Culture

If you're about to run headfirst into something, your reflex might be to tense your neck and stabilize your noggin. But according to new research from Stanford University that may not be the best way to stave off a concussion. Instead, the findings suggest that your head's position is more important than whether you are tensing your neck.

It all comes down to how your head accelerates backward after impact, which some think is the major factor controlling concussion risk. The work was published Aug. 20 in IEEE Transactions on Biomedical Engineering.

"We found it really interesting that your soft tissue - muscles, ligaments and tendons - isn't doing much to dictate how your head is rotating immediately after an impact," said Michael Fanton, lead author on the paper and graduate student in the lab of David Camarillo, assistant professor of bioengineering. "Whereas even a few degrees of change in your head-neck angle can really alter how much your head is rotated and therefore, probably, your risk of concussion."

The researchers made their discovery in a model of the human head and neck, but confirmed what they found in a similar model of a woodpecker, which can endure extreme accelerations when pecking holes. It turns out they too may be protected in part by the angle of their pecking.

A big surprise

In a previous study led by Calvin Kuo, who is a co-author on the new paper and graduated with his PhD this spring, the group tied miniature weights to people's heads to tilt them backward. They then monitored how the head moved after participants either relaxed or tensed their necks. From this, the group constructed a simple computer model that recreated the way the head tilts forward and backward.

The researchers ran simulations with this model that replicated low-impact forces and found tense neck muscles slightly reduced head acceleration. But they also extended those simulations to include higher-force impacts - the kinds that could lead to concussion, such as what someone might experience falling off a bike - with much different results. When looking at fast, hard impacts, it does not seem to matter whether the neck muscles are tensed or relaxed.

"Originally, we thought your neck muscles could affect head acceleration and we wanted to figure out if that offered another strategy for reducing brain injury," Fanton said. "It was surprising that in these shorter-duration impacts, the neck muscles are not doing a whole lot."

The importance of positioning

The researchers were also curious whether head and neck positioning could alter front-to-back acceleration after a hard, fast hit. They ran their simulations with the head positioned at a wide variety of angles and found that small variations in position could mean the difference between high and low concussion risk. Their results showed that both the angle of the head and where it is hit affect the subsequent rotation of the head.

All this raised the question of how woodpeckers are able to withstand so much pounding - thought to produce head-on accelerations 10 times greater than those that cause severe concussions in athletes. So, the researchers created a simplified head and neck model of a woodpecker and ran it through the same positioning tests they had run in the human simulations. What they found is that small changes in position could substantially change the head acceleration the bird experienced. When the researchers aligned their model in the way real woodpeckers hold themselves as they peck, they noticed very low rotational acceleration.

However, the group cautioned that position alone likely doesn't explain the woodpecker's ability to withstand these forces. Scientists have suggested the size of their brains and features of their beak may be mitigating factors.

Focusing on prevention

Although the Camarillo lab and others in the field are finding that the neck muscles and ligaments might not prevent the kinds of head movement that lead to concussions, neck positioning is not a simple solution. Positions that could prevent concussions might make people more susceptible to other injuries, such as paralysis, and what protects one person could potentially raise the injury risk of another person involved in the same impact.

"Discovering how sensitive the head is to slight changes in positioning has implications on design of helmets and other protective equipment," Camarillo said. "For example, could the facemask in football be offering a lever arm that adds to the rotation of the head and therefore risk of concussion? Are downhill mountain bike helmets protecting the chin at the cost of the brain? We hope to use this model we have developed to determine better design geometry of helmets and potentially for input to coaching on how to brace for impact."

Ultimately, Camarillo is hoping this kind of modeling work can aid in developing better ways of preventing head injuries.

New research published in the August edition of the Journal of the American College of Cardiology's Heart Failure issue found significant correlations between blood levels of EPA plus DHA omega-3s in "cognitive" (as opposed to "somatic") depression among heart failure subjects. (Cognitive depression would include symptoms like sadness and pessimism, whereas somatic would include manifestations such as fatigue and sleep disturbances.)

This randomized controlled pilot study was designed to investigate the effects of supplemental omega-3s (EPA and DHA) on depressive and psychomotor symptoms in people with chronic heart failure and depression.

The study included 108 subjects who were assigned to one of three groups each taking 2 grams per day of either 1) a 2:1 mg EPA/DHA supplement; 2) a high EPA product; or 3) a placebo. The study lasted 12 weeks with blood testing (i.e., Omega-3 Index, RBC levels of EPA and DHA) completed pre- and post-supplementation.

The Omega-3 Index reached 6.79% in the 2:1 EPA/DHA group, 6.32% in the EPA only group, and 4.61% in the placebo group. In those who were determined to have taken at least 70% of their capsules and finish all testing (n=80), these values were 7.32%, 7.11%, and 4.42%, respectively. This indicates that the dose (and compliance) were both adequate to significantly improve the Omega-3 Index in only three months.

The social functioning sub-score of the SF-36, a short general health survey, was significantly improved on the 2:1 EPA/DHA supplement and tended to improve with the high EPA supplement.

Significant correlations between the Omega-3 Index and measures of cognitive depression where also found. More specifically, a higher Omega-3 Index was related to lower cognitive depression scores on the Beck Depression Inventory-II (BDI-II), which is the most widely used instrument for detecting depression.

While these findings are of interest, there are a few caveats. First, this was a pilot study, so the p-values weren't adjusted for multiple comparisons, meaning that there is a higher likelihood that these were chance findings, (i.e. 1 of 19 outcomes was different between intervention and placebo arms).

Second, possibly because the study was relatively small with limited power, there was no significant effect of either omega-3 formulation on a variety of psychological measurements, in particular on the Hamilton Depression Score (HAM-D). So the primary findings related to correlations between changes in the Omega-3 Index and the BDI-II cognitive depression metric.

Commenting on the treatment vs. prevention dilemma frequently faced by nutritionals like omega-3s was Dr. Bill Harris, one of the study's authors and the co-inventor of the Omega-3 Index test. "This was a study in already depressed individuals, which meant the researchers are looking to high-dose (although it could have been higher) omega-3 supplements to improve depressive symptoms, like a drug," he said.

"Generally, we think of the function of omega-3s as preventative rather than as treatment. If used as treatment, the dose must be fairly high (4 grams is a typical 'drug' dose) and blood levels must be measured," Dr. Harris continued. "In their larger follow-up study, I would recommend they choose just one of the supplements (probably the pure EPA product) and increase the dose and duration of the study."

The authors were also exploring a few different supplement options, focusing on recent evidence that EPA might be more effective for treating depression while DHA may be better for general cognition. "From this study, it's not clear to me that one supplement type was better than the other," Dr. Harris said, adding, "However, linking higher blood levels of omega-3s to improved depression symptoms in people with both depression and heart failure is encouraging and hopefully leads to better treatment for their conditions."

Few studies have explored health professionals' understanding of racism in healthcare, and how they manage it in practice. A new Journal of Advanced Nursing study examined the issue through five focus group discussions with 31 maternal, child, and family health nurses working across metropolitan South Australia. These clinicians represent the core professional group working with infants and families in the first years of life.

The study explored how nurses make sense of racism in practice and contribute to ensuring that children from diverse racial and ethnic backgrounds do not accumulate further disadvantage in their lives through culturally unsafe healthcare practice.

The investigators found mixed understandings and misunderstandings about the nature of racism in practice. Also, where structural racism was identified, participants did not feel capable to challenge it. The findings suggest an urgent need for the introduction of anti-discriminatory education and training in the nursing workforce.

"Child health nurses work extremely hard to partner with the families with whom they work, but their practice is sometimes compromised because the frameworks used in their primary education is outdated. These results show that we urgently need interactive and sustained anti-racist education in pre-service, graduate, and workplace education," said author Dr. Julian Grant, of Flinders University, in Adelaide, South Australia. "Most importantly we need further research to find out what anti-racist approaches work best for Australian children and families."

In the Respirology study, investigators identified strong associations between several measures of OSA severity and higher total cholesterol, higher LDL-cholesterol, elevated triglycerides, and lower HDL-cholesterol. Lipid status was influenced by geographical location with the highest total cholesterol concentration recorded in Northern Europe.

The analysis included 8592 adults across Europe who were not diagnosed with hyperlipidaemia and were not taking lipid-lowering drugs.

"Our data clearly suggest that sleep apnoea may have a negative impact on lipid levels, which may in part explain the association between sleep apnoea and increased risk for cardiovascular disease," said senior author Dr. Ludger Grote, of Gothenburg University, in Sweden. "Patients with sleep apnoea therefore need careful management of all cardiovascular risk factors including hyperlipidaema."

BLOOMINGTON, Ind. -- Results of a new behavioral study into what influences the decision to recall a defective product found that medical device firm managers may rely on their physician-customers to screen out detectable defects, in lieu of issuing a recall.

The study also found that some managers appear to hesitate to recall a product until the root cause of the defect is clearly understood, because this can reduce recall costs to the firm.

The study, performed by professors at the Indiana University Kelley School of Business and the University of Minnesota's Carlson School of Management, has led to changes at the medical device firms that participated in the study and has attracted interest from leadership at the Food and Drug Administration. The FDA expressed interest in using this research to improve how they oversee medical device product quality.

Their research, published in the Journal of Operations Management, is the first behavioral study using actual industry managers to study what influences voluntary product recall decisions, an important new field of study considering the prevalence and customer safety impact of product recalls across multiple industries.

"The decision to recall a product can significantly affect an operations manager's career, the credibility and financial performance of the firm, and the safety of customers," the authors wrote. "Surprisingly, the FDA does not clearly specify how a manager should integrate the multiple, and potentially conflicting, criteria influencing whether or not to recall a product. Consequently, managers use individual judgment in arriving at recall decisions."

George Ball, the lead author and an assistant professor of operations and decision technologies at the Kelley School of Business, and his two co-authors performed a randomized behavioral experiment with medical device industry managers who make recall decisions in practice.

A key finding of the study is that "medical device industry managers appear to trust physicians to screen out defects on behalf of the firm, meaning that when the defect is detectable to the physician, managers are less likely to recall," Ball said. "This is because of a perception of increased patient safety when defects are detectable."

Ball and his colleagues -- Rachna Shah, associate professor of supply chain and operations; and Karen Donohue, Board of Overseers Professor of supply chain and operations, both at the Carlson School -- also found that managers often hesitated to recall until they first understand the root cause of the product defect.

After working closely with these managers, Shah said they observed that, "most of these managers are very technically oriented, and they want to know 'why' before they take an action that could be very costly both in direct financial consequences and in reputational harm. Waiting to understand root cause before choosing to recall, however, is not required by the FDA."

The researchers also found a relationship between a manager's cognition and their recall decision. In particular, managers with high cognitive reflection issued fewer recalls. The ability to first reflect, before making a quick, intuitive decision, may lead to fewer recalls because such reflective individuals have a tendency to seek out more information before reaching a decision. Non-reflective, intuitive managers, conversely, were influenced by relational factors such as their gender, work experience and perception of their firm's relationship with the FDA.

While the paper focuses on operations at medical device manufacturers, the authors believe that the findings have broader applications. "Any industry in which the supply chain has multiple stages where quality can be observed and controlled may be susceptible to the study's conclusions," said Donohue. "For example, auto firms may trust their dealers to catch their mistakes before selling their cars to the final customer."

A (wo)man is only as good as his or her tools. In the case of soil scientists, they are only as good as the tools and methods they use. And when it comes to estimating soil organic carbon stocks, new research shows not all tools give the same results.

Soil organic carbon stocks are the amount of organic carbon found in soil. There are several common ways of measuring these stocks. Until now they were all believed to give pretty much the same results. Cole Gross, a graduate student in the Department of Renewable Resources at the University of Alberta, questioned this commonly-held assumption.

Gross explains that all organic materials found in soils are in some way from a living thing, such as decomposing plants and animals. This type of material is known as soil organic matter and about half of its mass is carbon. The amount of soil organic carbon differs from soil to soil, location to location.

"The ability to accurately measure soil organic carbon stocks and compare changes over time will help us make the best decisions about land use and management practices, which could ultimately improve soil health and productivity," Gross says. "If we can increase our understanding of soil organic carbon, we will also increase our understanding of climate-carbon feedbacks and better our climate models. Unreliable data regarding soil organic carbon stocks could lead to misconceptions about how land use, management, or climate change affects soil organic carbon."

Three measurements commonly used are clod, core, and excavation. For the clod method, a scientist takes a clod of soil from the surface or another specific depth and takes it to the lab for chemical analysis. The core method uses a hollow tube to pull a core of soil from a specific depth for analysis. The excavation method is the least common of the three, as it requires the most time and labor. However, it is considered the most accurate of the methods. It involves digging a large pit to get at a large amount of soil.

Although many believe the results of these three methods are similar, Gross found many key differences. He and his team found that the most commonly used method, the core method, greatly underestimated the soil organic carbon stock. Most of this difference occurred in soil deeper than 20 centimeters (just under 8 inches), which Gross says holds most of the soil organic carbon stock.

"Our results suggest that regional and global soil organic carbon stocks may be largely underestimated due to shallow sampling and the frequent use of core methods," he explains. "We found that these common soil sampling methods gave significantly different results and should not be assumed to be interchangeable."

Gross explains that the tools and methods soil scientists use are as important, if not more important, than the data they provide.

"For much of the work that we do, small errors in the first steps of a long process can amplify later in the process," he says. "It is always important to look back and check assumptions and the accuracy of methods, even if these methods have been accepted for a long time."

Based on the research team's findings, Gross recommends that the potential for the core method to underestimate soil mass be determined in a given soil and then adjusted to account for this. Additionally, they found that the clod method can be used as a standard reference for soil mass measurements in non-rocky soils.

"The inspiration behind this study was a bit serendipitous," he says. "As a fairly new soil scientist, when the soil sampling core I was using broke in the field, I was instructed to use the clod method and told that the methods were interchangeable. This seemed curious to me and inspired my research into different soil sampling methods, which ultimately led to this study."

Antibiotics - medicines that treat bacterial infections - have saved millions of lives worldwide since their discovery in the early 20th century. When we fill a prescription at the doctor's office or pharmacy today, most of us take for granted that these commonly prescribed medicines are real, and of good quality.

But in the developing world, the manufacture and the distribution of substandard, nonlegitimate medicines is widespread. The World Health Organization estimates that up to 10 percent of all drugs worldwide could be falsified, with up to 50 percent of those some form of antibiotics. A counterfeit or diluted antibiotic can not only endanger an unwitting patient, but can also contribute to the wider problem of antimicrobial resistance.

A Colorado State University laboratory is putting chemistry to work on a simple, inexpensive way to identify such falsified and substandard antibiotics, offering a practical solution to a very real problem. The researchers have created a paper-based test that can quickly determine whether an antibiotic sample is appropriate strength, or diluted with filler substances like baking soda. Similar to the mechanism of a home pregnancy test, a strip of paper turns a distinctive color if a falsified antibiotic is present.

It's the latest paper-based chemical assay developed in the lab of Chuck Henry, professor in the Department of Chemistry. Researchers including first author Kat Boehle, a recently graduated Ph.D. student, describe the invention in ACS Sensors.

"In this country, we take for granted that our antibiotics are good - we don't even think twice," Boehle said. "But counterfeit and substandard antibiotics are an extremely common thing in other parts of the world. The goal of this project has been to make a cheap detection device that is easy to use; our device costs literally a quarter to make."

Here's how it works: Bacteria naturally produce an enzyme that can give them resistance to antibiotics by chemically binding to portions of the antibiotic molecule. The researchers used this very enzyme, called beta-lactamase, to empower their device to detect the presence of antibiotics in a given sample.

For the test, the user dissolves the antibiotic in water, and adds the solution to a small paper device. The paper contains a molecule called nitrocefin that changes color when it reacts with the enzyme. In this setup, the antibiotic and the nitrocefin on the paper are in competition to bind with the enzyme in a detection zone.

With a good antibiotic dose, there is little color change in the paper strip, because the antibiotic outcompetes the nitrocefin and successfully binds with the beta-lactamase enzyme. But in a falsified or weakened antibiotic, the paper goes red, because the enzyme instead reacts with the nitrocefin. In short, yellow means good (appropriate strength antibiotic); red means bad (diluted antibiotic).

The device also includes a pH indicator, to determine if a sample is acidic or alkaline. This extra information could further alert the user to whether a sample has been falsified with filler ingredients, which might otherwise confound the main test.

It's simple, it's fast (about 15 minutes), and it can be used by an untrained professional - all key goals of the project, Henry said. Traditional approaches for testing drug purity rely on large, expensive analytical equipment in labs, including mass spectrometry, making it challenging or impossible for developing countries to access easily.

To ensure the usability of the device, the researchers included in their experiment a blind test with five users who were unfamiliar with the device or the science behind it. They all successfully identified 29 out of 32 antibiotic samples as either legitimate or false.

The test is effective for a broad spectrum of beta-lactam antibiotics, but there's room for refinement. The sample most misidentified by untrained users was acetylsalicylic acid -commonly known as aspirin - which did not turn as red as the other false samples because its acidic pH destabilized the reaction. Being able to more accurately distinguish such specific chemicals will be the subject of future optimization of the new test, the researchers say.

BINGHAMTON, N.Y. - CEOs who are paid less than their peers are four times more likely to engage in layoffs, according to research led by faculty at Binghamton University, State University of New York.

Scott Bentley, an assistant professor of strategy at Binghamton University's School of Management, worked on the research as a PhD student at Rutgers University. He and fellow researchers Rebecca Kehoe and Ingrid Fulmer, both associate professors at the Rutgers School of Management and Labor Relations, sought to find out if CEO pay was related to layoff announcements made by CEOs.

"In terms of strategic decisions that a CEO can make that could lead to higher pay, layoffs are one of the easiest to do," Bentley said. "Relative to other decisions such as mergers or acquisitions, layoffs typically don't need the approval of shareholders, the board or regulators, and they don't take years to do. Layoffs can be determined overnight."

Researchers analyzed data that included CEO pay and layoff announcements made by S&P 500 firms from 1992-2014 in the financial services, consumer staples and IT industries.

Adjusting the analysis for a number of different factors that could influence a layoff (industry conditions, company size, firm performance, etc.), researchers found that the "underpaid" CEOs were four times more likely to announce a layoff, even when all of those other factors were accounted for.

"In a way, CEOs are just like any other type of employee. They are going to compare their pay to those around them," Bentley said. "The difference is that the average employee can't make strategic decisions for the company that influences their own pay. Executives can."

Bentley says what surprised him most was that the relationship between lower pay and the likelihood of layoffs all but disappears when a CEO is paid more than his or her peers.

"Right around the point where CEOs are paid equal to their peers, the effect kind of goes away. We found that there's this huge dropoff in the likelihood of announcing layoffs once your pay is relatively the same as, or more than, your peers," he said.

So, do these actions actually pay off for the CEO? Well, it depends.

On average, researchers found CEO pay generally increased in the year following a layoff when firm performance also improved.

"While there are some instances where pay increased when performance decreased, we found that if the company and the shareholders don't benefit from the layoffs, neither does the CEO in most cases," Bentley said.

He said the findings highlight the importance of corporate governance and aligning the interests of the CEO with shareholders and employees.

"While we can't necessarily restrict a CEO's behavior or motivations, there may be ways to restrict the extent to which they are rewarded or impacted by decisions such as layoffs."

COLUMBUS, Ohio - The interaction of public and private debt in the United States reduced economic growth about 0.43 percentage points per year between 2009 and 2014, a new study suggests.

In addition, growth declined an additional 0.40 percent due solely to high levels of private debt, taking into account public debt.

Overall, the results suggest debt dragged U.S. growth down by at least 0.83 percentage points in this time period.

"The effect that debt is having on our economic growth is much larger than we expected. We were surprised," said Mehmet Caner, co-author of the study and professor of economics at The Ohio State University.

The nation's GDP (Gross Domestic Product) grew 4.1 percent in the most recent quarter, but Caner said growth would have been even larger without the current level of debt.

"We should be worried," he said.

Most economists have examined how one type of debt - either public or private - affects economic growth. But this study is one of the first to show that the interaction of the two should be a real concern, Caner said.

"We were able to quantify the effects of this debt interaction and it is kind of scary."

Caner and his colleagues used data from 29 advanced countries (members of the Organisation for Economic Co-operation and Development, or OECD) from 1995 to 2014 to see how debt was related to economic growth. They found that when both public and private debt were relatively low, their interaction could stimulate economic growth.

Even when debt rises, increases in public debt can be offset by decreases in private debt, or vice versa. But if they are both at relatively high levels and increasing at the same time, their interaction can be particularly harmful for growth, results showed.

The study found that the interaction of public and private debt reaches a "danger zone" when it goes above 100 and 137 percent of the nation's GDP for public and private debt respectively.

The researchers calculated that 12 of the 29 countries studied - including the United States - were in this danger zone during the time of the study. The U.S. public-private debt interaction was at 203 percent in the 2009-2014 period.

If debt was reducing U.S. growth by around 1 percentage point a year - as this study suggests - that may explain a large portion of why growth went from 3.3 percent per year before the Great Recession (2007-2009) to about 2.2 percent since the recession.

"Since 2014, both public and private debt ratios in the U.S. have increased, indicating that debt has become an even greater obstacle to growth," Caner said.

Not all kinds of private debt had the same effects, the study found. Results showed that household debt had a much more negative effect than corporate debt.

The reason may be that corporate debt generally goes to more productive uses compared to household spending, such as investments in plants and machinery.

Why is the interaction between private and public debt important for economic growth?

Caner said one reason might be that the government guarantees much private debt, including mortgages and school loans.

"Greater private default often means greater public debt," he said.

These results suggest that Congress should work to control public debt, as many commentators and political groups have suggested, Caner said.

"The other implication is that agencies responsible for regulating private debt should not ignore the interaction between public and private debt, especially mortgage debt," he said.

Aug. 21, 2018 -- In the future, your car windshield could become a giant camera sensing objects on the road. Or each window in a home could be turned into a security camera.

University of Utah electrical and computer engineers have discovered a way to create an optics-less camera in which a regular pane of glass or any see-through window can become the lens.

Their innovation was detailed in a research paper, "Computational Imaging Enables a 'See-Through' Lensless Camera," published in the newest issue of Optics Express. A copy of the paper, which was co-authored by University of Utah electrical and computer engineering graduate Ganghun Kim, can be downloaded here.

University of Utah electrical and computer engineering associate professor Rajesh Menon argues that all cameras were developed with the idea that humans look at and decipher the pictures. But what if, he asked, you could develop a camera that can be interpreted by a computer running an algorithm?

"Why don't we think from the ground up to design cameras that are optimized for machines and not humans. That's my philosophical point," he says.

If a normal digital camera sensor such as one for a mobile phone or an SLR camera is pointed at an object without a lens, it results in an image that looks like a pixelated blob. But within that blob is still enough digital information to detect the object if a computer program is properly trained to identify it. You simply create an algorithm to decode the image.

Through a series of experiments, Menon and his team of researchers took a picture of the University of Utah's "U" logo as well as video of an animated stick figure, both displayed on an LED light board. An inexpensive, off-the-shelf camera sensor was connected to the side of a plexiglass window, but pointed into the window while the light board was positioned in front of the pane at a 90-degree angle from the front of the sensor. The resulting image from the camera sensor, with help from a computer processor running the algorithm, is a low-resolution picture but definitely recognizable. The method also can produce full-motion video as well as color images, Menon says.

The process involves wrapping reflective tape around the edge of the window. Most of the light coming from the object in the picture passes through the glass, but just enough--about 1 percent--scatters through the window and into the camera sensor for the computer algorithm to decode the image.

While the resulting photo is not enough to win a Pulitzer Prize, it would be good enough for applications such as obstacle-avoidance sensors for autonomous cars. But Menon says more powerful camera sensors can produce higher-resolution images.

Applications for a lensless camera can be almost unlimited. Security cameras could be built into a home during construction by using the windows as lenses. It could be used in augmented-reality goggles to reduce their bulk. With current AR glasses, cameras have to be pointed at the user's eyes in order to track their positions, but with this technology they could be positioned on the sides of the lens to reduce size. A car windshield could have multiple cameras along the edges to capture more information. And the technology also could be used in retina or other biometric scanners, which typically have cameras pointed at the eye.

"It's not a one-size-fits-all solution, but it opens up an interesting way to think about imaging systems," Menon says.

From here, Menon and his team will further develop the system, including 3-D images, higher color resolution and photographing objects in regular household light. His current experiments involved taking pictures of self-illuminated images from the light board.

WASHINGTON -- Nearly six percent of urinary tract infections analyzed by a California emergency department were caused by drug-resistant bacteria in a one-year study period, according to new research in Annals of Emergency Medicine. The bacteria were resistant to most of the commonly used antibiotics. And, in many cases, patients had no identifiable risk for this kind of infection, the study found.

"The rise of drug-resistant infections is worrisome," said Bradley W. Frazee, MD, attending physician, Alameda Health System Highland Hospital and lead study author. "What's new is that in many of these resistant urinary tract infections, it may simply be impossible to identify which patients are at risk. Addressing the causes of antibiotic resistance, and developing novel drugs, is imperative. A society without working antibiotics would be like returning to preindustrial times, when a small injury or infection could easily become life-threatening."

The authors urge some immediate changes to clinical practice such as wider use of urine culture tests and a more reliable follow-up system for patients who turn out to have a resistant bug; improving emergency physician awareness of their hospital's antibiogram (a chart showing whether certain antibiotics work against certain bacteria); adherence to treatment guidelines and knowing which antibiotics to avoid in certain circumstances.

The Centers for Disease Control and Prevention (CDC) estimates that currently 23,000 Americans die each year from antibiotic-resistant infections.

The bacteria analyzed in this study were mostly E coli, that were resistant to cephalosporin antibiotics. Historically, such resistant bacteria were found in hospital-based infections. But, the authors note that they have been infecting more people outside of the hospital, particularly those with urinary tract infections. More than two in five (44%) of the infections analyzed were community-based (contracted outside of the hospital), the highest proportion reported in the United States to date.

Remember the scene in the movie Mission: Impossible when Tom Cruise has to sneak into the vault? He had to do all sorts of moves to avoid detection. That's what it's like to sneak a targeted drug into a kidney and keep it from getting eliminated from the body.

Since kidneys are the filtering agents in our body, they are keen to get rid of small particles that they sense do not belong. And if the kidney does not filter out a particle, excreting it through urine, it may be eliminated by the liver, which uses macrophages to search for and get rid of foreign bodies.

Researchers at the USC Viterbi School of Engineering, along with colleagues from the Keck School of Medicine at USC, have engineered peptide nanoparticles to outsmart the biological system and target the kidney cells. The innovation may prove critical to addressing chronic kidney disease.

One out of three Americans will have chronic kidney disease in their lifetime. To date, there have been few solutions for advanced kidney disease beyond dialysis and kidney transplant--both of which are incredibly expensive and taxing. Previously, doctors would also have to prescribe heavy doses of medication as they hoped some of the medication would be able to reach and target the kidney. However, this heavy dosing had adverse effects on other organs in the body.

While targeted drug delivery has long been an area of concentration for cancer research, nanoparticles for targeted drug delivery for the kidneys has largely gone unexplored, says the study's lead author, Eun Ji Chung, a WiSE Gabilan Assistant Professor and Assistant Professor of Biomedical Engineering, Chemical Engineering and Materials Science, and Nephrology and Hypertension at USC and a professor in the new USC Michelson Center for Convergent Bioscience.

Essentially, the researchers took several months to create their kidney targeting particle. This nanoparticle is a micelle, which is 10-20 times smaller than a traditional nanoparticle. This particular micelle is synthesized from a peptide chain that is formulated from lysine and glutamic acids. The extra small size of the nanoparticle allows passage into the kidneys through the initial barrier of kidney filtration while the peptide allows the nanoparticle to stay in the kidneys and potentially unload a drug at the site of the disease without getting removed by the urine. In this way, the researchers are taking advantage of a natural mechanism of the body to target the kidneys, and can minimize systemic off-target side effects that are characteristic to most kidney drugs.

Results of In Vivo Testing:

The researchers injected mice with fluorescent-labeled nanoparticles. They found that the nanoparticles they had engineered were more present in the kidney than other parts of the body. These particles thus could carry drugs more selectively than previous tests by other researchers. Furthermore, these biocompatible, bio-degradable particles were able to clear out of the body in less than one week and would not damage other organs.

The study "Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery," was conducted by Eun Ji Chung, Jonathan Wang, Christopher Poon, Deborah Chin, Sarah Milkowski, Vivian Lu at the Viterbi School of Engineering; and Kenneth R. Hallows of the Keck School of Medicine at USC. It was featured in the journal Nano Research and Professor Chung was selected as a Young Innovator in Nanobiotechnology from the journal.

Funding for this research came from the University of Southern California (Provost Fellowship), the National Heart, Lung, and Blood Institute at the NIH, and the U.S. Department of Defense.

Lugano, Switzerland- 21 August 2018 - A new scale for tumour DNA mutations which will simplify and standardise choices for targeted cancer treatment has been agreed by leading cancer specialists in Europe and North America. The scale, called ESCAT (ESMO Scale for Clinical Actionability of molecular Targets), is published this week in the Annals of Oncology (1). It aims to optimise patient care by making it easier to identify patients with cancer who are likely to respond to precision medicines, and help make treatment more cost effective.

"Doctors receive a growing amount of information about the genetic make-up of each patient's cancer, but this can be difficult to interpret for making optimal treatment choices," explains Professor Fabrice André, Chair of the ESMO Translational Research and Precision Medicine Working Group (2) who initiated this project. "The new scale will help us distinguish between alterations in tumour DNA that are important for decisions about targeted medicines or access to clinical trials, and those which aren't relevant."

The new grading system classes alterations in tumour DNA according to their relevance as markers for selecting patients for targeted treatment, based on the strength of clinical evidence supporting them (Tier I-V, Table 1). It is the first time that a classification has been developed that is relevant to all potential targeted cancer medicines, not just those that have been approved for use by national regulatory bodies. The classification also enables mutations to be upgraded or downgraded in response to newly available data.

"For the first time, ESMO has created the tools to make it clear what data are needed for a mutation to be considered actionable and how this may change in response to new clinical data," says Dr Joaquin Mateo, lead author of the paper, Principal Investigator of the Prostate Cancer Translational Research Group from the Vall d'Hebron Institute of Oncology, Barcelona, Spain.

"The scale focuses on the clinical evidence for matching tumour mutations with the drugs we have in our clinics and gives us a common vocabulary for communication between clinicians, and for explaining potential treatment benefits to patients," he continues.

As ESMO disseminates ESCAT into clinical practice, it is hoped that cancer centres and laboratories will start to routinely include Tier I-V grading of genomic mutations in patients' clinical and laboratory reports and discuss results at tumour boards and clinics.

"If one mutation is Tier I and another is Tier III, it is important that everyone understands the need to prioritise the Tier I mutation in determining the patient's treatment and implementing precision medicine," Mateo points out.

ESCAT will also make it easier for clinicians and patients to discuss the results of multigene sequencing. More and more patients are offered a multigene sequencing nowadays. Current testing techniques frequently show that many of the genes in a patient's tumour are mutated but it is unclear which are relevant to treatment decisions. By using the scale to show which alterations are relevant, it becomes easier to identify and agree the right treatment for the right patient.

"ESCAT will bring order to the current jungle of mutation analysis so that we all speak the same language for classifying mutations and prioritising how we use them to enhance patient care," concludes André.

The study is the largest of its kind worldwide and examined data on more than one million hospital admissions wholly attributable to alcohol over 12 years.

Areas with a high density of alcohol outlets have higher drink-related hospital admission rates, a new study from the University of Sheffield has found.

The study, conducted by researchers from the University's School of Health and Related Research (ScHARR), revealed that the places in England with the most pubs, bars and nightclubs had a 13 per cent higher admission rate for acute conditions caused by alcohol such as drunkenness and vomiting.

These areas also had a 22 per cent higher hospital admission rate for chronic conditions caused by alcohol - such as liver disease, compared with places with the lowest density of alcohol vendors.

The research, funded by Alcohol Research UK, analysed both on-trade outlets - where alcohol can be bought and consumed on the premises such as pubs, clubs and restaurants - as well as off-trade outlets - where alcohol is purchased to drink elsewhere, like supermarkets and convenience stores.

The study, which is the largest of its kind worldwide, examined data on more than one million admissions wholly attributable to alcohol over 12 years. It included all 32,482 census areas in England.

The results also showed:

Places with the highest density of restaurants licenced to sell alcohol had nine per cent higher admission rates for acute conditions and nine per cent higher admission rates for chronic conditions caused by alcohol.

Areas with the highest density of other on-trade outlets (such as hotels, casinos and sports clubs) had 12 per cent higher admission rates for acute conditions and 19 per cent higher admission rates for chronic conditions caused by alcohol, compared with areas with the lowest density of other on-trade outlets.

Places with the highest density of convenience stores had 10 per cent higher admission rates for acute conditions and seven per cent higher admission rates for chronic conditions compared with areas with the lowest density of convenience stores.

Ravi Maheswaran, Professor of Epidemiology and Public Health at the University of Sheffield, said: "The strongest link was between pubs, bars and nightclubs and admissions for alcoholic liver disease.

"We also observed an association between restaurants licenced to sell alcohol and hospital admissions, which we had not expected. This needs further investigation to establish if there is a causal link.

"While convenience stores were clearly associated with hospital admissions, the association for supermarkets was modest, as we had expected. Supermarkets account for a significant proportion of alcohol sales, however they tend to serve large catchment areas whilst our study was set up to examine the effects of outlet density in small local areas."

Outlet density was measured as the number of alcohol retail outlets within a 1km radius of the centre of every residential postcode in England. This was classified into four categories, ranging from lowest to highest and the analysis adjusted for other factors which could have influenced associations, including differences in age, socio-economic deprivation and hospital admission policies in different areas.

Professor Maheswaran added: "Although we have observed clear associations between alcohol outlet densities and hospital admissions, our study cannot confirm if these associations are causally linked.

"However, there is emerging evidence from other studies suggesting that local licencing enforcement could reduce alcohol related harms."

The research was funded by Alcohol Research UK, an independent charity working to reduce alcohol-related harm through ensuring policy and practice can be developed on the basis of reliable, research-based evidence.

Dr James Nicholls, Director of Research and Policy Development at Alcohol Research UK said: "Understanding the relationship between outlet density and alcohol hospital admissions is essential to reducing harm. Local licensing authorities, in particular, need to factor this information into their decisions.

"We often hear that no individual outlet can be held responsible for increased hospital admissions, and because of this licensing teams can't plan on that basis. However, this study adds weight to the argument that licensing needs to also think about the overall level of availability in a given area.

"As the evidence on the relationship between availability and harm becomes stronger, those tasked with regulating the market need to respond."

Previous work by the University of Sheffield researchers showed a vast increase in the number of off-trade outlets, such as convenience stores and supermarkets that sell alcohol. The amount of convenience stores selling alcohol more than doubled from 2003 to 2013, with an increase of 104 per cent. The number of supermarkets selling alcohol also increased by 33 per cent.

SAN FRANCISCO--August 20, 2018--To fight viral infections, your immune system calls on CD8 T cells to kill the infected cells. The CD8 T cells can also be used in immunotherapy approaches to kill cancer cells, including the CAR T cell therapy currently attracting broad public attention.

"The problem is that CD8 T cells are often exhausted in cancer and chronic infections like HIV, so they die off or stop functioning properly," said Shomyseh Sanjabi, PhD, an assistant investigator at the Gladstone Institutes who has been studying this cell type for nearly 15 years. "I've been trying to better understand how these cells develop in order to find ways to help them regain their function and live longer."

When you initially get exposed to an invading pathogen, such as a virus, CD8 T cells begin to rapidly multiply. At this stage, they are called effector cells and act like foot soldiers, killing infected cells. Once the pathogen is gone, most effector cells die to ensure they don't begin to attack your own body.

The ones that survive become memory cells, which are more like specialized guards, patrolling your body for the same invaders for the rest of your life. The next time you get exposed to the same pathogen, these memory cells allow your body to respond much more quickly and protect you.

In a new study published in the scientific journal PNAS, Sanjabi and her team identified two molecules, Sprouty 1 and Sprouty 2, that modify the survival of effector T cells and the development of memory CD8 T cells. Their findings offer promising potential for immunotherapeutic strategies to combat cancer and chronic infections.

Better Without Sprouty

Using animal models that Sanjabi has been developing for the past 10 years, the researchers in her laboratory deleted both Sprouty 1 and Sprouty 2 from CD8 T cells to see what would happen.

They found that a larger than usual number of effector cells survive and become memory cells. The team also showed that the resulting memory cells, which lack the Sprouty molecules, actually have better protective capacity against a bacterial pathogen than regular memory cells.

They also showed these same memory cells consume less glucose (sugar) as an energy source than normal CD8 T cells. While effector cells depend on glucose to live, memory cells generally use more fatty acids.

"Tumor cells use a lot of glucose, so effector cells have difficulty surviving in the tumor environment because it doesn't have a sufficient source of energy," explained Hesham Shehata, PhD, former postdoctoral scholar in Sanjabi's laboratory and first author of the study. "While memory cells generally don't depend on glucose, our study suggests that effector cells without Sprouty 1 and 2 consume less glucose, so they could survive and function in a tumor environment much better."

Memory Is Good for Immunotherapy

Sanjabi's study offers a new way to increase the number, survival, and function of memory CD8 T cells, which could provide better protection against tumors and pathogenic infections.

"By shedding light on the role of Sprouty 1 and 2, our work revealed another layer of the underlying biology of T cells," said Shehata. "Cells that lack Sprouty 1 and 2 have immense potential not only to fight tumors, but chronic viral infections as well. It's exciting that our study can be applied to multiple contexts."

In the case of HIV, for instance, deleting the two Sprouty molecules could lead to memory cells that better survive and could effectively kill the activated cells harboring latent virus, one of the main barriers to a cure.

As for cancer immunotherapy, recent studies have shown that approaches using memory cells can help reduce tumor sizes or even completely eliminate tumors, as compared to treatments using effector cells that have led to more patients relapsing.

"There's been great interest within the scientific community to enhance the development and function of memory CD8 T cells, which work better for immunotherapies than effector T cells," said Sanjabi, who is also an associate professor of microbiology and immunology at UC San Francisco. "Our findings could provide an opportunity to improve future engineering of CAR T cells against tumors. This could potentially be used in combination with a genome editing technique like CRISPR that would remove the Sprouty 1 and 2 molecules from the cells to make them more effective."