanding of the underlying physiological causes of the symptoms of these disorders and therefore the ineffective diagnosis as the root cause of the ineffectiveness of the current medication treatments. Without objective physiologically based clinical evidence to support clinical decisions, treating physicians can only respond to their patients in the best way possible, trial and error of approved and un-approved treatments.
Despite the prevalence of mental illness, the treatment of mental illness, and more specifically the most prevalent behavioral disorders of depression, anxiety, bipolar disorder, and , has been problematic.
Mental illness is a profound burden on the world's health and productivity. In fact, it ranks second only to cardiovascular disease in established market economies (Murray & Lopez, 1996). Despite the magnitude of the problem, the treatment of mental illness, and more specifically the most prevalent behavioral disorders of depression, anxiety, bipolar disorder, and ADHD, has been problematic. The reasons are multifaceted; first, there are no objective decision support tools to support treatment. Unlike other areas of medicine, psychiatry has lacked biomarkers that can help guide pharmacotherapy with similar reliability as bacterial assays that guide antibiotic treatment. Second, the treatment guidelines most widely used for behavioral disorders like depression are based upon little or no clinical evidence. (Insel, 2013). And finally, diagnoses for behavioral disorders are based upon symptoms and not the underlying physiological etiology. Psychopharmacotherapy is inductive and assumes that certain behavioral symptoms respond to a specific medication class. This selection process is highly subjective.
As the term implies, with trial and error it is not uncommon for the first, second, or even third treatment medication to not be sufficiently effective to provide significant improvement. Even with multiple medications administered sequentially, many do not respond adequately to pharmacotherapy (Warden et al., 2007). The STAR*D study (Rush et al., 2006), which included more than 4,000 subjects with depression, observed a only a 50% response to the primary medication, and for those patients who failed the primary treatment medication, only an additional response of around 25% was observed when switched either to two other classes of antidepressants or cognitive behavior therapy.
Therefore a significant percentage of patients with non-psychotic behavioral disorders are considered 'Treatment Resistant' (TR). Treatment resistant are those patients that fail to achieve a significant improvement on the initial and/or subsequent treatment regimens. The prevalence of TR patients varies within the different disorders, but published data suggests that for patients with depression up to 50% did not respond to initial treatment. For patients with Bipolar Disorders, 42% of patients failed to achieve recovery (NIHM-funded STEP-BD Best Practice Treatment Pathway (Perlis, 2006)), 10-40% of Anxiety patients do not respond to treatment and many more have residual symptoms (Bystritsky et al., 2006), and for patients with AD/HD, between 30-40% of patients do not respond to repeated trails of medications (Doyle, 2006).
Since the current standard of care for psychiatric patients is trial and error, and because of this process many patients do not find significant improvement to their mental disorders, treating physicians must resort to other methods to find relieve for their patients suffering. More and more, physicians are using multiple medications simultaneously, a practice known as 'Polypharmacy'. In a study undertaken between 1996 and 2005, psychiatrists significantly increased their use of polypharmacy such that outpatient visits resulting in two or more prescribed psychotropic drugs increased from 42.6% in 1996 to 59.8% in 2005 and psychiatric visits resulting in three or more such drugs being prescribed doubled, increasing from 16.9% to 33.2% (Mojtabai et al., 2010).Additionally, physicians are frequently using off label medications to treat treatment resistant patients. Off-label prescribing of psychopharmacology is common and perhaps necessary. Off label uses of psychotropic medications can be part of a good psychopharmacology practice. This is not an unusual practice but he standard of care for psychiatry because of the evidence compared to the unmet needs of patients. The difficulty is that there is little evidence supporting many of the treatments for particular disorders and these medications are powerful psychotropic medications that have a significant side effect profile.
As a result of the trial and error treatment process, patients are prescribed different medications for weeks at a time. The problem, aside from the patient not receiving relief from their disease while trying to find the 'right' treatment, is that the medications being prescribed, both on and off label medications, are powerful drugs that have significant side effect profiles, including the potential increase of suicidality. The side effect burden of these medications can be significant, both medically and economically.
Without objective clinical decision support tools that are based upon evidence, trial and error will continue to be the standard of care for psychiatric medicine. As Thomas Insel, MD, PhD noted in his keynote address to the American Psychiatric Association at their annual meeting in 2005, "We need to develop biomarkers, including brain imaging, to develop the validity of these disorders. We need to develop treatments that go after the core pathology, understood by imaging".
The current model for treating patients is based upon symptom-based medical practice and pathophysiologic measurement. Unfortunately, psychiatry is unique among medical specialties in its lack of such measurements. This has hindered both the advancement of psychiatry in general and clinical practice in particular.
The current medical model for treating patients is based upon symptom-based medical practice and pathophysiologic measurement. Psychiatry is unfortunately unique among medical specialties in its lack of such measurements. This has hindered both the advancement of psychiatry in general and clinical practice in particular. Thus, in the current therapeutic model for psychiatry, and in particular of any treatment resistant disorder, psychiatrists much choose treatment medications based upon patient symptoms, response to previous treatment, and behaviors. Significant limitations result because these illness features do not have a simple relationship with medication response. Without a defined pathologic abnormality to treat, or a physiologic marker to guide treatment, psychiatrists have been forced into the position of choosing between large numbers of psychotropic medications without ample evidence to support their choices.
This is particularly true for Major Depressive Disorder (MDD), and specifically for Treatment Resistant Depression (TRD). Whereas the same holds true for bipolar disorders and other psychotic disorders, MDD is very representative of the issues.
These guidelines and reports attempt to provide insight regarding the treatment of depression from the first line therapy through more complex scenarios involving TRD.
The APA guidelines document is a practical guide to the management of major depressive disorder for adults over the age of 18 and represents a synthesis of current scientific knowledge and rational clinical practice. This guideline strives to be as free as possible of bias toward a theoretical posture, and it aims to represent a practical approach to treatment.
The TMAP is a treatment algorithm that constitutes the most extensive and comprehensive development and implementation to date of medication algorithms for persons with serious mental illness. An algorithm is a rule or set of rules that is applied to solving a problem. Medication algorithms are a subset of practice guidelines. They are distinguished by an exclusive focus on medications and by a more step-by-step approach to clinical decisions. Current projects address the treatment of Schizophrenia, bipolar disorder, and major depression. TMAP was initiated by the Texas Department of Mental Health and Mental Retardation in collaboration with a consortium of Texas academic medical centers. The development of the TMAP algorithms incorporated expert panels, literature review, and consensus conferences. The Texas Implementation of Medication Algorithms (TIMA) is the practical, clinician-targeted implementation of TMAP.
STAR*D was set up to evaluate clinical strategies to improve outcomes for patients with TRD, determine the best next-step treatments for depressed patients who do not respond satisfactorily to earlier treatment attempts, and compare relative efficacy and patients' acceptance of different treatment strategies to relieve depression. Focusing on the common clinical question of what to do next when patients fail to respond to a standard trial of treatment with antidepressant medication, STAR*D aimed a defining which subsequent treatment strategies, in what order or sequence, and in what combination(s) are both acceptable to patients and provide the best clinical results with the least side effects.
Operationally, those who did not respond to a line of treatment were then assigned to either a) augmenting the first antidepressant with other medications or psychotherapy, b) changing to a different antidepressant or psychotherapy, c) adding psychotherapy or discontinuing the first antidepressant medication while switching to psychotherapy, d) switching to another antidepressant, e) augmenting the first antidepressant with other medications, or f) augmenting first antidepressant with other medications or switching to another antidepressant. So after failing the first line of therapy, patients were randomized to the next-step (Level 2) treatment strategies based upon the above options. After indicating which options are or are not acceptable to them, patients will be randomly assigned to a treatment option within those strategies that are deemed acceptable to and medically safe for them. Patients who did not have a satisfactory therapeutic response to their Level 2 treatment were presented with additional treatment options as a third step (Level 3). Again, they were assigned randomly to one option, which included medication switching and medication augmentation, at Level 3 of the treatment protocol. Similarly, Level 4 treatment options were provided for patients who did not respond satisfactorily to the Level 3 of the treatment protocol. STAR*D reported Level 3 and Level 4 results in three trials; two trials for Level 3 and one trial for Level 4(Fava, 2006; McGrath, 2006; Nierenberg, 2006; Rush 2006). Level 3 and Level 4 randomized controlled trials in STAR*D referred to trials in patients who had previously failed two and three antidepressant medication trials, respectively.
Whereas all of these guidelines are valuable, all are problematic. While the APA guidelines provide evidence support for their first line treatment recommendations, no evidence is provided for the TRD treatment recommendations and did not reference any studies specifically evaluating TRD. TMAP was primarily designed using expert panel consensus, which is considered a lower level of evidence (Level 4) on the scale of evidence used by the Centre for Evidence Based Medicine (CEBM). The remission rates in STAR*D using Hamilton-D scores in all treatment arms in the three trials ranged between 6.9% – 24.7%. These rates are relatively low as response rates in excess of 20% are often observed in placebo control treatment arms (Maes, 1996). This implies that the results for STAR*D trials for Level 3 and Level 4 can be considered negative trials.
Other independent analyses of STAR*D have highlighted the disappointing outcomes from the study, particularly its low level of sustained improvement during the follow-up (Fava, 2007; Ghaemi, 2008; Pigott, 2010; Pigott, 2011). Unfortunately, the overly favorable interpretations of the results of STAR*D (Gaynes, 2008) have fostered further trial and error, frequently with no solid clinical or scientific rationale.
Rush, A., Trivedi, M., Wisniewski, S., et al. Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A Star*D Report. American Journal of Psychiatry 2006; 163:1905-1917.
Although the practice of polypharmacy is growing and being institutionalized by the National Committee for Quality Assurance (NCQA) and virtually mandated by the Affordable Care Act of 2010, there's a growing number of reports and meta-analyses that the practice of polypharmacy is lacking solid evidence of effectiveness, and worse, an increasing side effect burden that would off-set any benefit.
Although different authors have defined polypharmacy with different meaning, most often, the definition of polypharmacy is made with regard to the specific number of medication prescribed, and most commonly, it is the use of two or more medications to treat the same condition.
There has been a rapid increase in the use of polypharmacy in psychiatry. The reasons may be multifactorial, such as an increasing number of available medications targeting new and different symptoms and receptors, or even the pressure on psychiatrists to focus on medication treatment. Regardless of the reasons, the trend is clear, with psychiatrists now frequently seeing patients presenting on multiple psychiatric medications (Hoffman, 2011).
Polypharmacy of difficult psychiatric patients is rapidly becoming the norm. In a study undertaken between 1996 and 2005, psychiatrists significantly increased their use of polypharmacy such that outpatients visits resulting in two or more prescribed psychotropic drugs increased from 42.6% in 1996 to 59.8% in 2005 and psychiatric visits resulting in three or more such drugs being prescribed almost doubled, increasing from 17% to 33% (Mojtabai, 2010).
The rationale for polypharmacy or augmentation strategies to enhance retention or to increase remission rates is supported by findings from empirical research. As noted by Yury et al., 2009, most patients with unipolar depression do not remit with initial antidepressant monotherapy; second, no monotherapy medication is robustly different from others in achieving remission; third, the lack of response with antidepressant monotherapy leads to high dropout rates among depressed patients; and fourth, the emergence of adverse side effects (e.g., agitation, insomnia) or persistence of some initial baseline symptoms (e.g., anxiety, insomnia) may lead to premature discontinuation from monotherapy.
Yury went on to note that there are significant limitations to the American Psychiatric Association (APA) guidelines to the use of augmentation to treat depression. "First, researchers have noted a lack of data to inform the sequence in which augmentation strategies should be implemented or for identifying the types of patients for whom specific strategies might be most helpful (Fava et al., 2003;). Further, it appears that the majority of medications suggested as augmenting agents have no studies, or few examining them as augmenting agents (Thase, 2001). Thus, it is an irony of current psychiatric practice that the most common augmentation strategies for the treatment of depression may be those with the least evidence of efficacy (Thase, 2004)." As emphasized in Pigott et al., 2010, the APA's continuation phase guideline is profoundly misguided because there is no apparent benefit for most patients from continued antidepressant drug treatment, yet this practice unnecessarily exposes such patients to significant risks.
The STAR*D study was a large trail that included some augmentations. In the trial, patients who failed to respond to the step-1 medication and agreed to be randomized to augmentation strategies received either 12 weeks of a step-2 medication added to their step-1 medication. Such augmentation resulted in a 39% remission rate, but with a subsequent relapse of up to 67%. Subsequent augmentation had even lower remission and higher relapse rates. As noted by Yury et al., "one might consider the results to be disappointing and reflect and unfavorable risk-benefit ratio given that about 4% of the patients experienced a serious adverse event from the first augmentation and that about 13% had to discontinue the study because of intolerance of side effects" (Yury, 2009). Even more concerning is that the STAR*D study found that 8.6% of step-1 patients reported an increase in suicide ideation during the acute phase treatment (Perlis, 2007) and in another report (Nierenberg, 2010) 71.3 % who had a remission during the acute-care treatment reported increased weight gain and 71.7% reported residual symptoms of sleep disturbance despite having received remission (Pigott, 2011).
Although the practice of polypharmacy is growing and being institutionalized by the National Committee for Quality Assurance (NCQA) and virtually mandated by the Affordable Care Act of 2010, there is a growing number of reports and meta-analyses that the practice of polypharmacy is lacking solid evidence of effectiveness, and worse, an increase side effect burden that would off-set any benefit. Both Hoffman and Pigott have recently noted that patients either wash out or off medication may achieve similar benefit to those of polypharmacy (Hoffman, 2011; Pigott, 2011).


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The number of people diagnosed with ADHD continues to skyrocket. It can't be explained on the basis of genetics or biology. Rather it seems this increase in diagnosis is simply the result of Big Pharma working with doctors, scientists, educators, parents, government, celebrities, and the media. That is, it's the result of marketing. I (K.W.) don't know about you, but it seems everywhere I turn there's a new "discovery" about the prevalence or consequences of ADHD.
Late last year, The New York Times took an in-depth look at the industry fueling the huge rise in ADHD prescriptions, exploring how marketing turned a once-obscure disorder into a $9 billion business. In his investigative article, "The Selling of Attention Deficit Disorder", reporter Alan Schwarz explored the formula that the advertising/marketing industry used to push these conditions and treatments. It required that both drug makers and doctors insist that ADHD is being under-diagnosed in children, and that if inadequate (medication) treatment persists the condition will result in much bigger problems when affected children become adults. Thus the industry ensures customers for life.
I know when I was a kid growing up in the 70s and 80s, this ADHD diagnosis didn't really exist. Yet, now, my cohort is the exact population being targeted with the industry propaganda both about our children — and ourselves. With the children's market booming, the industry is shifting its focus to undiagnosed adult ADHD. Its messaging implies that adult ADHD can limit professional success, strain relationships (often ending in divorce), and diminish overall well-being. Insofar as adults far outnumber children, this market represents a huge growth opportunity. In fact, the latest edition of the DSM-V is the first to explicitly recognize adult ADHD. This will no doubt help fuel the fastest-growing segment of the market — adults who were never diagnosed as children.
Big Pharma uses celebrities like Maroon 5's Adam Levine to talk about their experience with ADHD and then drives normal people on-line to take a quiz to see if they may have ADHD symptoms. I took this quick 6 question questionnaire and scored 20 which told me that ADHD may be likely and that I should visit with my healthcare professional who can make the diagnosis.
Yes, I have sometimes have trouble concentrating, forgetting things, or being motivated to start or complete projects. But I find it hard to believe that this means I am at high risk for adult ADHD. Without any no blood test or other sort of biological marker, I wonder how my doctor would diagnose me with ADHD. I worry that she might use this kind of quiz.
The selling of sickness is more prevalent than people realize. The public has become convinced that every life distress should be medically diagnosed and treated. Having difficulty concentrating or having trouble completing projects is hardly a medical condition. We must resist the temptations of the healthcare marketing/advertising industry to oversimplify, overmedicalize and overtreat.


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Best Cheap Summer Vacations
Thanks to balmy temperatures, long days and school recess, summer is a popular time to take a vacation. Unfortunately, it can also be one of the most expensive times to travel, making it difficult to find a budget-friendly destination. To help you in your search, U.S. News considered affordability and traveler appeal to determine the best cheap summer vacations. Vote for your favorite destination below to help determine next year's ranking.
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The Finger Lakes
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Roaming buffaloes, majestic mountains and breathtaking geysers all populate Yellowstone's more than 2,220,000 acres of wilderness. Travelers searching for an affordable vacation that doesn't skimp on memorable moments will likely appreciate several cost-effective aspects of this national park. Entrance fees cost $35 per vehicle or $20 per person on foot for seven days, while campsites start at $15 per night. Once you've settled in, explore the park's incredible hiking trails, which wind from colorful thermal basins to large lakes.
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Bar Harbor, Maine, is basically a postcard that has found its way into the real world. Acadia National Park flanks the town on one side and Frenchman Bay on the other, so it has an abundance of options for both outdoor enthusiasts and water sports fans. Summer is the best time to visit because the weather is warm and dry. Plus, this season is when the town offers a variety of free activities, including outdoor movies at Agamont Park and tastings and tours of local breweries.
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Moab, Utah, is unique in that it borders two of the state's national parks. Arches National Park (to the north) is where visitors can marvel at precarious looking sandstone monuments like the famous Delicate Arch. Meanwhile, Canyonlands National Park (which sits southwest of town) offers stunning views of Utah's expansive desert landscapes. In and around Moab, travelers will find an array of affordable accommodations, ranging from campgrounds to motels to vacation rentals. All of this makes Moab a budget-friendly destination for nature lovers.
It doesn't get more affordable than camping, and this UNESCO World Heritage Site is a unique place to rough it. You'll have to contend with crowds along the South Rim, but the photo possibilities will be well worth the cramped quarters. Campsites are just $18 per night during the warmer months, while the entrance fee for vehicles is $35 and lasts seven days. Pack your own food to save even more.
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If you avoid the area's casinos, you'll find that Niagara Falls is an exceptionally affordable summer vacation destination. To save money, consider purchasing one of the area's bundled passes, which may include admission to activities like a guided Journey Behind the Falls tour and a Hornblower Niagara Cruises boat ride. Summer may be the peak season, but booking in advance helps cut costs. Plus, nothing beats basking in Niagara Falls' mist on 80-degree days.
If you're seeking a serious dose of history, Williamsburg, Virginia, may be the right vacation spot for you. Step back in time at Colonial Williamsburg, visit the site of the first settlement at Jamestown and wander around the Yorktown Battlefield. Should you want to check out pricier attractions like Water Country USA and Busch Gardens, opt for a summer combo ticket that covers unlimited access to these locations and Colonial Williamsburg for seven days. Because of Williamsburg's location, East Coast-based travelers can easily reach all of these hot spots.
Nicknamed "The Family Beach," Surfside Beach is a 2-mile strip on the South Carolina coast. Visitors can look forward to games, fishing and a summer concert series during the warmer months. Surfside also features an assortment of youth attractions designed with accessibility in mind. What's more, the city's free beaches and pier (which are easy to reach via a cheap summer shuttle) are exceptionally maintained, guaranteeing summer travelers a clean and safe getaway.
If you can stand the scorching temps, Albuquerque, New Mexico, will reward you with a variety of travel deals in the summer. Immerse yourself in Native American culture at places like the historic Old Town district and the Indian Pueblo Cultural Center. Then, take in incredible views from the Sandia Peak Tramway, the longest aerial tram in the United States. For the best rates, avoid visiting during one of the city's numerous summer festivals.
The capital of Maryland, Annapolis is a great summer destination for history buffs. The city played a pivotal role in the Civil War and the War of 1812. Today, it's home to the United States Naval Academy, which houses a museum and beautiful grounds. When travelers are not learning about the city's storied past, they can go sailing on the Chesapeake Bay or enjoy a meal at one of the many seafood restaurants.
#10 in Best Cheap Summer Vacations
This city on Florida's west coast offers an assortment of cheap summer activities and attractions to please every type of traveler. When you're not soaking up some sun on nearby beaches, spot local flora and fauna at places like Manatee Park and the J.N. "Ding" Darling National Wildlife Refuge. Or, indulge in a history lesson at the winter estates of Henry Ford and Thomas Edison. Since summer is a popular time to visit Fort Myers, reserve your accommodations months in advance to secure lower rates.
Sitting on the Ontario-Quebec border, Ottawa serves as Canada's capital, as well as an excellent destination for culture enthusiasts. Visitors can explore historic geographic attractions, such as the Rideau Canal and the neo-Gothic structures of Parliament Hill. Instead of eating out, book a hotel room or vacation rental with a kitchen and plan on cooking your own meals using ingredients (and anything else you could want) purchased at the venerable ByWard Market.
Like the Caribbean, Fort Lauderdale, Florida, sees the most visitors during the winter and spring, meaning you can snag cheaper flights and hotel rates if you plan a summer trip. The smaller crowds also guarantee that there will be more beachfront up for grabs, so you won't have to fight for a prime location. Plus, it's only roughly 30 miles north of Miami, so spending an afternoon on Miami Beach doesn't leave you stuck paying for an expensive Miami hotel.
As a desert city in Arizona, Tucson feels especially warm during the summer, so it is imperative that you remember to bring a water bottle everywhere you go. This historic town does not disappoint its tourists, though, offering scenic drives, hiking trails, guided bike tours and more. When you need a break from the Arizona sun, head indoors to explore free or cheap attractions like Mission San Xavier del Bac and the Franklin Auto Museum.
The typically expensive Boca Raton, Florida, sees its lowest hotel prices of the year come summertime. What's more, many of the city's resident snowbirds have flown the coop for the season, so crowds are virtually nonexistent. Plus, many of Boca's attractions – such as Mizner Park, the Gumbo Limbo Nature Center and Sugar Sand Park – are free to enjoy. Keep in mind that hurricane season runs from June through November, so booking nonrefundable rooms during late summer could come back to bite you.
The Finger Lakes' abundance of affordable activities and attractions helps it stand out from similarly impressive bodies of water. Boating, fishing, swimming and water sports can be done on the area's namesake lakes, while hiking paths weave through the scenic spots between the lakes. Should visitors desire a break from the outdoors, they can head to air-conditioned museums like the George Eastman Museum and The Strong National Museum of Play. To keep trip costs down, visit the Finger Lakes Tourism Alliance's website for coupons and vacation packages.
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Bogdan: I can be Liverpool FC's number one
Hungarian keeper out to impress on his debut against Carlisle
Adam Bogdan of Liverpool during the international friendly match between Malaysia XI and Liverpool FC at Bukit Jalil National Stadium on July 24, 2015 in Kuala Lumpur, Malaysia. (Photo by Andrew Powell/Liverpool FC via Getty Images)
Adam Bogdan has set his sights on becoming Liverpool's No 1 as he insisted: "I didn't come here to sit on the bench."
The Hungary international goalkeeper will make his debut for the Reds in Wednesday night's third round Capital One Cup tie with Carlisle United at Anfield.
Bogdan signed for Liverpool from Bolton on a free transfer this summer having been lined up a replacement for Brad Jones, who was released once his contract expired.
The 27-year-old knew he would start the season as back-up to Simon Mignolet but he's determined to prove he can establish himself as the first-choice shot-stopper at Anfield.
"The team hasn't been announced yet but if I get the chance to start then it will be a big night for me," Bogdan told the ECHO.
"If I play then it's a chance to get a game under my belt and show what I can do.
Adam Bogdan signs in at Liverpool
"That's what we're all here for - to enjoy playing for Liverpool.
"I didn't sign for Liverpool to sit around on the bench or be happy being the No 2 keeper.
"Like everyone else, I'm here to compete for a place in the team."
Cup game at Anfield was one of my best performances
Bogdan is no stranger to excelling at Anfield. He was Bolton's hero back in January when he pulled off a string of fine saves in a goalless FA Cup fourth round tie against Liverpool.
That display helped to convince Brendan Rodgers that Bogdan was the answer when the Reds boss was in the market for a keeper.
"It was a good day for Bolton and for myself," Bogdan recalled.
Adam Bogdan makes a save during Bolton's FA Cup tie at Anfield
"It was certainly one of my best performances. Liverpool created a lot of chances but I kept a clean sheet and it will always be a good memory for me.
"That was the first time I'd ever played at Anfield. I'd sat on the bench there before.
"The atmosphere was great and it was amazing being out on that pitch and hearing You'll Never Walk Alone.
I can't wait to run towards the Kop
"I remember the applause from the Kop when I ran towards them and thinking 'do I clap back or not?'
"I didn't know beforehand that the Kop do that for away keepers.
"Now I can't wait to experience that as a Liverpool player.
"There will be some nerves, there are before every game, but once the game starts I'll be fully concentrated and focused on my job."
Liverpool's Raheem Sterling in action with Bolton's Adam Bogdan
Bogdan arrived with a wealth of experience having spent eight years at Bolton following his move from Vasas in his home city of Budapest.
He's enjoying being put through his paces by Liverpool goalkeeping coach John Achterberg.
"I've settled in well. All the lads have been great and all the staff have made me feel very welcome," he said.
"It took a couple of weeks for me to pick up the tempo of the training and the different ways but I'm really happy.
Brad Jones, Simon MIgnolet, John Achterberg and Danny Ward of at Melwood Training Ground on March 6, 2015 (Photo by Andrew Powell/Liverpool FC via Getty Images)
"John is a guy who likes to think a lot and he's a fantastic coach. He analyses everything – your decision making and your positioning.
"That's what you need in order to be a top keeper. He has a real eye for detail.
"We train hard, not only out on the pitches, but also in the gym and with analysing footage.
"In the Premier League, the margins are very small so you need the best preparation possible. He keeps you on your toes and says what you need to improve."
I like working with Simon and I'm learning every day
Bogdan may have designs on Mignolet's shirt but the Hungarian has huge respect for the Belgian, who has entered his third season with the Reds.
"Of course when I signed I knew it was going to be hard with Simon for competition," he said.
"Since I signed, I've seen every day in training how much effort and energy he puts in to get better and to stay as the No 1.
"I like working with him and I'm learning every day in a fantastic environment."
Simon Mignolet of Liverpool makes a save during the Barclays Premier League match between Liverpool and Norwich City on September 20, 2015 in Liverpool, United Kingdom. (Photo by Andrew Powell/Liverpool FC via Getty Images)
Mignolet came in for plenty of stick after his weak punch from a corner led to Russell Martin rescuing a point for Norwich at Anfield last weekend. But Bogdan insists much of the criticism was unfair.
"If he had not come for the ball then it would have been a free header," he said.
"It wasn't easy because the corner was fantastic – very low and fast.
"He managed to get in front of their player to punch the ball and it was just unlucky that it dropped to Martin who finished like he did.
"After that we could have been 2-1 down but Simon made a fantastic save to keep us in the game.
This competition gives chances for those players not involved in the league
"We had many chances after that and could have won the game 3-1 or 4-1. If we had then no-one would have talked about the goal we conceded."
"In the Premier League everything happens so quickly. The margins are so small and you need luck as well."
It was the League Cup which launched Bogdan's career in England. He made his Bolton debut in a 1-0 win away to Southampton just over five years ago.
Adam Bogdan of Liverpool during a Training session at Saujana Resort on July 22, 2015 in Kuala Lumpur, Malaysia. (Photo by Andrew Powell/Liverpool FC via Getty Images)
Now he hopes the visit of League Two outfit Carlisle marks the start of a bright new chapter for him.
"A competition like this gives chances to those players who haven't been involved much in the league games," he said.
"That what happened for me at Bolton and then you need to show your qualities.
"It's an important competition both for myself and also for the club. Liverpool has a big history in the League Cup and we want to do well in it this season.
"It's not going to be easy. It's a massive occasion for Carlisle.
"They will lift their game and play with freedom because no-one expects them to win.
"We have to all focus on doing our jobs right. We have to match them for effort and commitment. If we do that then we'll be able to go through."
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Did you know you can track whether your contacts are following through with their commitment to call from the Request a Call goal type?
This is a setting found in the Organization level Advanced settings and can be adjusted by Org- and Account-level Admins.
Once your goal is created, your organizers can start texting. Each contact will be sent a unique tracking number that let's you see if they've clicked the number they were texted and called their Targeted Contact Phone Number!
On your goals page for your group you'll see how many people said they will contact, how many said they won't, and the number that were actually contacted within the goal timeframe.
Any contact that made the phone call will be removed from your reminders list, so you won't bother people who made phone calls.
NOTE: Call tracking cannot be disabled for an active Goal already in progress. Any Goals created while phone tracking is enabled will continue for the duration of the Goal. Once call tracking is disabled any new Goals created will be created without call tracking.