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Android News / All News / Moto E4 Plus Shells Hint At The Phone's Three Color Options
Moto E4 Plus Shells Hint At The Phone's Three Color Options
By Justin Diaz
A set of leaked images for Moto E4 Plus shells hint at the phone's three color options. The leaked images of the cases for one of Motorola and Lenvo's upcoming smartphones come in gold, dark grey, and blue color options which suggests that these may be the colors that the companies have chosen for the Moto E4 Plus, and if that's the case it could be the same three colors for the Moto E4 as well.
The design of the shells seem to match the design and shape of the Moto E4 Plus, and they feature compatible cutouts for the camera on the back of the phone as well as buttons for the power and volume on the right side of the phone, which helps to point to the possibility that these are indeed meant for the Moto E4 Plus. One thing to consider is that renders of both the Gold and dark grey models have already surfaced which lends more credence to a potential third color choice for consumers, this being the blue color that could match the color of the shell in the image above.
Another thing to consider is that the previously leaked render of the Moto E4 Plus shows as more of a dark grey whereas the leaked image of the shell for the case that has surfaced today looks like more of a black color, so it's entirely possible that the Moto E4 Plus will launch in a black color as well, or just that the case is darker than the actual color of the phone. Either way, there seems to be at least three colors of the upcoming device and that gives consumers more choice which is always a good thing when it comes to buying devices. Whatever colors the phone does launch in may be revealed soon enough, as it's been rumored that Lenovo and Motorola will be announcing some new devices in the very near future. According to some of the most recent rumors, the two companies may end up unveiling the Moto Z2 series of devices as well as the Moto E4 and Moto E4 Plus sometime this month, though it's also worth noting that it has also been rumored the Moto E4 Plus will launch on July 17th.
Moto E4 Plus Shell Color Leaks 2
Justin Diaz
Justin has written for Android Headlines since 2012 and currently adopts a Editor role with a specific focus on mobile gaming and game-streaming services. Prior to the move to Android Headlines Justin spent almost eight years working directly within the wireless industry. Contact him at [email protected]


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Q: How to disable account expiration and mandatory change of password after it expires in linux? I want to change the password expiration to non expire and for that i used below command
[root@test-host ~]# chage -l test
Last password change                                    : password must be changed
Password expires                                        : password must be changed
Password inactive                                       : password must be changed
Account expires                                         : never
Minimum number of days between password change          : 0

chage -m 0 -M 99999 -I -1 -E -1 test

[root@test-host ~]# chage -l test
Last password change                                    : Jun 10, 2017
Password expires                                        : never
Password inactive                                       : never
Account expires                                         : never
Minimum number of days between password change          : 0
Maximum number of days between password change          : 99999
Number of days of warning before password expires       : 7

But eventhough it is now in non expire status, it is asking me to change the password.So is it anyway to disable change of existing password after expire
test@test-host's password:
You are required to change your password immediately (root enforced)
Last login: Wed Jun 14 01:28:07 2017 from
WARNING: Your password has expired.
You must change your password now and login again!
Changing password for user test.
Changing password for test.

A: Have you tried:
passwd -x -1 -n -1 -w -1 ${USER}
It may produce the same result but it could do the trick.

redpajama_set_name: RedPajamaStackExchange


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Home » Awareness » Spending time outdoors reduces the risk of 6 different ailments
Spending time outdoors reduces the risk of 6 different ailments
Posted on 11th September 2018 by Don in Awareness
Traveler girl walking through fields. Young girl traveler walking in nature. Traveler with backpack in nature. Girl traveler walk through nature in summer day. Traveler. Summer. Backpack. Girl. Walk. Nature
Living close to nature and spending time outside has significant and wide-ranging health benefits — according to new research from the University of East Anglia. 'The health benefits of the great outdoors: A systematic review and meta-analysis of green space exposure and health outcomes' is published in the journal Environmental Research.
"Nature is fuel for the soul," says Richard Ryan, lead author and a professor of psychology at the University of Rochester. "Often when we feel depleted we reach for a cup of coffee, but research suggests a better way to get energized is to connect with nature," he says.
It's an essential component for good health, according to University of Illinois environment and behavior researcher Frances "Ming" Kuo.
The health benefits of green spaces have demanded the attention of policymakers since the 1800s. Although much evidence suggests greenspace exposure is beneficial for health, there exists no systematic review and meta-analysis to synthesize and quantify the impact of green space on a wide range of health outcomes.
A new report published today reveals that exposure to green space reduces the risk of type II diabetes, cardiovascular disease, premature death, preterm birth, stress, and high blood pressure.
Populations with higher levels of green space exposure are also more likely to report good overall health — according to global data involving more than 290 million people.
Grounding — a simple, pleasurable way to reduce inflammation and chronic disease
Lead author Caoimhe Twohig-Bennett, from UEA's Norwich Medical School, said: "Spending time in nature certainly makes us feel healthier, but until now the impact on our long-term wellbeing hasn't been fully understood.
"We gathered evidence from over 140 studies involving more than 290 million people to see whether nature really does provide a health boost."
The research team studied data from 20 countries including the UK, the US, Spain, France, Germany, Australia and Japan — where Shinrin Yoku or 'forest bathing' is already a popular practice.
'Green space' was defined as open, undeveloped land with natural vegetation as well as urban green spaces, which included urban parks and street greenery.
The team analyzed how the health of people with little access to green spaces compared to that of people with the highest amounts of exposure.
"We found that spending time in, or living close to, natural green spaces is associated with diverse and significant health benefits. It reduces the risk of type II diabetes, cardiovascular disease, premature death, and preterm birth, and increases sleep duration.
"People living closer to nature also had reduced diastolic blood pressure, heart rate and stress. In fact, one of the really interesting things we found is that exposure to greenspace significantly reduces people's levels of salivary cortisol — a physiological marker of stress.
"This is really important because in the UK, 11.7 million working days are lost annually due to stress, depression or anxiety."
"Forest bathing is already really popular as a therapy in Japan — with participants spending time in the forest either sitting or lying down, or just walking around. Our study shows that perhaps they have the right idea!
1982 Japanese bathing practice decreases anxiety and blood pressure
"Although we have looked at a large body of research on the relationship between greenspace and health, we don't know exactly what it is that causes this relationship.
"People living near greenspace likely have more opportunities for physical activity and socialising. Meanwhile, exposure to a diverse variety of bacteria present in natural areas may also have benefits for the immune system and reduce inflammation.
"Much of the research from Japan suggests that phytoncides — organic compounds with antibacterial properties — released by trees could explain the health-boosting properties of forest bathing."
Study co-author Prof Andy Jones, also from UEA, said: "We often reach for medication when we're unwell but exposure to health-promoting environments is increasingly recognised as both preventing and helping treat disease. Our study shows that the size of these benefits can be enough to have a meaningful clinical impact."
Grounding: The missing element to healing autoimmunity?
The research team hope that their findings will prompt doctors and other healthcare professionals to recommend that patients spend more time in greenspace and natural areas.
Twohig-Bennett said: "We hope that this research will inspire people to get outside more and feel the health benefits for themselves. Hopefully our results will encourage policymakers and town planners to invest in the creation, regeneration, and maintenance of parks and greenspaces, particularly in urban residential areas and deprived communities that could benefit the most."
*Article originally appeared at Prevent Disease.
Source: https://www.healthnutnews.com/spending-time-outdoors-reduces-the-risk-of-6-different-ailments/

redpajama_set_name: RedPajamaCommonCrawl


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Q: SELECT query String contains '%' character The requirement is to query for all the strings which contains '%' character in it. Example : "John%", "Jac%ob"
As '%' itself is a wildcard character, How to query for this??
Thanks in advance!

A: When using LIKE with wildcards such as % you can escape the wildcard character with a \
SELECT *
FROM yourtable
WHERE yourstring LIKE '%John\%%' ESCAPE '\';

Or:
SELECT *
FROM yourtable
WHERE yourstring LIKE '%Jac\%ob%' ESCAPE '\';

Also notice that they use single quotes for containing the strings, rather than double quotes.
Thanks to ZLK and blendenzo for clarification in the comments below.


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New tool exposes self-edits in Wikipedia
A new tool can help trace anonymous Wikipedia edits -- and improve the reliability of the online encyclopedia.
John Blau (IDG News Service) 16 August, 2007 13:29
A word of caution about editing entries "anonymously" in Wikipedia: a tool has been developed that can show who made the changes.
Virgil Griffith, who will be a graduate student at the California Institute of Technology starting in September, has developed Wikipedia Scanner, a search tool that traces the IP (Internet Protocol) address of people who make edits to the online encyclopedia.
While Wikipedia allows anyone to make edits, it keeps detailed logs of the changes made. And although people can make changes without identifying themselves, the changes often create digital fingerprints that provide information about the user, such as the location of the computer used to make the edit.
Many of the edits detected by the scanner correct spelling mistakes or obvious factual errors, but others have been used to polish entries by rewriting or removing critical material. The scanner has traced entries to people at several large companies who appear to have altered potentially damaging content.
Someone on Wal-Mart Stores Inc.'s network, for instance, altered a line about the wages it pays employees. The original entry stated that "Wages at Wal-Mart are about 20% less than at other retail stores," citing the author Greg Palast as the source. The revised entry reads: "The average wage at Wal-Mart is almost double the federal minimum wage," and changes the attribution to Wal-Mart.
A person with access to an IP address at the election systems division of Diebold Inc. cut large sections out of an entry about concerns of security experts over the integrity of Diebold's voting machines, as well as information about the its CEO's fund raising for President George W. Bush. The deleted text was later restored.
And a user of a computer at the British Broadcasting Corp. changed Bush's middle name from "Walker" to "Wanker."
The scanner has also tracked digital fingerprints that have led to computers at the Central Intelligence Agency and the Vatican.
Griffith created the tool to "create minor public relations disasters for companies and organizations I dislike," he wrote on his Web site. He admitted that it's impossible to be sure if the edits were made by someone working at one of the organizations, although the IP address reveals that they were made by someone with access to their network, he says.
"If the edit occurred during working hours, then we can reasonably assume that the person is either an agent of that company or a guest that was allowed access to their network," he wrote.
Griffith came up with the idea when he "heard about Congressmen being caught for white-washing their wikipedia pages," he said.
He said he believes that anonymous speech is important for open projects like Wikipedia. The online encyclopedia works fine today for "noncontroversial topics," he said, but tools like Wikipedia Scanner can help make the site more reliable for controversial topics, he said.
A spokesman for Wikipedia in Germany referred to the scanner tool as a "good development" and encouraged other researchers and people to download data from the online encyclopedia and snoop around. "There's surely plenty to discover," he said via e-mail.
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The Kiwi channel gathers for the 2020 Reseller News Women in ICT Awards
Hundreds of leaders from the New Zealand IT industry gathered at the Hilton in Auckland on 17 November to celebrate the finest female talent in the Kiwi channel and recognise the winners of the Reseller News Women in ICT Awards (WIICTA) 2020.
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I have a go making love all round my fry affiliate despondent BFF!
Hot big-busted Cougar Deauxma Gets sew in the sky Fucked unconnected with GF be attractive to!
Indian Desi mischievous wifey with husband chatting sloppy.


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Harrison mourns Joseph Cannella, judge and longtime councilman
"A man of his stature you just don't replace," Town Supervisor Ron Belmont
Mark Lungariello
Rockland/Westchester Journal News
HARRISON - Judge Joseph Cannella, whose reputation for studious preparation and an acute understanding of government and law made him a key leader in town public service for more than two decades, died Thursday. He was 66.
According to his family, he had a heart attack and had been hospitalized for several days.
Nancy Cannella, his wife of 44 years, described him as tireless in his service and always a willing counsel.
"He was a selfless man, who gave back to the community," she said. "He was the voice of reason all of the time."
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Cannella, a partner at the New York City law firm Eaton & Van Winkle, was sworn in as judge in January after he spent 14 years on the Town Board, which included stints as deputy mayor. His board tenure spanned the Great Recession and dire financial crises for Harrison, which he was credited for helping navigate by negotiating union contracts and labor givebacks.
Town Supervisor Ron Belmont said Town Hall was closed for Cannella's funeral Tuesday and ordered all flags on Harrison property to be flown at half-staff for the next month.
"We're going to do something for Joe, in his honor," Belmont told The Journal News/lohud, saying a renaming dedication is likely.
One option would involve a memorial of some kind to be placed at a planned multi-use development at the Harrison Train Station. Cannella took the lead in negotiating that deal with the Metropolitan Transportation Authority several years ago, Belmont said.
Cannella grew up in Queens and received his B.A., M.B.A. and J.D. from St. John's University. Later, he received an LL.M, a specialized law degree from Georgetown University.
After moving to Harrison with his family, he became involved as a recognized coach in the town's Little League. He spent eight years on the town Planning Board in 1990s, serving for a time as its chairman, before joining the Town Board on the Republican Party ticket in 2002.
During his funeral at St. Gregory's the Great, former colleagues on the Town Board remembered him during eulogies as a pragmatic, but strong-willed problem solver with a pronounced sense of right and wrong. He could analyze and discuss town problems late into the night, they said.
As the casket was taken out of the church, mourners gave a final, sustained round of applause.
His funeral procession, escorted by town police, shut down part of Halstead Avenue, the town's main thoroughfare, as a procession of cars passed under an American flag draped from firetruck ladders.
Dozens of uniformed cops volunteered to attend the funeral and escort the procession, the town supervisor said.
The judge's death leaves a hole in the fabric of the town, Belmont said, and leaves many in the town without his clear-sighted advice and insight.
"A man of his stature you just don't replace," Belmont said.
Cannella is survived by his wife, son Jonathan and two daughters, Kimberly and Ashley.
Twitter: @marklungariello


Intravenous sedatives and analgesics are commonly administered to mechanically ventilated children, however there is substantial variability in sedation practices in different intensive care units and in different countries around the world. The BabySPICE pilot study will evaluate the hypothesis that a sedation regimen based on safe, light sedation with dexmedetomidine as the primary sedative agent and in which benzodiazepine use is minimised, will lead to improved patient centred outcomes. The purpose of the BabySPICE Pilot RCT is to obtain preliminary data on the feasibility and safety of conducting a study that tests this hypothesis.
This is a pilot prospective randomised controlled trial that will be conducted in six tertiary paediatric intensive care units in Australia and New Zealand and will recruit 60 patients with a maximum of 15 patients from each participating site. The study will recruit patients ventilated for less than 12 hours, who are expected to remain ventilated at least 24 hours after enrolment AND need immediate and ongoing sedation. Patients will be recruited into one of two study groups. The intervention arm will receive dexmedetomidine as the primary agent, with the addition of second line sedatives as required. The use of benzodiazepines in this arm will be minimized and clonidine will not be used concurrently with dexmedetomidine. The control arm will have sedation according to usual practice as chosen by the treating clinician. This may include the use of clonidine according to standard unit practice but can only include dexmedetomodine as a last resort if all other agents have failed. In both groups, the default sedation level is light sedation, as defined by a target State Behaviour Scale (SBS) of -1 to +1, unless otherwise specified by the treating clinician. The primary outcome measure for the pilot study is to demonstrate separation between the intervention group (GpDex) and a 'wildtype' (usual practice) control group (GpStd) with respect to the proportion of patients achieving light sedation (SBS -1 to +1) in the first 48 hours of sedation in intensive care. Information from the Pilot RCT will be used to design a subsequent phase III trial.
Simon Erickson (Chair and Project Manager), Brian Anderson, John Awad, John Beca, Carmel Delzoppo, Marino Festa, Debbie Long, Mary Lou Morritt, Johnny Millar, Yahya Shehabi, Claire Sherring, and Tony Slater.
The project has been completed including follow up. Preliminary data analysis has been performed and a manuscript is currently in preparation.
The abstract has also been submitted for the ANZICS ASM 2018.


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Tetris Attack (SNES)
Kirby Super Star (SNES),
Super Mario 64 (N64),
Wayne Gretzky's 3D Hockey (N64)
Pilotwings 64 (N64)
Nintendo Power V87 is the August 1996 issue of Nintendo Power magazine. It features Tetris Attack on it's cover.
Ken Griffey, Jr.'s Winning Run
The first article in the magazine features the cover story, Tetris Attack. It provides explanations on the rules of the game and also a few strategies.
The next article is about Oscar. It gives information on the points and props as well as brief descriptions about a few of the levels.
Kirby Super Star is the subject of the next featured article. It provides maps for 7 different stages.
Wayne Gretzky's 3D Hockey
Wayne Gretzky's 3D Hockey box art
The first Nintendo 64 article is about Wayne Gretzky's 3D Hockey. It talks about the gameplay as well as production of the game. And it also discusses how hockey legend Wayne Gretzky himself was involved in the production.
The next featured Nintendo 64 game is Super Mario 64. It gives an overview of different aspects of the then-upcoming game.
Killer Instinct 2 (arcade game) Gargos lives!
AAAHH!! Real Monsters (SNES) Silly sounds
Boogerman: A Pick and Flick Adventure (SNES) Boss passwords
Bass Masters Classic: Pro Edition (SNES) Pro circuit password
Madden NFL 96 (SNES) Even more special teams
Star Trek: Starfleet Academy Starship Bridge Simulator (SNES) Secret Federation prototype
Nosferatu (SNES) Stage select and green crystal refill
Mega Man 7 (SNES) Hidden music
The Adventures of Batman & Robin (SNES) Unlimited lives and continues
Red Alarm (VB) More hidden icons
International Superstar Soccer Deluxe (SNES) All-star teams and extra skill points
Disney's Pocahontas (GB) All the colors of the wind
This "Previews" section gave readers brief 1-2 page looks at some popular upcoming games. This month, the previewed games were Saban's Power Rangers Zeo: Battle Racers (SNES), Zero Racers (VB), Donkey Kong Land 2 (GB), Marvel Super Heroes in War of the Gems (SNES), and Mole Mania (GB).
Fire Emblem: Genealogy of the Holy War box art
This article would give strategies for certain role-playing games. Some of the games listed here included Fire Emblem: Genealogy of the Holy War (Super Famicom) and Ogre Battle: The March of the Black Queen (SNES).
This article discusses the release of the Nintendo 64 in Japan.
The first Game Boy article features FIFA Soccer 97. It discusses the gameplay and a few strategies on the field.
The second Game Boy article is about Urban Strike. It lists the co-pilots and has details for the first 4 missions.
Counselor's Corner is a feature in which the writers of the magazine would respond to game-related questions in the hope of getting the player out of a tough spot in various games. The games featured in this issue are Donkey Kong Country 2: Diddy's Kong Quest (SNES), Chrono Trigger (SNES), Advanced Dungeons & Dragons: Eye of the Beholder (SNES), and Kirby's Dream Land 2 (GB).
The Incredible Shrinking Game Boy
This article talks about the then-upcoming Game Boy Pocket.
This article gives tips on defeating the "boss" enemy in various games, including Donkey Kong Country 2: Diddy's Kong Quest (SNES), Super Mario World 2: Yoshi's Island (SNES), Super Punch-Out!! (SNES), Super Adventure Island II (SNES), Nosferatu (SNES), Mortal Kombat 3 (SNES), and Castlevania: Dracula X (SNES).
Oscar (SNES) and Tetris Attack (SNES).
The Pak Watch section showcased games that were scheduled for release. It gave the reader a quick glance at future games. Some of the games seen in this section include Blast Corps (N64), Top Gear Rally (N64) and Donkey Kong Country 3: Dixie Kong's Double Trouble! (SNES).


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Home » climate and security » New Topic Guide: Conflict, Climate and Environment
New Topic Guide: Conflict, Climate and Environment
Evidence on Demand has created a new topic guide, "Conflict, Climate and Environment," by Katie Peters and Janani Vivekananda. Below is an overview of the guide and a list of the key messages. The guide provides an extensive overview of climate and conflict linkages, including knowledge gaps and suggestions for effective and sensitive policy-making. A PDF of the guide can be found on the Evidence on Demand website and is well worth a read.
The following is an overview of the Conflict, Climate and Environment guide via the Evidence on Demand website:
This Topic Guide will support DFID advisers in the Conflict, Security and Justice Cadres as well as the Humanitarian, Climate and Environment Cadres in gaining a greater understanding of the importance and complexity of the links between conflict, climate and environment. The Topic Guide focuses on violent conflict at the sub-national, national and trans-boundary level in relation to natural resources, climate variability, climate change and environmental change. The guide concentrates on longer-term development objectives to build resilience, support adaptation, create peace and address underlying causes of vulnerability.
Climate change (natural and man-made) is already having an impact on conflict, security and fragility. Climate related stressors have played a role in, for example, the ongoing political economy of conflict in Darfur and in food insecurity across the Sahel. Climate change has also been claimed to play a complicating role in more recent conflicts in the Arab Spring, though no conflict has a single motivating factor.
Climate change will continue to be a 'risk multiplier' of conflict, insecurity and fragility unless it is effectively embedded into the management of risk and building of resilience. The Intergovernmental Panel on Climate Change's Fifth Assessment Report affirms that the impact of climate change on human wellbeing, peace and security will worsen, especially for the poorest members of society. Many of the most affected live in fragile states where under-development is intractable and national capacity to manage climate risks is weak. In many countries, as climate change interacts with other features of the social, economic and political landscape, there is a high risk of political instability and violent conflict.
What determines whether (or how) climate change will lead to conflict lies in the 'intermediary factors' which affect the relationship between climate and conflict. The effects of climate change, such as more frequent natural disasters, long-term changes in precipitation and temperature and sea-level rise, could combine with other factors to increase the risk or prevalence of violent conflict. Increased vulnerability to conflict depends on a mix of factors: the context of poverty, effectiveness of governance and institutions, adaptive capacity, political inclusion and financial management. These factors affect the capacity of individuals and institutions to adapt to climate change and manage conflict in a peaceful manner.
There is much that can be done to ensure that climate change does not lead to increased conflict, insecurity and fragility, even in the absence of downscaled climate forecasts at the sub-national level. Addressing the root causes of vulnerability to climate change impacts – such as the lack of livelihood diversification, political marginalisation, unsustainable management of natural resources, weak or inflexible institutions and inequitable policy processes – can help ensure countries plan for uncertainty and peacefully manage a range of possible futures which climate change presents.
Taking account of the links between conflict, climate and environment is central to building resilience in an ever uncertain world. Better policy responses are required to ensure conflict prevention initiatives take account of climate changes, and to use climate change adaptation in support of peace and stability. Practical steps, such as ensuring that all climate change adaptation is conflict sensitive and that all conflict programming takes account of medium- to long-term climate change predictions, will help minimise the risk of interventions inadvertently doing harm. However, given the multiple levels of uncertainty – for example, how much average temperatures will rise, what the knock-on consequences will be on peace and security and how demographic changes will interact with these risks – a comprehensive risk management approach is required.
Gaps in the evidence exist on how to achieve multiple wins. There is a lack of well documented examples, at scale, on how to achieve 'multiple wins' in order to support resilience building. For example, what are the policies and programmes that have positive outcomes on peace, adaptation and development progress? Building resilience and managing risk is becoming the new mantra of the post-2015 era, bringing with it opportunity to improve policy action on the intersection of conflict, climate and environment.
The full guide is available here.
Tags: adaptation, climate change, conflict prevention, environment, fragile states, natural resources management, resilience, risk management, security, vulnerability
By Caitlin Werrell and Francesco Femia in climate and security on December 1, 2014 .
← Climate Security Q&A with Admiral Titley and Admiral Morisetti	Chairman US National Intelligence Council: Factoring In Climate Security →


From travel insurance to vaccinations, here's what to think about before you travel.
Start preparing for your trip, especially long trips, four to six weeks before you go.
Find out if you need travel vaccines and make sure your vaccinations are up-to-date.
If diseases such as malaria are a risk, you may need to start treatment before travelling.
Prepare a kit of travel health essentials, including sunscreen, painkillers and antiseptic.
Consider taking condoms with you to avoid the risk of buying fake, and potentially unsafe, brands when you get there.
For more information, read the Sun safety Q&A.
Whether you're off on a six-month trek to the Himalayas or a family holiday in Spain, it's vital to have the right travel insurance.
Make sure your policy covers your destination and the duration of your stay, as well as any specific activities you might do.
When travelling in Europe, make sure you have a valid European Health Insurance Card (EHIC).
The EHIC will entitle you to free or reduced-cost medical care. However, it won't cover you for everything that travel insurance can, such as emergency travel back to the UK.
If you think you may be at risk of developing deep vein thrombosis (DVT), seek advice from your doctor.
On long-haul flights, get up from your seat to walk around and stretch your legs whenever you can. Drink regularly, but avoid alcohol, and wear loose, comfortable clothes.
Jet lag is worse when you move from west to east because the body finds it harder to adapt to a shorter day than a longer one.
Travellers who take medication according to a strict timetable, such as insulin or oral contraceptives, should seek medical advice from a health professional before their journey.
Get tips on dealing with jet lag .


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Home » Decision Support in Medicine » Infectious Diseases
OVERVIEW: What every practitioner needs to know
Are you sure your patient has sepsis? What should you expect to find?
Sepsis is defined as a life-threatening organ dysfunction caused by an abnormal host response to infection. A subset of patients with sepsis will show signs of circulatory and metabolic abnormalities that can significantly increase mortality; these patients are considered to have septic shock.
For a patient to be classified as having systemic inflammatory response syndrome (SIRS), he or she must have more than one of the following clinical findings:
body temperature greater than 38 degrees Celsius or less than 36 degrees Celsius
heart rate greater than 90 beats per minute
respiratory rate greater than 20 breaths per minute or a carbon dioxide blood gas level greater than 32mm Hg
white blood cell count greater than 12,000 cells per liter or less than 4,000 cells per liter
Previously, severe sepsis was defined as sepsis with evidence of organ dysfunction, hypoperfusion, or hypotension. Based on recent recommendations, the term severse sepsis is no longer being recommended for use due to redundancy.
Newer tools, such as the Sequential Sepsis-Related Organ Failure Assessment (SOFA), are available to identify patients with sepsis induced organ dysfunction.
Symptoms are wide-ranging and can vary from patient to patient. They include, but are not limited to:
altered mental status (confusion, agitation, somnolence, etc.)
Physical findings can vary as well. Most patients with sepsis can have:
tachycardia (heart rate >100 beats per minute)
alterations in body temperature (fever or hypothermia)
altered blood pressure (hypertension or hypotension)
infected catheters
changes in mental status (obtundation, stupor, or coma)
petechiae
Indications of decreased tissue perfusion include, but are not limited to:
oliguria
altered mentation
delayed capillary refill
cool skin
clammy extremities
How did the patient develop sepsis? What was the primary source from which the infection spread?
Obtain a thorough history from the patient and/or family and caregivers. Look for recent surgeries or prosthetic device placements, as well as intravenous catheters (e.g., hemodialysis lines).
Infectious sources associated with sepsis are summarized in Table I.
Table I
Infectious etiologies associated with sepsis.
Which individuals are of greater risk of developing sepsis?
Individuals who are at greater risk of developing sepsis are:
neonates and infants (aged <1 year)
elderly patients (age >65 years)
patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome
patients with diabetes mellitus, renal failure, and hepatic failure
nursing home or long-term care facility residents
patients with recent exposure to antibiotics
burn or multiple-trauma victims
intravenous drug abusers
postoperative patients
patients with malignancies
patients receiving chemotherapy
Beware: there are other diseases that can mimic sepsis:
Differential diagnosis:
acute stroke
acute pulmonary embolism
acute hemorrhage
central fever (patients with head trauma and/or neurologic dysfunction)
diuretic-induced hypovolemia
drug fever
systemic lupus erythematosus flare
What laboratory studies should you order and what should you expect to find?
Results consistent with the diagnosis
Peripheral complete blood count: leukopenia or leukocytosis; low platelets; anemia
Liver tests: elevation of aspartate aminotransferase and/or alanine aminotransferase; low albumin; elevated bilirubin; elevated lactate
Coagulation factors: prolonged prothrombin or partial thromboplastin time; low fibrinogen
Basic metabolic panel: elevated blood urea nitrogen and/or creatinine; hyperglycemia
Urinalysis showing urinary tract infection
Arterial blood gas: low oxygen levels; metabolic (lactic) acidosis; respiratory alkalosis
Serum lactate: elevation can result from tissue hypoxia
Results that confirm the diagnosis
Blood cultures: positive organism (positive in approximately 30% of cases)
Ascitic fluid culture: positive organism (for patients with hepatic failure and/or underlying cirrhosis)
Catheter and/or indwelling device tip culture: positive organism
Urine Gram stain or urine culture: positive organism
What imaging studies will be helpful in making or excluding the diagnosis of sepsis?
The benefits of obtaining dedicated imaging scans need to be weighed against the risks of transporting potentially unstable patients with severe sepsis or septic shock.
Chest X-rays are useful to evaluate for pneumonia and can be ordered as portable in some hospitals.
Computed tomography scans can show abscesses, indwelling infections, or organ perforation.
What consult service or services would be helpful for making the diagnosis and assisting with treatment?
The Sequential (Sepsis-Related) Organ Failure Assessment Score can help identify patients developing organ dysfunction.
Infectious disease services can be helpful in elucidating sources of infection or in management of goal-directed therapy for resistant organisms.
Surgery can be helpful for sepsis caused by an abscess, necrosis, or device.
Nephrology can be helpful in cases of dialysis.
Rapid response teams can be helpful to facilitate transfer of patients to higher care settings.
If you decide the patient has sepsis, what therapies should you initiate immediately?
Key principles of therapy
Start broad spectrum antimicrobial treatment immediately.
Resuscitate with intravenous fluid.
If, despite adequate intravenous fluid, the patient remains hypotensive or hypoperfusing, start vasopressor support and/or steroid supplementation
Utilize the Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) scoring system to determine which patients are at a higher risk for mortality and may benefit from transfer to an intensive care setting.
Insert a Foley catheter (urinary catheter) if the patient does not have one already in order to adequately monitor urine output.
If I am not sure what pathogen is causing the infection what anti-infective should I order?
Antibiotic guidelines
Broad spectrum antimicrobial treatment is defined as a combination of antibiotics that act against a wide range of pathogens. This is especially important as most of the time, the infecting organism is not known. Most studies indicate starting antibiotics within the first hour of suspicion improves morbidity and mortality. This is particularly important in the preintensive care unit setting, such as emergency departments. Some suggest that for every additional hour before effective antibiotic therapy is instituted following initial hypotension, the survival rate decreases by 7.6% per hour on average. Empiric broad spectrum coverage may decrease risk of bacterial resistance and reduce the probability of antibiotic failure.
Obtain blood cultures, preferably from two different sites, prior to initiating antibiotics. One or more blood cultures should be percutaneous and, if the patient has vascular access device, then one blood culture should be obtained from that site.
Use antibiotics with broad spectrums of coverage, based on clinical presentation, probable source of infection, the patient's immune status, and underlying risk factors, as well as local epidemiologic factors, such as organism-resistance patterns. It is important to note whether a patient was previously exposed to antibiotics or previous culture results. Using inappropriate antibiotics increases risk of death in intensive care unit (ICU) bacteremia from 30 to 60% and from 70 to 100% in cases of gram-negative shock.
Many ICUs with a high frequency of multiresistant organisms are using two-drug empiric therapy for serious gram-negative infections until microbiological speciation and susceptibility data are available.
Reassess antimicrobial therapy daily.
Begin narrowing coverage as soon as pathogens are identified or with resolution of shock, usually within 48 to 72 hours. Experts suggest that there is no benefit to prolonged broad-spectrum coverage; in fact, this may actually increase chances of antibiotic resistance. Combination therapy should be continued for 3 to 5 days, with total duration of antibiotics between 7 to 10 days. Currently, there are no randomized controlled trials on de-escalation of therapy in patients with sepsis or septic shock.
Stop antimicrobial therapy if the cause of sepsis or shock is found to be noninfectious.
Begin source control as soon as possible after successful initial resuscitation.
Use patient allergy profiles to any antimicrobials to guide antibiotic choice (e.g., allergy to penicillins or sulfa drugs).
Specific recommendations
Pneumonia as source: add a fluoroquinolone.
Patients with splenectomies: be sure to cover for encapsulated organisms.
Neutropenic patients: cover for Pseudomonas and other resistant gram-negatives.
Resistant organisms in nosocomial setting:
increasing presence of methicillin-resistant Staphylococcus aureus: treat with vancomycin.
vancomycin-resistant Enterococcus (VRE): treat with linezolid, tigecycline, daptomycin, or quinupristin-dalfopristin.
Treatment options are summarized in Table II.
Table II:n
Treatment options for sepsis.
Aminoglycosides: Pharmacokinetic monitoring may be appropriate to prevent toxicity. Daily dosing is recommended.
Beta-lactams: More frequent dosing or continuous infusion is preferred. For example, piperacillin-tazobactam 3.375g every 6 hours should be given instead of 4.5g every 8 hours.
Amingoglycosides, fluoroquinolones, metronidazole, and amphotericin B are some anti-infective agents that have dose-dependent microbicidal efficacy. Conversely, beta-lactams and vancomycin work in a time-dependent mechanism to kill organisms.
What other therapies are helpful for reducing complications?
Initial fluid resuscitation over the first 6 hours, with titration to goals of central venous pressure (CVP) 8 to 12mm Hg (or 12-15mm Hg in mechanically ventilated patients or patients with pre-existing decreased ventricular compliance), mean arterial pressure (MAP) 65 to 90mm Hg, urine output greater than or equal to 0.5mL/kg/hour, or mixed venous oxygenation greater than or equal to 65%. Crystalloids or colloids can be used. Some newer studies are suggesting that a positive fluid balance over 4 days (measured with CVP >12mm Hg) may actually increase mortality.
Start with a fluid challenge of greater than or equal to 1,000mL of crystalloids or 300 to 500mL of colloids over 30 minutes.
Three recently published large multi-national studies have suggested no significant difference in mortality outcomes with early goal-directed therapy (ARISE 2014, ProCESS 2014, Mouncey et al 2015).
Vasopressor therapy and inotropes can be used alongside fluid to achieve MAP greater than or equal to 65mm Hg, in order to maintain perfusion. See next section on vasopressors.
Intravenous hydrocortisone can be initiated in adult patients with septic shock, though recent data is suggesting that intravenous steroids may not be better than placebo in terms of morbidity or mortality. Usual starting dose is 100mg every 8 hours. Steroids should be weaned when vasopressors are no longer required. Avoid dexamethasone if hydrocortisone is available, as this can lead to immediate and prolonged suppression of the hypothalamic-pituitary-adrenal axis. Hydrocortisone may not be feasible in many developing countries.
Transfuse red cells when hemoglobin is less than 7.0g/dL to a goal hemoglobin of 7.0 to 9.0g/dL. This increases oxygen delivery and has been shown to improve mortality in some cases.
Controversial or evolving therapies
Recombinant human activated protein C (rhAPC) has been shown to reduce mortality in patients with APACHE II scores greater than or equal to 25 or with multiorgan failure in two large randomized controlled trials. Activated protein C is a soluble, vitamin-K dependent anticoagulant that works by inactivating cofactors Va and VIIIa in the coagulation cascade, as well as plasminogen-activator inhibitor 1. It also has antiapoptotic activity, blocks productions of cytokines by monocytes, and blocks cell adhesion. Overall, it works by decreasing inflammation.
It is the only anticoagulant that has proved effective in patients with severe sepsis. One of the major adverse effects of activated protein C is an increased risk of significant, life-threatening hemorrhage. One study showed a 2.5 to 3% increased risk of hemorrhage, especially intracranial hemorrhage. Activated protein C should be avoided in patients with an international normalized ratio greater than 3, platelet counts of less than 30,000 per cubic millimeter, intracranial or intraspinal surgery within the last 2 months, severe head trauma, patients with epidural catheters, and intracranial neoplasm or mass lesion or evidence of cerebral herniation.
Measuring venous saturation of oxygen can be an indicator in evaluating cardiac function. If less than 2.5L/min/m2, consider starting dobutamine to increase cardiac output. This may not be feasible in many institutions.
Keep in mind that drug metabolism and pharmacokinetics may be altered in the intensive care setting. Patients with poor perfusion to the gut may have bowel edema and/or ileus, which would decrease absorption of oral antibiotics. In patients with volume overload, drugs that normally distribute to extracellular spaces may have lower than normal concentrations due to the presence of increased extracellular fluid. In these patients, maximal recommended dosing of antibiotics should be used in sepsis and septic shock.
Shock states can lower the glomerular filtration rate, and subsequently the clearance of certain anti-infective agents. Also, patients with increased cardiac output and low serum albumin may have increased drug clearance. On the other hand, burn victims and patients with sepsis alone can have an increased glomerular filtration rate. Infusion of albumin was not shown to reduce all-cause mortality in a randomized control trial, though this study may have been underpowered (Caironi et al 2014).
Measure antibiotic levels in ICU patients, when there is a low therapeutic index, and when there is a direct relationship between serum levels and efficacy or toxicity. Certain antibiotics have levels that can be followed, such as vancomycin and tobramycin.
Clinicians much watch for a response to antibiotics. Patients with chronic vascular insufficiency may need more penetrant drugs, such as fluoroquinolones, clindamycin, rifampicin, or metronidazole, or even revascularization procedures.
Abscesses often require surgical debridement. Smaller abscesses, such as anaerobic lung abscesses or small brain abscesses can be treated with prolonged antibiotics.
Controversy arises in terms of antibiotic antagonism, where some suggest that using a single agent with broad therapy may have better outcome than using multiple agents.
Source control to improve morbidity. This consists of using all measures to control the source of infection. Source control should be a balance between maximum efficacy and minimal physiologic changes. Source control in sepsis is summarized in Table III.
A randomized trial of rosuvastatin in patients with sepsis-associated acute respiratory distress syndrome did not show any significant reduction in in-hospital mortality (ARDS Clinical Trials Network 2014).
Table III.
Device removal
Definitive control
Abscess Necrotizing fasciitis Infected intravascular catheter Surgical resection of necrotic organ or perforated viscus
Thoracic empyema Pyelonephritis Urinary catheter Sigmoid resection for diverticulitis
Septic arthritis Cholangitis Infected intrauterine device Cholecystectomy for gangrenous cholecystitis
Mesenteric ischemia Infected pacemaker Clostridial myonecrosis
Mediastinitis
Adapted from Dellinger et al (Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296-327.) and Kumar et al (Sharma S, Kumar A. Antimicrobial management of sepsis and septic shock. Clin Chest Med. 2008; 29;677-87.).
Vasopressors
Goal is to maintain the MAP between 65mm Hg and 90mm Hg in order to maintain adequate tissue perfusion. MAP is considered the driving force for perfusion of most vital organs. The exact blood pressure goal to target in septic shock is uncertain. For example, patients with diastolic dysfunction, decreased ventricular compliance, elevated intra-abdominal pressures, and pulmonary hypertension can have different perfusion end points.
Remember to assess regional and global perfusion while on vasopressors. Variables to use to assess tissue perfusion include serum lactate levels, CVP, base deficit (as an indirect measure of lactic acidosis), and venous oxygen saturation.
Vasopressors can be used emergently to maintain perfusion, although fluid resuscitation is first and foremost. Remember to continue aggressive fluid resuscitation and wean vasopressors when appropriate.
Arterial cannula should be placed as soon as possible after vasopressor is started. This allows for more accurate blood pressure recordings, compared with using a blood pressure cuff.
There is ongoing debate as to which vasopressor agent is most effective. Generally, norepinephrine and dopamine are the first choice to correct hypotension in septic shock. Side effects overall include limb ischemia and necrosis.
Dose-dependent pharmacologic effects
Doses less than 5μg/hg/min: activates dopaminergic receptors, causing vasodilation of the renal and mesenteric circulation. However, current data suggests low-dose dopamine should not be used for renal protection in severe sepsis.
Doses between 5 to 10μg/kg/min: activates β-1 receptors, leading to cardiac contractility and causing increasing heart rate (subsequently perfusion).
Doses greater than 10μg/kg/min: activates α-1 adrenergic receptors, causing arterial vasoconstriction, which leads to elevated blood pressure.
Major side effects include tachycardia and arrhythmias.
Norepinephrine
α-adrenergic agonist, some β-adrenergic agonist effects
Dose is 0.01 to 3.3μg/kg/min
In studies where patients remained hypovolemic, norepinephrine was associated with renal ischemia
Selective α-1-adrenergic agonist
Rapid onset and short duration
Significant increase in urine output without change in serum creatinine
α-adrenergic and β-adrenergic agent; also increases oxygen delivery
Potential to decrease splanchnic blood flow. This can increase serum lactate concentrations
Side effects include tachycardia, tachyarrhythmias, ischemia, and hypoglycemia
Constricts vascular smooth muscle
Dose is 0.01 to 0.04 units per minute
Usually second line, though some studies are suggesting earlier initiation of vasopressin may improve outcomes
Side effects include coronary artery constriction leading to myocardial ischemia or infarction; especially in patients with severe coronary atherosclerosis
What complications could arise as a consequence of sepsis?
seeding of prosthetic valves or joints
prolonged hospitalization and/or rehabilitation
What should you tell the family about the patient's prognosis?
Sepsis has a high mortality rate, ranging from 19 to 56%.
Risk factors for poor outcomes include elderly and/or immunosuppressed patients. Mortality rates have been shown to increase from 10% in children to 38.4% in patients aged greater than 85 years.
What-if scenarios:
If you suspect a central intravenous-line infection as a source of sepsis, then remove the line as soon as possible and send the catheter tip for culture.
How do you contract sepsis and how frequent is this disease?
The occurrence of sepsis ranges from 2% to 11% in ICUs in the United States.
The incidence is estimated to increase approximately 1.5% each year, with 76 to 110 cases per year per 100,000 population.
In the United States, incidence is higher in men than in women and in the non-white population compared with the white population.
It is estimated that there are 750,000 cases of severe sepsis yearly in the United States, with lower rates suggested in European countries.
There is an increasing emergence of multidrug resistant gram-positive and gram-negative pathogens.
Average cost per case has ranged from $9,000 to $22,100. Surgical patients cost approximately $30,800. Intensive care patients cost more than patients with sepsis managed on the floors; they cost $29,900.
Total national hospital associated with care of patients with severe sepsis was $16.7 to $20 billion in the United States.
How do these pathogens cause sepsis?
Sepsis is thought to be the result of a complex combination of exaggerated inflammatory response to infection, but also has features suggestive of immunosuppression.
Tissue hypoxia causes a heightened inflammatory response and release of cytokines such as interleukin 1, interleukin 6, and tumor necrosis factor α. Hypoxia also causes mitochondrial and endothelial dysfunction. These cytokines then lead to myocardial dysfunction, which causes decreased cardiac output and further tissue hypoperfusion. Decreased blood flow to kidneys leads to acute kidney injury.
Diffuse epithelial injury leads to tissue edema by capillary leak.
Activation of inflammatory cascade leads to excess production of clotting factors and subsequent microvascular thrombosis.
Neutrophil recruitment leads to multiple tissue death.
Loss of delayed hypersensitivity.
What other additional laboratory findings may be ordered?
Cerebrospinal fluid can show meningitis.
Urine antigens to Streptococcus pneumoniae and Legionella pneumophila type 1 may be found in patients with pneumonia as a source of sepsis.
Studies are looking at methods of measuring oxygen desaturation in the hepatic vein; these studies are suggesting that the splenic circulation is susceptible to ischemia and may drive organ failure.
How can sepsis be prevented?
Early identification of sepsis and initiating treatment immediately can decrease chance of progression to septic shock, as well as instituting correct antimicrobial regimens. Despite widespread use of the SIRS criteria, one out of eight patients may still have severe sepsis that may be missed by just SIRS criteria alone.
The SOFA score, previously known as the Sepsis-related Organ Failure Assessment, has been shown to predict patients at a higher risk for mortality and can be used to triage patients to a higher level of care (see Table IV). Recent large-scale studies have shown that patients with an acute SOFA score change of 2 or more as a result of infection reflects an overall mortality risk of approximately 10%. The quick SOFA (qSOFA) tool combines a respiratory rate ≥ 22/min, altered mentation, and a systolic blood pressure ≤ 100 mm Hg as a simple bedside criteria to identify adult patients with suspected infection who have higher morbidity.
Unfractionated or low-molecular weight heparin for deep venous thrombosis prophylaxis, unless there are contraindications such as severe coagulopathy, active or recent bleeding, or thrombocytopenia. If anticoagulation cannot be given for deep venous thrombosis prophylaxis, then institute graduated compression stockings or intermittent compression devices unless contraindicated.
Encourage primary prevention in outpatient settings, such as obtaining influenza or pneumococcal vaccines, routine health care, etc.
Table IV:n
Sequential [Sepsis-Related] Organ Failure Assessment Score
WHAT'S THE EVIDENCE for specific management and treatment recommendations?
Dellinger, RP, Levy, MM, Carlet, JM. "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008". Crit Care Med. vol. 36. 2008. pp. 296-327. (Update on Surviving Sepsis Campaign from 2004 using Grades of Recommendation, Assessment, Development, and Evaluation via a consensus conference of experts. Categories include goal-directed therapy, broad-spectrum antimicrobials, culture data, source control, and adjunctive measures—including corticosteroids, vasopressors, activated protein C, and stress-dosed steroids.)
Machado, FR, Mazza, BF. "Improving mortality in sepsis: analysis of clinical trials". Shock. vol. 34. 2010. pp. 54-8. (Analysis of studies implementing Surviving Sepsis Campaign bundles (or protocols) and effect on ICU cost. Presents Latin American Sepsis Institute data for mortality related to sepsis as well as short reduction in mortality rate after implementation of Surviving Sepsis Campaign bundles.)
Levy, MM, Fink, MP, Marshall, JC. "2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. 2001". Crit Care Med. vol. 31. 2003. pp. 1250-6. (Signs and symptoms of sepsis, cell markers, cytokines, microbiologic data, and coagulation parameters that are associated with sepsis as defined by group of leading experts in a joint conference.)
Angus, DC, Wax, RS.. "Epidemiology of sepsis: an update". Crit Care Med. vol. 29. 2001. pp. S109-16. (Literature review of occurrence and hospital mortality of sepsis. Noted to show few population-based prospective cohort studies existed at this time to accurately determine risks and outcomes of sepsis. Reviews markers of inflammation and genetic predisposition that may be related to sepsis.)
Angus, DC, Linde-Zwirble, WT, Lidicker, J, Clermont, G, Carcillo, J, Pinsky, MR.. "Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care". Crit Care Med. vol. 29. 2001. pp. 1303-10. (Observational study compiling data from seven hospitals in 2005; study showing frequency of mortality in patients with severe sepsis as well as cost anlaysis.)
Burchardi, H, Schneider, H.. "Economic aspects of severe sepsis: a review of intensive care unit costs, cost of illness and cost effectiveness of therapy". Pharmacoeconomics. vol. 22. 2004. pp. 793-813. (Analysis of cost of ICU care of patients with severe sepsis as reported by multiple studies. Further discusses possibilities for cost containment in ICUs, including avoiding complications and introducing protocols.)
Siddiqui, S, Razzak, J.. "Early versus late preintensive care unit admission broad spectrum antibiotics for severe sepsis in adults". Cochrane Database of Systematic Reviews. 2010. pp. CD007081(Review article comparing early administration (<1 hour) of antibiotics versus late administration in patients with severe sepsis. However, despite broad search parameters, no randomized control studies were found that matched inclusion criteria.)
Robson, WP, Daniels, R.. "The Sepsis Six: helping patients to survive sepsis". Br J Nurs. vol. 17. 2008. pp. 16-21. (Discussion of early detection, education of nurses and junior physicians, and six major categories of early goal-directed therapy (including blood cultures, oxygen delivery, administration of intravenous fluids and antibiotics, checking lactate, and monitoring urine output). Also briefly analyzes cost of sepsis in United Kingdom hospital.)
Claessens, YE, Dhainaut, JF.. "Diagnosis and treatment of severe sepsis". Crit Care. vol. 11. 2007. pp. S2(Discusses Surviving Sepsis Guidelines in terms of early goal-directed therapy and focuses on limitations in implementation, including delayed diagnosis and/or treatment.)
Hollenberg, SM.. "Vasopressor support in septic shock". Chest. vol. 132. 2007. pp. 1678-87. (Review of the various vasopressors used in septic shock, including their mechanisms of action, doses, and complications.)
da Silva Ramos, FJ, Azevedo, LCP.. "Hemodynamic and perfusion end points for volemic resuscitation in sepsis". Shock. vol. 34. 2010. pp. 34-9. (Review evaluating utility of mean arterial pressure, central venous pressure, pulse pressure variation, serum lactate, base deficit, and venous oxygen saturation. Briefly reviews pathophysiology.)
Boyd, JH, Forbes, J, Nakada, TA, Walley, KR, Russell, JA.. "Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality". Crit Care Med. vol. 39. 2011. pp. 259-65. (Retrospective review of vasopressin in septic shock trial (VASST) patients who received intravenous fluids in the first four days showing increased mortality in patients with a cumulative positive fluid balance in 4 days.)
Zubert, S, Funk, DJ, Kumar, A.. "Antibiotics in sepsis and septic shock: like everything else in life, timing is everything". Crit Care Med. vol. 38. 2010. pp. 1211-12. (Discussion of previous studies that looked at early goal-directed therapy in patients with sepsis, reviewing limitations, and ultimately focusing on importance of early administration of therapy to decrease morbidity and mortality of severe sepsis and septic shock.)
Sprung, CL, Brezis, M, Goodman, S, Weiss, YG.. "Corticosteroid therapy for patients in septic shock: some progress in a difficult decision". Crit Care Med. vol. 39. 2011. pp. 571-4. (This study was a laboratory experiment using adrenal fasciculata-reticularis cells of rats and administering lipopolysaccharide with subsequent challenge with adrenocorticotropic hormone (ACTH). Study showed impaired production of steroids by cells pretreated with steroids as well as decreased response to ACTH stimulation in rats exposed to steroids; this suggests adrenal tolerance to steroids as a cause of adrenal insufficiency during sepsis.)
Barlow, G, Nathwani, D.. "Is antibiotic resistance a problem? A practical guide for hospital clinicians". Postgrad Med J. vol. 81. 2005. pp. 680-92. (Identifies risk factors with resistant organisms, including methicillin-resistant S. aureus colonization. Reviews resistant patterns of Clostridium difficile, community acquired pneumonia, skin and soft tissue infection, and urinary tract infections in the United Kingdom by review of literature.
Murdoch, DR.. "Microbiological patterns in sepsis: what happened in the last 20 years?". Int J Antimicrob Agents. vol. 34. 2009. pp. S5-8. (Review of microbial causes of sepsis, change in microbial patterns locally and globally, and effect of rise in prevalence of human immunodeficiency virus over the last 20 years.)
Sharma, S, Kumar, A.. "Antimicrobial management of sepsis and septic shock". Clin Chest Med. vol. 29. 2008. pp. 677-87. (After brief review of pathophysiology, discusses pharmacodynamics and rationale for broad-spectrum antimicrobials. Also focuses on drug-level monitoring, failure of antibiotics, and de-escalation of therapy.)
Gomes Silva, BN, Andriolo, RB, Atallah, AN, Salomão, R.. "De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock". Cochrane Database Syst Rev. 2010. pp. CD007934(Intervention review using varying search engines, comparing randomized controlled trials where antimicrobial regimen was de-escalated based on culture results to studies with standard therapy for patients with sepsis, severe sepsis, or septic shock. Primary outcome was mortality at 28 days; no direct evidence available for de-escalation was found.)
Nguyen, HB, Rivers, EP, Knoblich, BP, Jacobsen, G, Muzzin, A, Ressler, JA, Tomlanovich, MC.. "Early lactate clearance is associated with improved outcome in severe sepsis and septic shock". Crit Care Med. vol. 32. 2004. pp. 1637-42. (Prospective case series examining lactate clearance in patients with severe sepsis after 6 hours of emergency room intervention. Patients with early lactate clearance had decreased mortality rate.)
Gaieski, DF, Mikkelsen, ME, Band, RA. "Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department". Crit Care Med. vol. 38. 2010. pp. 1045-53. (Single center study analyzing association of early goal-directed therapy in 261 patients with severe sepsis or septic shock when therapy started in emergency room. Antibiotics administered within 1 hour of qualification had lower mortality rate.)
Bozza, FA, Carnevale, R, Japiassú, AM, Castro-Faria-Neto, HC, Angus, DC, Salluh, JI.. "Early fluid resuscitation in sepsis: evidence and perspectives". Shock. vol. 34. 2010. pp. 40-3. (Review of single randomized control-trial of early goal directed therapy for sepsis with a historical review of fluid resuscitation as well as potential mechanisms of improved clinical outcome with early fluid resuscitation. Briefly examines future studies pending.)
Spanos, A, Jhanji, S, Vivian-Smith, A, Harris, T, Pearse, RP.. "Early microvascular changes in sepsis and severe sepsis". Shock. vol. 33. 2010. pp. 387-91. (Single-center trial comparing perfusion parameters in patients admitted with sepsis and severe sepsis compared with healthy individuals. Patients with more severe disease had a lower proportion of perfused vessels, lower microvascular flow index, and lower perfused vessel density.)
Kumar, A, Safdar, N, Kethireddy, S, Chateua, D.. "A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study". Crit Care Med. vol. 38. 2010. pp. 1651-64. (Meta-analysis of randomized or observational studies in which high-risk patients were treated with combination antimicrobial agents versus low-risk patients as well as studies where monotherapy was administered. Of the 50 studies examined in the study, analysis suggested lower mortality in high-risk patients treated with combination antimicrobial therapy but higher mortality in low-risk patients treated with combination therapy.)
Rivers, E, Nguyen, B, Havstad, S. "Early goal-directed therapy in the treatment of severe sepsis and septic shock". N Engl J Med. vol. 345. 2001. pp. 1368-77. (Study randomizing patients with severe sepsis and septic shock to either early goal-directed therapy (within 6 hours) or standard therapy with examination of primary endpoint of in-hospital mortality. Patients in the early goal-directed group had 30% mortality compared with 46% in the control group.)
Kollef, MH, Sherman, G, Ward, S, Fraser, VJ.. "Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients". Chest. vol. 115. 1999. pp. 462-74. (A prospective, single-center cohort study examining the risk of inadequate antimicrobial treatment of community-acquired and nosocomial infections with hospital mortality rate. Patients at higher risk of receiving inadequate antibiotics included those with blood-stream infections, older age, increasing APACHE II scores, and previous administration of antibiotics.)
Hotchkiss, RS, Karl, IE.. "The pathophysiology and treatment of sepsis". N Engl J Med. vol. 348. 2003. pp. 138-50. (Review article analyzing current knowledge regarding immune system function and cytokines. Autopsy studies in patients who died of sepsis indicate decreased immune cells, which was further demonstrated in this study. Also briefly highlights therapies in sepsis—including glycemic control, activated protein C, corticosteroids, and volume resuscitation.)
Toussaint, S, Gerlach, H.. "Activated protein C for sepsis". N Engl J Med. vol. 361. 2009. pp. 2646-52. (Case followed by discussion of pathophysiology of sepsis, focusing on formation of procoagulant state, and pathophysiology of recombinant human activated protein C. Reviews current literature and studies using protein C and current guidelines.)
Wafaisade, A, Lefering, R, Bouillon, B. "Epidemiology and risk factors of sepsis after multiple trauma: an analysis of 29,829 patients from the Trauma Registry of the German Society for Trauma Surgery". Crit Care Med. vol. 39. 2011. pp. 621-8. (Retrospective cohort study examining incidence of sepsis in trauma patients; patients were collected from Trauma Registry of the German Society for Trauma Surgery and incidence of sepsis was noted to decrease over the study period. However, while the overall mortality of trauma patients decreased, patients with sepsis complicating trauma did not change. This suggests greater need for early detection of sepsis in trauma patients.)
Gustot, T.. "Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response". Curr Opin Crit Care. vol. 17. 2011. pp. 153-9. (Review article addressing current understanding of pathophysiology of systemic inflammatory response, sepsis, and severe sepsis. Includes review of inflammatory pathway and cytokines. Also discusses prognosis of sepsis and determinants of outcome of patients with sepsis.)
Callahan, LA, Supinski, GS.. "Sepsis-induced myopathy". Crit Care Med. vol. 37. 2009. pp. S354-67. (Review of current evidence of incidence of myopathy in ICU patients, with specific reviews of studies showing alterations in skeletal muscles and subcellular changes along with possible pathophysiologic mechanisms of such changes in septic patients. Clinical implications are addressed.)
Vincent, JL, Nelson, DR, Williams, MD.. "Is worsening multiple organ failure the cause of death in patients with severe sepsis?". Crit Care Med. vol. 39. 2011. pp. 1-6. (Retrospective analysis of multicenter database analyzing incidence of multiorgan failure, refractory shock, and respiratory failure as three leading causes of death in patients with severe sepsis.)
Russell, JA.. "Management of sepsis". N Engl J Med. vol. 355. 2006. pp. 1699-713. (Review article of pathophysiology of sepsis and therapies for early and late stages of sepsis.)
Vincent, JL, Baron, JF, Reinhart, K. "Anemia and blood transfusion in critically ill patients". JAMA. vol. 288. 2002. pp. 1499-507. (Multicenter prospective study examining frequency of blood draws, anemia, and transfusions in ICU patients with mortality. It was noted that patients who received transfusions had higher mortality and worsening organ function.)
Warren, HS, Suffredini, AF, Eichacker, PQ, Munford, RS.. "Risks and benefits of activated protein C treatment for severe sepsis". N Engl J Med. vol. 347. 2002. pp. 1027-30. (Brief review of activated protein C with detailed discussion of two major trials in use of protein C in sepsis. Reviews indications for protein C as well as risks of hemorrhage.)
Sprung, CL, Annane, D, Keh, D. "Hydrocortisone therapy for patients with septic shock". N Engl J Med. vol. 358. 2008. pp. 111-24. (Multicenter, randomized, placebo-controlled trial enrolling 499 patients with septic shock who were randomized to hydrocortisone 50mg every every 6 hours for 5 days versus placebo showed no signficant difference in mortality at 28 days.)
Mason, PE, Al-Khafaji, A, Milbrandt, EB, Suffoletto, BP, Huang, DT.. "CORTICUS: the end of unconditional love for steroid use?". Crit Care. vol. 13. 2009. pp. 309(Comparison of the two large studies examining steroid use in ICU patients. Recommendations including reserving steroid use for septic patients with hypotension unresponsive to fluid resuscitation and vasopressors.)
Chelazzi, C, Villa, G, De Gaudio, AR.. "Cardiorenal syndromes and sepsis". Int J Nephrol. vol. 2011. 2011. pp. 652967(Review of five types of cardiorenal syndrome, with focus on type 5, as associated with severe sepsis. This then reviews epidemiology, suspected pathophysiology, and treatment.)
Pea, F, Viale, P.. "Bench-to-bedside review: appropriate antibiotic therapy in severe sepsis and septic shock—does the dose matter?". Crit Care. vol. 13. 2009. pp. 1-13. (Review of basic principles of antimicrobial management, such as minimum inhibitory concentration. Further delineates common dosing of antimicrobials and renal dosing.)
De Waele, JJ.. "Early source control in sepsis". Langenbecks Arch Surg. vol. 395. 2010. pp. 489-94. (Review of rationale of early source control, specifically drainage, debridement and device removal, decompression, and restoration of anatomy, particularly for intra-abdominal infections. Calls for levels of urgency for source control.)
Micek, ST, Welch, EC, Khan, J, Pervez, M, Doherty, JA, Reichley, RM, Kollef, MH.. "Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to gram-negative bacteria: a retrospective analysis". Antimicrob Agents Chemother. vol. 54. 2010. pp. 1742-8. (Retrospective cohort study in patients receiving appropriate versus inappropriate initial antimicrobial therapy showed increased incidence of healthcare-associated nosocomial infections. These patients were also more likely to have kidney disease, diabetes, and prior antibiotic exposure in subgroup analysis.)
Wong, F, Bernardi, M, Balk, R. "Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club". Gut. vol. 54. 2005. pp. 718-25. (Review of current knowledge of sepsis, including definitions, epidemiology, pathophysiology, with a focus on how sepsis presents in patients with cirrhosis. Discusses gut translocation, spontaneous bacterial peritonitis, and recommendations on antibiotic prophylaxis.)
Sheu, CC, Gong, MN, Zhai, R. "Clinical characteristics and outcomes of sepsis-related vs non-sepsis-related ARDS". Chest. vol. 138. 2010. pp. 559-67. (Prospective cohort study comparing patients with sepsis-related acute respiratory distress syndrome (ARDS) and nonsepsis related ARDS in terms of disease severity, time to extubation, and overall mortality rate. It was suggested that patients with sepsis-related ARDS had poorer outcomes and higher disease severity.)
Kampmeier, TG, Rehberg, S, Westphal, M, Lange, M.. "Vasopressin in sepsis and septic shock". Minerva Anestesiol. vol. 76. 2010. pp. 844-50. (This article reviews the experiments and summaries of vasopressin use in sepsis and septic shock, including discussion of pathophysiology.)
Wilson, PG, Manji, M, Neoptolemos, JP.. "Acute pancreatitis as a model of sepsis". J Antimicrob Chemother. vol. 41. 1998. pp. 51-63. (Reviews details of pathophysiology of systemic inflammatory response syndrome and how pancreatitis presents as a form of SIRS and can mimic sepsis.)
Barton, JR, Sibai, BM.. "Severe sepsis and septic shock in pregnancy". Obstret Gynecol. vol. 120. 2012. pp. 689-706. (Review and case series of pregnant patients with severe sepsis and septic shock. Includes incidence, common causes, as well as management.)
Singer, M, Deutschman, CS, Warren Seymour, C, Shankar-Hari, M. "The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)". JAMA. vol. 315. 2016. pp. 801-810. (Most recent update to guidelines for definitions of sepsis.)
Vincent, J-L, Moreno, R, Takala, J, Willats, S. "The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure". Intensive Care Med.. vol. 22. 1999. pp. 707-710. (One of the original studies describing the SOFA tool and showing increased mortality with progressively higher SOFA scores).
Antonelli, M, DeBacker, D, Dorman, T, Kleinpell, R, Levy, M, Rhodes, A.. "Surviving Sepsis Campaign Responds to Sepsis-3.2016". pp. 1-2.
Kaukonen, K-M, Baily, M, Pilcher, D, Jamie Cooper, D, Bellomo, R.. "Systemic inflammatory response syndrome criteria in defining severe sepsis". N Engl J Med. vol. 372. 2015. pp. 1629-38. (A retrospective review of patients with SIRS criteria enrolled in the ANZICS Adult Patient Database that compared outcome measures in terms of morbidity and mortality. It showed that that mortality increased with increasing SIRS criteria and that SIRS criteria missed one out of eight patients with severe sepsis.)
Mouncey, PR, Osborn, TM, Power, GS, Harrison, DA, Sadique, Z, Grieve, RD. "Trial of Early, Goal-Directed Resuscitation for Septic Shock". N Engl J Med. vol. 372. 2015. pp. 1301-11. (A randomized, open, multicenter, parallel-group trial based in England. Patients were randomized 1:1 to early goal directed therapy or usual care. Ninety day mortality was not significantly different between the two groups).
"Goal-Directed Resuscitation for Patients with Early Septic Shock. The ARISE Investigators and the ANZICS Clinical Trials Group". N Engl J Med. vol. 371. 2014. pp. 1496-506. (A multicenter, prospective, randomized, parallel-group trial comparing early-goal directed therapy of protocol resuscitation versus standard of care of 1600 patients. Patients in the early-goal directed therapy group received more fluids in the first 6 hours and often received more blood transfusions and vasopressors. There were no significant differences in all-cause mortality at 90 days. There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.)
"A Randomized Trial of Protocol-Based Care for Early Septic Shock. The ProCESS investigators". N Engl J Med.. vol. 370. 2014. pp. 1683-93. (A multicenter, randomized trial in which patients were randomized 1:1:1 to either protocol-based early goal directed therapy, protocol-based standard therapy, or usual care. In-hospital mortality did not significantly differ between any of the groups.)
"Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome. The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network". N Engl J Med. vol. 370. 2014. pp. 2191-200. (A multicenter trial with patients requiring mechanical ventilation and pulmonary infiltrates with systemic inflammatory response syndrome who were randomized to receive 40 mg enteral rosuvastatin loading dose followed by 20 mg daily or placebo. There was no significant difference in in-hospital mortality at 60 days between the two groups.)
Caironi, P, Tognoni, G, Masson, S, Fumagalli, R. "Albumin Replacement in Patients with Severe Sepsis or Septic Shock". N Engl J Med.. vol. 370. 2014. pp. 1412-21. (A multicenter, randomized, controlled trial conducted by the Albumin Italian Outcome Sepsis (ALBIOS) study group where patients in Italy were randomly assigned to receive 20% albumin and crystalloid solution or crystalloid solution alone from start of study until day 28 or discharge from the intensive care unit. Daily albumin was infusion for goal serum albumin of 30 grams per liter or more. There was no significant difference in all-cause mortality at day 28 or day 90. However, the study may have been underpowered and the majority of patients were enrolled during later stages of sepsis.)
DRG CODES and expected length of stay
995.91 Sepsis
995.92 Severe sepsis
995.93 Systemic inflammatory response syndrome due to noninfectious process without acute organ dysfunction
995.94 Systemic inflammatory response syndrome due to noninfectious process with acute organ dysfunction
ICD 10 Codes: (Singer et al 2016)
R65.20 Sepsis
R65.21 Septic shock
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Chromoblastomycosis
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Bill O'Reilly dropped by another talent agency
by Tom Kludt @tomkludt October 26, 2017: 12:24 PM ET
Fox gave O'Reilly contract after $32 million settlement
Bill O'Reilly will be dropped by William Morris Endeavor, the talent agency that handles his book deals.
In a statement provided to CNN, a spokesman for WME said that the agency will "no longer represent Bill O'Reilly for future deals."
"It is our fiduciary responsibility to service the existing deals we have under contract, but we will not be working with him moving forward," the statement said.
It is unclear how much longer that deal will last, but it's yet more professional fallout for O'Reilly after the New York Times reported last weekend on a $32 million settlement paid to a woman who accused him of sexual misconduct. On Monday, O'Reilly was dropped by United Talent Agency. His television agent there represented him for decades.
The latest revelation came months after O'Reilly was sacked by Fox News, where he reigned as the top-rated host on cable news for years. The firing came after a separate Times story about multiple settlements paid to women who accused O'Reilly of sexual harassment or inappropriate behavior.
O'Reilly has decried the reports as an effort to remove him from the marketplace. His representative did not immediately respond to a request for comment.
The decision by WME could have implications on a major part of the O'Reilly enterprise. With several bestselling titles to his name, O'Reilly's success as an author nearly matched his broadcasting prowess.
His "Killing" franchise, a series of history books, have sold millions of copies. The latest, "Killing England," has topped the New York Times bestseller list for the last three weeks, though it hasn't sold as well as other titles in the series.
Before this week, the book deals were a rare source of stability for O'Reilly. Advertisers fled his show in droves following the Times' report in April, prompting Fox to let him go. But Henry Holt, O'Reilly's publisher, has stood by him.
CNNMoney (New York) First published October 26, 2017: 11:42 AM ET


001) This week I finally decided to bite the bullet and purchase a new jacket from Fat Face. It's a beauty and more than likely one of my most expensive clothing purchases to date. It's pretty cosy though!
002) On Saturday, my friend hosted her Halloween party. I'm not the type of person who goes all out for Halloween but I decided this year to go as a deer using one of the many tutorials on Youtube. Considering I didn't try it out before I left, it actually turned out ok.
003) On Monday, I finished reading 'Me before you' which was absolutely amazing. I managed to miss the film when it was out so I thought I would give the book a go. Loved it so much that I'm definitely going to pick up the 2nd one. Now I need a new read...any recommendations?
004) Between working full-time and heading to the gym, I miss a lot of TV so I have to rely on catch-up. This weekend I have managed to catch-up on Paranoid (which is incredible) and I've also just started The Level which is also really good.


We all know that fast foods are loaded with bad fats, chemical preservatives, carbs, sugar, and calories. But now there is another reason to stay away from the stuff.
Researchers from the Silent Spring Institute in Newton, Mass., tested more than 400 fast food wrappers and boxes. They came from 27 chain restaurants across the country.
PFOA and PFOS are added to paper to stop greasy foods from soaking through packaging. But the chemicals leach into food, scientists say. U.S. manufacturers are supposed to have phased out fluorine compounds in food packaging… That's why researchers were surprised to find so many wrappers and boxes still contain the toxic chemicals.
Why is fluorine so common if wrapper companies no longer use it?
It's because many wrappers are imported. And foreign manufacturers still use PFOA and PFOS. Plus, there are huge inventories of old wrappers in the U.S. that contain the damaging substances.
What's more, many manufacturers use recycled paper for fast food wrappers. The old fluorinated paper often ends up being processed to make new packaging.
The study's lead researcher is environmental chemist Laurel Schaider. She noted that about one-third of U.S. children eat fast food every day.
The half-life of fluorine compounds in your body is up to 3 ½ years, said Schaider. Besides food wrappers, PFOS and PFOA are used to make nonstick cookware and stain-resistant carpets and fabrics.
Her study recently was published in the journal Environmental Science & Technology.
Don't expect fast food restaurants to clean up their act any time soon. Researchers asked the 27 chains included in the study about toxins in their packaging. Only two companies responded.
One said absolutely none of their packaging contained fluorinated chemicals. Tests showed it did.
Another claimed its packaging vendor said its wrappers had no fluorine. Tests showed they did.
Previously, we warned you that pizza boxes often contain PFAS.
Remove the food from the wrapper or box as soon as possible.
Never store leftover fast food in the original wrapper.
If some of the food, such as the cheese on a burger, has soaked onto the wrapper, discard that part.
Ask your server to put French fries, chicken fingers, or other small food items in a paper cup. As we mentioned earlier, cups don't contain fluorinated compounds.
If you are eating in the restaurant, ask that your food not be wrapped and be served on a plate instead.
Of course, the best strategy is to avoid fast food altogether. It's just about the worst thing you eat. It may be cheap and convenient… But is it worth your health?


text:
Erratum: In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119)
Bryan Killinger, Lee Marshall, Diptaman Chatterjee, Yaping Chu, Jose Bras, Rita Guerreiro, Jeffrey H. Kordower
Life Sciences, School of (SOLS)
The authors note that Fig. 4 appeared incorrectly. The order of column labels for panel C was inadvertently reversed during formatting. The authors note that the error does not change the conclusions or results of the article. The corrected figure and its legend appear below. The online version has been corrected.
Dive into the research topics of 'Erratum: In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119)'. Together they form a unique fingerprint.
Molecular Pathology Medicine & Life Sciences 100%
Killinger, B., Marshall, L., Chatterjee, D., Chu, Y., Bras, J., Guerreiro, R., & Kordower, J. H. (2022). Erratum: In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119). Proceedings of the National Academy of Sciences of the United States of America, 119(28), [e2209742119]. https://doi.org/10.1073/pnas.2209742119
Erratum : In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119). / Killinger, Bryan; Marshall, Lee; Chatterjee, Diptaman et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 28, e2209742119, 12.07.2022.
Killinger, B, Marshall, L, Chatterjee, D, Chu, Y, Bras, J, Guerreiro, R & Kordower, JH 2022, 'Erratum: In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119)', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 28, e2209742119. https://doi.org/10.1073/pnas.2209742119
Killinger B, Marshall L, Chatterjee D, Chu Y, Bras J, Guerreiro R et al. Erratum: In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119). Proceedings of the National Academy of Sciences of the United States of America. 2022 Jul 12;119(28):e2209742119. doi: 10.1073/pnas.2209742119
Killinger, Bryan ; Marshall, Lee ; Chatterjee, Diptaman et al. / Erratum : In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain (PNAS (2022) 119:28 (e2209742119) DOI: 10.1073/pnas.2114405119). In: Proceedings of the National Academy of Sciences of the United States of America. 2022 ; Vol. 119, No. 28.
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Driving Under the Influence is a serious crime with potentially lifelong repercussions. If you have been charged with a DUI in Coalinga California you are going to need a dependable DUI lawyer who specializes in fighting DUI charges.
DUI Lawyers in Coalinga Will Work With You to Lay Out Options and a Course of Action for your DUI.
The penalties and fees associated with a DUI conviction can be steep. That's why obtaining the help of a reliable DUI attorney can make all the difference. With their understanding of the law, a DUI attorney can help you negotiate for reduced or dismissed charges. Coalinga, California DUI attorneys are available to answer any questions you have about your options.


Stevensville, MD 21666. The USPTO has given the DRAGON trademark serial number of 74480962.
DRAGON sells goods and services of pick-ups for electric guitars. This logo and TradeMark was filed on January 21, 1994 and was first used on January 01, 1992.


text:
Other requirements relating to selected fundraising activities
Inc: A Guide for Incorporated Associations in Western Australia
Introduction to the INC Guide
Introduction to incorporated associations
Becoming an incorporated association
The management committee
Altering the rules
Resolving complaints and disputes
Accounts and auditing
Fundraising and grants
Employment and volunteering
Risk management and safety
Deregistering an incorporated association
Regulation of fundraising activities
Fundraising for charitable purposes
Australian Charities and Not-for profit Commission (ACNC)
Other matters for consideration
Street collections
The Street Collections (Regulation) Act 1940 applies to any organisation conducting a street collection in the metropolitan area. A 'public street' includes private land used by the public for pedestrian traffic. The car parks and footpaths outside a shopping centre are therefore considered to be a street for the purposes of street collections.
Associations in regional areas should check with their local council whether there are any requirements for conducting a street collection.
A street collection permit is required whether or not the proceeds are to be used for a charitable purpose. Permits are obtained from Consumer Protection. The application must set out details of the purpose and locality of the street collection, and any other relevant information. Consumer Protection requires at least six weeks' notice to process the application and issue the permit.
See Consumer Protection's website for more information about street collections or to download an application form.
Door-to-door collections
An association with a charitable collections licence may carry out door to door collections from households between the hours of 9am and 6pm on Mondays to Saturdays. All collectors must be over 16 years old and must wear an identity badge.
More information about the requirements of collecting from private residences is available on Consumer Protection's website.
Fundraising in shopping centres
Shopping centres are good places for raising funds because of the large numbers of people passing through. Shopping centres have their own policies and procedures for providing fundraising space and you should contact the centre management for more information and permission.
Lotteries and games
The Gaming and Wagering Commission Act 1987 allows permits to be issued to charitable groups, community based organisations and sporting bodies for the purpose of raising funds from gaming related activities such as:
lotteries (raffles);
trade promotion (e.g. colouring in competition or entries drawn randomly);
video lottery terminals;
bingo and two-up;
sweepstakes and gaming functions; and
football tipping competitions and minor fundraising activities.
Associations wishing to raise funds from one of these activities will in most cases need to obtain a permit from the Department of Local Government, Sport and Cultural Industries - Racing, Gaming and Liquor Division (RGL). There are different application forms, conditions and fees for each lottery and gaming activity and more information is available online.
Selling food at fundraising events
Selling food is a very popular and profitable way of raising funds, whether it is a cake sale, a sausage sizzle or a large food and wine festival. However, preparing and selling food requires very careful handling and preparation for reasons of hygiene and safety.
Associations that are planning to organise temporary food stalls need to obtain a permit from their local council. Councils will also be able to provide the association with general guidelines on preparing and selling food. Ask to speak to the environmental health officer.
Food Standards Australia New Zealand also have fact sheets for charity and community based organisations on matters relating to food safety, including a specific fact sheet on sausage sizzles and barbeques.
Serving alcohol at fundraising events
If a fundraising activity or event includes selling and supplying alcohol, it will be necessary to obtain a liquor licence. Associations organising fundraising events at which liquor will be sold will need to apply for an occasional licence. This is a licence for people/associations that do not hold any other licence under the Liquor Control Act 1988.
An occasional licence permits the sale of liquor at a function, which means a 'gathering, occasion or event, including a sporting contest, show, exhibition, trade or other fair or reception, at which liquor is sold and supplied.
For more information about these licensing requirements, associations should contact Racing, Gaming and Liquor:
Email: rgl@dlgsc.wa.gov.au
Website: www.rgl.wa.gov.au.
Address: PO Box 8349 Perth Business Centre WA 6849


You've probably seen the Fein Multimaster infomercial on late-night TV. Come see the real thing in action at Highland Woodworking this Saturday, Feb. 7. FEIN's engineers have added almost every conceivable function to this safe, vibration-free power tool. The Fein Multimaster is truly one of those rare tools that earns the undisputed title of "the best there is". It's a great sander, bringing fast, high-quality finishing into places that no full-size sander can reach. Fein's industrial-quality 2.3 amp motor (variable speed) drives the machine spindle at speeds from 11,000 to 20,000 opm, making this far and away the most efficient and smoothest-running tool in its class. With accessories, it's a saw that cuts wood and metal, scrapes paint, performs precision sanding, and much more. It can save you both time and money on a wide variety of home improvement and repair jobs. Come see it in action. We think you'll be impressed. Join us for a fun and educational visit to Highland Woodworking's unique Atlanta store.
All Saturday morning demonstrations take place in Highland Woodworking's retail store in Atlanta, Georgia and begin at 10:00am Eastern Time.
1045 N. Highland Ave, Atlanta, GA 30306.