Culture

CHICAGO (April 28, 2020): Amid shortages of personal protective equipment due to the Coronavirus Disease 2019 (COVID-19) pandemic, a St. Louis health care system has implemented a process to disinfect disposable N95 respirator masks that allows health care workers to reuse their own mask for up to 20 cycles. The novel disinfection process, developed in collaboration with Washington University School of Medicine, uses vaporized hydrogen peroxide and is described in an "article in press" on the Journal of the American College of Surgeons website in advance of print.

Test results from a pilot program at Barnes-Jewish Hospital and two other hospitals that are also part of BJC HealthCare, showed that the disinfection process kills germs from N95 masks while ensuring that the only person who touches the mask is the original mask wearer, study authors reported.

"Our primary outcome is safety for the health care worker," said project leader and study coauthor Andrew Pierce, MHSA, director of supply plus at Barnes-Jewish. "We want to make it safer for team members who are at risk while taking care of patients with a known or possible COVID-19 diagnosis."

Their program uses a disinfecting procedure first tested by Duke University researchers in 2016.1 However, the Barnes-Jewish process has a unique modification--an identification system that enables the hospital to return the sanitized mask to the same individual each time, said senior author Shaina Eckhouse, MD, FACS, assistant professor of surgery at Washington University School of Medicine, St. Louis. Dr. Eckhouse is part of the multidisciplinary team of university and hospital staff who developed the disinfection program.

This approach, according to the authors, increased employee acceptance of reusing what is normally a single-use N95 mask and helped ensure proper fit of the returned mask.

During the COVID-19 pandemic, the Centers for Disease Control and Prevention has recommended strategies for conserving personal protective equipment, including decontamination and reuse of N95 masks.2 Almost half of U.S. health care facilities reported being nearly or completely out of N95 respirator masks, according to a March 27 survey conducted by the Association for Professionals in Infection Control and Epidemiology.3

In late March, before the program began, Barnes-Jewish had a low inventory of N95 masks--about a week's worth--and no expectations for replenishment because of international shortages in hospital supply chains, according to Mr. Pierce.

How the process works

The disinfection process that has since been put into place begins at the end of a shift. A health care provider removes his or her N95 mask in that unit's soiled utility room and places it in a sterilization pouch (Crosstex) made of breathable polyethylene fiber (Tyvek by DuPont) on one side. On the other side of the sealed pouch, the worker writes his or her name or employee ID number, hospital, department, and unit location and puts the pouch in the soiled collection bin.

A designated worker wearing proper protection collects the bins twice a day and takes them to a specially designed and sealed disinfection room--built in four days, according to Dr. Eckhouse. There the pouches are arranged, breathable side up, by clinical unit on wire racks. A hydrogen peroxide vapor generator (Bioquell Z-2), which Washington University already owned to decontaminate equipment, fills the room with the chemical.

After 4.5 hours of disinfection, a worker moves the racks of masks to another area that has a fan to offgas the hydrogen peroxide, where the masks stay until sensors record a zero reading. The pouches are returned to their respective units in a decontaminated bin, finishing a process that takes about seven hours, Mr. Pierce said.

Workers can wear their mask up to three weeks because past studies show that disinfection more than 20 times could alter the fit of the mask, he noted.

Since the program began April 1 in the Barnes-Jewish emergency department, it expanded in just two weeks to additional clinical departments and other hospitals in the system, which Mr. Pierce called "an immense achievement."

"A welcome improvement"

Currently, Mr. Pierce said they are disinfecting 240 N95 masks a day and have the capability of disinfecting 1,500 masks daily.

Without the disinfection program, he said the health care system would need to discard a substantial amount of its respirator masks. Because of the disinfection, the hospitals now have enough masks to last for weeks.

"This program is a welcome improvement for extended usage of N95s during the shortage that we are facing," Mr. Pierce said.

Dr. Eckhouse said other hospitals facing mask shortages can reproduce the disinfection program if they bring together experts in environmental health and safety, medicine, and facility management. "Having the infrastructure already in place would improve the ease of deploying an N95 disinfection process," she stated.

CINCINNATI - By leveraging the basics of artificial intelligence technology now used to predict risk for suicide or other mental health issues, researchers developed an AI system that analyzes linguistic patterns to predict a youth's risk for committing acts of school violence.

Study data published in the International Journal of Medical Informatics by physicians and clinical informaticians at Cincinnati Children's Hospital Medical Center show the system can detect the risk of aggression for individual subjects.

The AI system uses pattern-recognizing machine learning and natural language processing (NLP) technologies. It combines the analytical scope and speed of information technology with clinical risk-assessment data and practitioner expertise, thereby automating a complex and time-consuming process, according to Yizhao Ni, PhD, co-principal investigator and a clinical informatician in the Division of Biomedical Informatics.

The technology uncovered multiple warning signs that could deliver useful clinical insights to assist personalized interventions, Ni explained. When fully developed, the system's built-in risk assessment scales and automated risk prediction algorithms should produce an accurate and scalable computerized screening service to prevent school violence.

"Students are physically or verbally bullied on school property, electronically through texting or social media, and youth violence costs society billions of dollars in health care expenses or lost productivity," Ni said, citing data from the U.S. Centers for Disease Control and Prevention.

"Our study demonstrates that overall, our AI system matches the clinical judgements and accuracy of psychiatrists 94 percent of the time. It has tremendous potential to help address youth violence at school and eventually other mental health conditions."

Empowering a Solution

Earlier research shows that using NLP and machine learning technologies pioneered at Cincinnati Children's and elsewhere improve risk prediction for mental health problems like suicide. Current study authors note that so far there are no automated solutions developed to predict the risk for violent behaviors at school.

Recent advancements in school-based crime prevention programs demonstrate the best results occur when at-risk youth receive timely and individualized intervention, according to Drew Barzman, MD, co-principal investigator and director of the Child and Adolescent Forensic Psychiatry Service at Cincinnati Children's.

But high patient need and busy clinical schedules can constrain the ability to complete the complex, labor intensive tasks needed for timely clinical evaluation of mental health patients. An effective automated system could help overcome this challenge and help mental health caregivers deliver timely interventions based on a youth's individual needs, he said.

Study Design

The study was tested by embedding it as a clinical service in the Division of Child and Adolescent Psychiatry at Cincinnati Children's. The division's inpatient units receive about 30,000 psychiatric admissions annually. Its outpatient clinic has over 52,000 patient visits every year.

Conducted between May 2015 and April 2018, the study prospectively recruited 131 students between ages 10 and 18 years from middle and high schools in Ohio, Kentucky, Indiana, and Tennessee.

Clinical assessments by psychiatrists indicated that 68 students (52 percent) were considered high risk towards others. For analysis with the AI assessment tool, the patients were segmented into smaller groups to compare the system's predictive reliability when compared physician-generated patient clinical assessments. These comparisons yielded the AI system's overall risk assessment match rate of 94 percent.

Future development plans for the tool include seeking research collaborations with other medical institutions and school systems to test live implementation in educational and medical settings, according to the researchers. Researchers said that based on funding capabilities, this will be the next phase of their work.

DALLAS, April 28, 2020 -- Upward income mobility is associated with a trade-off between well-being and cardiometabolic health, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association. The article appears in a special spotlight issue exploring different aspects of the complex relationships between psychosocial factors and cardiovascular health.

To study cardiometabolic health, the research focused on metabolic syndrome, which is a collection of signs that predispose individuals to later diabetes, stroke and heart attack. These signs include abdominal fat, high blood pressure, elevated cholesterol levels and high blood glucose.

Researchers from Northwestern University and the University of Georgia analyzed data from two multi-decade studies: 7,542 participants in the National Longitudinal Study of Adolescent Health and 1,877 participants in the Midlife in the United States Study. The participants entered the studies as youth and were followed into adulthood. They grouped participants into one of four categories based on their family income during childhood and adulthood: those who were consistently advantaged or consistently disadvantaged, and those who experienced upward or downward mobility (meaning higher or lower income in adulthood relative to childhood).

Researchers' key conclusions:

Upwardly mobile participants reported substantially less psychological distress than consistently disadvantaged individuals. In fact, in most comparisons their distress levels were comparable to consistently advantaged participants.

However, this pattern was reversed for metabolic syndrome: upwardly mobile participants fared worse than those with consistent advantage and closely resembled individuals with consistent disadvantage.

Because high socioeconomic status is associated with fewer health problems, it is commonly believed that as people's financial conditions improve, so will their health. However, these results suggest upward mobility entails a trade-off, where improving financial conditions forecast higher psychological well-being, but worse cardiometabolic health.

Upward mobility is not always beneficial for cardiometabolic health, even if it improves economic standing and mental health.

Study coauthors, disclosures and funding sources are detailed in the manuscript.

New research, published online today in the American Journal of Psychiatry, finds that children's rearing environment has a meaningful impact on their risk for major depression later in life, and notes the importance supporting of nurturing environments when children are at risk. In the study, authors analyzed the health records of full and half siblings with at least one biological parent with depression who were raised by either their biological parents or in carefully screened adoptive homes. Generally, the children in adopted homes showed lower risk, but whatever the setting, episodes of major depression in the parents meant the children were more susceptible to depression themselves.

"The Rearing Environment and Risk for Major Depression: A Swedish National High-Risk Home-Reared and Adopted-Away Co-Sibling Control Study"--led by Kenneth S. Kendler, M.D., with Virginia Commonwealth University in Richmond, and Kristina Sundquist, M.D., Ph.D., from Lund University in Malmö, Sweden--involved data from the Swedish National Sample. The researchers identified 666 high-risk full sibling pairs and 2,596 high-risk pairs of half siblings each with at least one child reared at home and one adopted. High risk was defined as having at least one biological parent with major depression. In Sweden, the adoptive parents are carefully screened and undergo a rigorous selection process to ensure their ability to "provide a supportive and generally advantaged home for their adoptive child."

In the full sibling group, the risk for major depression among adopted siblings was 23% lower than the sibling raised in the home with their birth family. In the group of half siblings, the risk of depression was 19% lower for the adopted siblings. For both the full and half sibling groups, the protective effect of adoption disappeared when an adoptive parent or step-sibling had major depression or when the

The study authors conclude that their results "further strengthen the evidence that high-quality rearing environments can meaningfully reduce rates of major depression in individuals at high familial risk." The research also "supports efforts to improve the rearing environment in high-risk families as an approach to the primary prevention of major depression," the authors note.

Myrna M. Weissman, Ph.D., from Columbia University Vagelos College of Physicians and Surgeons, noted in her accompanying commentary that to the question of whether it is nature or nurture that contributes to depression risk, the answer remains "yes," it is nature and nurture, with relative proportions and for which type of depression continuing to be examined. Yet, for the present study "the results demonstrate the strong impact of the rearing environment on risk for major depression and support the importance of intervention efforts to improve the rearing environment in high risk families."

In an exploratory study of nearly 10,000 women with no history of cancer, researchers evaluating a multi-cancer blood test report that it successfully detected some cancers, including early cancers that could be localized and surgically removed. Among the cancers detected were ovarian cancers, which are typically diagnosed at an advanced stage. Important to the authors' focus on safety and feasibility, the test could be done without incurring a large number of futile, invasive follow-up tests and without discouraging the participants from engaging in other forms of standard cancer screening such as mammography. Even as further trials will be needed, the study was able to address several fundamental issues about multi-cancer blood tests, the authors say. Diagnosing cancers earlier is one of the keys to reducing future cancer deaths. Presently, screening approaches decrease mortality from colon, breast, lung, and cervical cancers, but adherence varies widely, and some forms of cancer screening are not recommended for average-risk individuals. A minimally invasive, multi-cancer screening test could increase cancer detection rates when applied to a population already following standard screening approaches. Several questions remain about multi-cancer blood-based screening tests, however. In their new study, DETECT-A (Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing), Anne Marie Lennon and colleagues attempted to answer several of these questions, including whether these tests can detect cancer in individuals whose cancer was not previously detected by other means. Lennon and colleagues recruited nearly 10,000 women 65 to 75 years of age with no history of cancer. Their analysis looked for nearly all cancer types, based on circulating DNA and protein biomarkers of cancer. To maximize safety, DETECT-A incorporated three steps prior to initiating a diagnostic work-up for cancer. Only in the third step, if no non-cancer-related cause for an abnormal result was found, were individuals with a positive test invited to undergo the final component of testing - a full-body diagnostic positron emission tomography-computed tomography (PET-CT) scan. This test is routinely used in clinical practice to aid in detecting, localizing, and diagnosing tumors.
The blood test used in the DETECT-A study was an early version of a multi-analyte test called CancerSEEK (http://science.sciencemag.org/cgi/doi/10.1126/science.aar3247) and it ultimately found cancer in 26 women. Other cancers not detected by the blood test were also found in the study participants. In total, 96 cancers were diagnosed during the 12-month study. Of these, 26 were detected by the blood test, 24 by standard screening, and 46 by other means. An analysis of whether participants in the study had fewer mammograms after the baseline blood test than they had in the years prior showed they did not greatly change their habits, suggesting that such a test can be incorporated into routine clinical care and not discourage participants from engaging in standard-of-care screening, which the authors emphasize their approach shouldn't replace. They note that DETECT-A was not designed for regulatory approval of a specific test. Larger trials, including formal registration trials, will be necessary to further evaluate the clinical validity and utility of such testing, they say.

BINGHAMTON, NY -- Go ahead: Give your partner a hug or cuddle while you catch some Netflix. According to recently published research from Binghamton University, State University of New York, it just might build a stronger relationship.

The study, led by Binghamton University doctoral student in psychology Samantha Wagner, particularly looks at the effects of non-sexual intimate touch -- for example, hugging, holding hands or cuddling on the couch, rather than actions intended to lead to sex. Attachment style refers to human social bonds and exists on a spectrum; avoidant individuals prefer more interpersonal distance, while anxious individuals seek greater closeness. This style develops in childhood, but can change over time and vary with the individual in question.

"It all depends on how open, close and secure you feel with that person, which is impacted by many, many factors," Wagner said.

To determine the connection of attachment style, touch satisfaction and marital satisfaction, researchers used a sample of 184 couples over the age of 18, consisting of husbands and wives; same-sex couples were excluded. Because the study protocol included hormonal sampling, individuals on hormonal therapy were also excluded, as well as postmenopausal, pregnant or breastfeeding women. They were interviewed separately on their attachment tendencies, the amount of touch and routine affection in their relationships, and their relationship satisfaction.

Researchers expected to find that avoidant individuals preferred less touch, while anxious people prefer more. What they found was more nuanced.

The more routine affection that couples experienced, the more they felt satisfied with their partners' touch, even if they had avoidant attachment styles. With low levels of physical affection, anxious husbands were less satisfied with the touch they received, but not anxious wives, who may instead choose to solicit the missing affection.

For men, higher levels of routine affection are associated with relationship satisfaction; in other words, touch is a positive, the icing on the marriage cake. For women, lower levels of routine affection correlated with relationship dissatisfaction, meaning that touch is an essential ingredient and its absence is a negative. It's a subtle distinction.

"There's something specific about touch satisfaction that interplays with relationship satisfaction but not dissatisfaction for wives," said Wagner, who noted that further research studies may be able to clarify the distinction.

Whatever a couple's attachment insecurities, the perception of how their partner touches them has the greatest association with "touch satisfaction." In other words, more is better because they can more easily see that their partner is trying to engage with them.

Overall, the study shows an association between non-sexual physical affection and solid marriages, although the current data can't establish cause and effect.

"Interestingly, there's some evidence that holding your partner's hand while you're arguing de-escalates the argument and makes it more productive," said Wagner, who has used the technique with clients.

However, Wagner emphasized that the study focused only on healthy, consensual touch -- not manipulation or abuse. Touch holds different meanings for people, she pointed out; someone with autism spectrum disorder may be overwhelmed by tactile sensitivity, and someone with a history of trauma may experience touch as averse.

Wagner is, by her own admission, a hugger and has long been fascinated by the healing possibilities of touch; she wrote her senior thesis as a qualitative review of the uses and benefit of touch across the lifespan. But questions continued to arise: Why do some people enjoy touch more than others? And do they benefit more as a result?

As the coronavirus pandemic continues, couples may want to consider adding more affection to decrease stress -- as long as their partners are receptive and willing.

"Feel free to give some extra snugs on the couch. There's plenty of evidence that suggests touch as a way to decrease stress," she said.

But she notes that the coronavirus pandemic also may lead to touch deprivation, as social distancing keeps us physically apart from one another. Consider, for example, healthcare workers who are quarantining themselves from their own families when they return home, to keep the virus from spreading to their loved ones.

"I think we should all hold the loved ones we can a little closer and be thoughtful of the struggles that others might be having because they can't do just that," she said. "If anything is true for me, a hug has become even more precious than it was before."

Most treatment providers for individuals with alcohol use disorders are well versed in either the 12-Step Alcoholics Anonymous program or in a different treatment such as cognitive behavioral therapy -- but the two approaches can mesh well, according to a Baylor University researcher.

Alcohol use disorders are among the most common psychological disorders experienced by Americans, according to the National Institute on Alcohol Abuse and Alcoholism. Only an estimated 10 percent of those with disorders receive treatment, with the most popular treatment being some form of Alcoholics Anonymous 12-Step involvement. But many misconceptions about AA continue to exist.

"Clinicians should be mindful if they have biases or misconceptions about the AA program and AA members, and empirical research on how well 12-Step programs work is now widely available," said Sara Dolan, Ph. D., associate professor of psychology and neuroscience and director of the doctor of clinical psychology (Psy.D.) graduate program at Baylor University. "Because it is likely that clinicians will work with people who engage in 12-Step programs, we should learn as much as we can about how to integrate 12-Step treatment into our work with these clients."

The article -- "Treatment of Alcohol use disorder: Integration of Alcoholics Anonymous and cognitive behavioral therapy" -- is published in the American Psychological Association journal Training and Education in Professional Psychology.

Authors discussed misconceptions about AA, including these beliefs:

That AA is a religious program requiring belief in God to work the steps. While a historic Christian influence exists in AA's principles (self-examination, confession, restitution and service to others), AA considers itself a "spiritual program of action." It is not allied with any sect, denomination, politics, organization or institution, and it does not endorse or support causes. The Big Book -- AA's recovery manual -- asks only whether one is "even willing to believe that there is a Power greater than myself," with no requirement to define this Power or state with absolute certainty it exists.

That AA negates personal responsibility for sobriety. Although the First Step of the program asks individuals to admit "powerlessness" over alcohol, the program aims to help individuals accept personal responsibility for their actions.

Some important distinctions do exist between AA and cognitive behavioral therapy (CBT), Dolan said. While AA's goal is total abstinence, CBT sometimes encourages total abstinence and sometimes seeks to reduce the amount one drinks to reduce harm to self or others. Another difference is that in AA, the primary therapeutic relationship is with a peer -- someone who is in recovery from harmful alcohol and substance use. In CBT, the primary relationship is with a psychotherapist who may or may not be in recovery. Yet another difference is that in AA or 12-step programs, clients can get free help that protects their anonymity.

But the two approaches have much in common, Dolan said. In both, the work that is done to achieve control over drinking is fundamentally cognitive-behavioral in nature.

For example, AA strives to identify the thoughts, emotions, attitudes and behaviors that cause problems, then replace them with new, more adaptive ones to overcome problematic alcohol and other drug use and to engage in altruistic behavior.

Similarly, cognitive behavioral therapy seeks to identify and replace dysfunctional beliefs and help clients learn to cope through means other than drinking, Dolan said.

AA and cognitive behavioral therapy have similar definitions of alcohol and substance use disorder and are alike in that they urge individuals to take stock of emotions and behaviors -- CBT through a daily thought record of negative emotions and AA through daily admittance of selfish, dishonest, self-seeking or fearful thoughts or behaviors.

Some interventions and skills also are similar. CBT promotes social support, interpersonal skills training and learning to regulate emotion and tolerate distress; AA advocates avoiding former "people, places and things" conducive to drinking, instead using sponsors and support groups and modeling the behavior of sober AA members.

Both approaches advocate taking responsibility for one's actions, acceptance and times of self-examination and relaxation, researchers wrote. CBT advises using relaxation techniques and training, while AA suggests prayer and meditation.

The article recommends that clinicians be aware of their misconceptions about AA and AA members and educate themselves about AA. For example, attendance as a guest at AA meetings (some are open to guests, while others are members only) would be helpful, as well as reading AA's program material, including the Big Book.

In addition, the authors suggest that efforts to "translate" 12-Step language into the terminology of cognitive behavioral therapy may help clinical trainees understand the corollaries between the two approaches and bridge the gap.

Rutgers engineers have created a highly effective way to paint complex 3D-printed objects, such as lightweight frames for aircraft and biomedical stents, that could save manufacturers time and money and provide new opportunities to create "smart skins" for printed parts.

The findings are published in the journal ACS Applied Materials & Interfaces.

Conventional sprays and brushes can't reach all nooks and crannies in complex 3D-printed objects, but the new technique coats any exposed surface and fosters rapid prototyping.

"Our technique is a more efficient way to coat not only conventional objects, but even hydrogel soft robots, and our coatings are robust enough to survive complete immersion in water and repeated swelling and de-swelling by humidity," said senior author Jonathan P. Singer, an assistant professor in the Department of Mechanical and Aerospace Engineering in the School of Engineering at Rutgers University-New Brunswick.

The engineers discovered new capabilities of a technology that creates a fine spray of droplets by applying a voltage to fluid flowing through a nozzle. This technique (electrospray deposition) has been used mainly for analytical chemistry. But in recent decades, it has also been used in lab-scale demonstrations of coatings that deliver vaccines, light-absorbing layers of solar cells and fluorescent quantum dots (tiny particles) for LED displays.

Using their approach, Rutgers engineers are building an accessory for 3D printers that will, for the first time, allow automated coating of 3D-printed parts with functional, protective or aesthetic layers of paint. Their technique features much thinner and better-targeted paint application, using significantly fewer materials than traditional methods. That means engineers can use cutting-edge materials, such as nanoparticles and bioactive ingredients, that would otherwise be too costly in paints, according to Singer.

Next steps include creating surfaces that can change their properties or trigger chemical reactions to create paints that can sense their environment and report stimuli to onboard electronics. The engineers hope to commercialize their technique and create a new paradigm of rapid coating immediately after printing that complements 3D printing.

A new study warns mobile phones could be acting as 'Trojan horses' for coronavirus and urges billions of users worldwide to decontaminate their devices daily.

The research, led by Associate Professor Lotti Tajouri of Bond University, reviewed 56 studies from 24 countries and found phones host a staggering cocktail of live germs.

While all the studies predate the current pandemic, the authors say the virus responsible for COVID-19 -- SARS-CoV-2 -- is probably present on mobile phones and other touch-screen devices of coronavirus sufferers.

"Our recommendation is that phones should be decontaminated daily and regularly with either 70 per cent isopropyl or by sanitising with (ultraviolet) devices like PhoneSoap," the study says.

The systematic review found golden staph and E. Coli microbes were among the most common bugs on phones.

Dr Tajouri, a biomedical scientist, said mobile devices were 'five-star hotels with premium heated spas, free buffet for microbes to thrive on'.

"They have temperature control, we keep them in our pockets, we are addicted to them," he said.

"We talk into them and deposit droplets that can be full of viruses, bacteria -- you name it.

"We eat with them, so we give nutrients to micro-organisms.

"And nobody -- absolutely nobody - washes or decontaminates their phone."

He said people travelled with their phones "and no border officers check them. It surely causes a biosecurity concern.

"That's why mobile phones are Trojan horses. We don't know that we are carrying the enemy."

Dr Tajouri said phone super-users touched their devices up to 5000 times a day and even the average user handled them an average of three hours a day.

"We know from the Centers for Disease Control and Prevention (CDC) that 80 per cent of all infections are associated with our hands.

"You can wash your hands as many times as you like -- and you should -- but if you then touch a contaminated phone you are contaminating yourself all over again.

Think of your phone as your third hand."

Community transmission could occur when an infected person touched their phone and then a pole on a bus which was grasped by an elderly person, he said.

"The extraordinarily fast contagion that has scientists puzzled might reside within these mobile phones spreading COVID-19 everywhere at ultra-speed," Dr Tajouri said.

"After all, they're everywhere, travelling the world in planes, cruise ships and trains.

"Let's take that hypothesis seriously. If we clean our phones daily and this makes a difference then we might with this little action curve down the COVID-19 epidemic and save lives."

But Dr Tajouri said more research was needed to determine the role contaminated phones were playing in the coronavirus pandemic.

Poultry geneticists have long studied the inheritance of a prized fancy chicken breeding trait; feathered legs.

Lead researcher Leif Andersson and colleagues at Texas A&M University, have investigated the genetic basis of foot feathering. The trait, known scientifically as ptilopody, can be observed in domesticated and wild avian species and is characterized by the partial or complete development of feathers on the skin of the ankles and feet.

"Foot feathering is an interesting case since, although it is a very recognizable trait that can be very easily selected to fixation in breeds, it is in fact not a monogenic trait, caused by a single gene," said Andersson.

In previous studies, two independent dominant alleles, denoted Pti-1 and Pti-2, were found to cause feathered legs in domestic chicken. Breeds with more sparsely feathered legs were supposed to be homozygous mutant (two copies) at the Pti-1 locus but wild-type (pti-2/pti-2) at the second locus. Breeds with more heavily feathered legs like Sultan and Cochin were thought to carry the dominant mutations at both Pti-1 and Pti-2.

In addition, other studies had demonstrated that regulatory mutations in the genes Tbx5 and Pitx1 contribute to foot feathering in domesticated breeds of pigeon.

Andersson and his colleagues wanted to find out which genes and specific mutations correspond to the previously described Pti-1 and Pti-2 loci contributing to foot feathering in chickens---and if these are the same genes as previously identified in pigeon.

In evolution, parallel evolution is known as the independent development of similar phenotypic traits in separate but related lineages. In other words, when faced to adapt, nature can go to the same genetic toolbox to come up with new solutions.

Now, in the advanced online edition of the journal Molecular Biology and Evolution, Andersson and co-authors report that indeed, regulatory mutations in the same genes are responsible for foot feathering in domesticated chickens.

To perform the study and identify the casual mutation of the feathered leg trait in chickens, a three-generation mapping population was established by crossing Langshan (feathered leg) and Houdan (clean leg) chickens, followed by SNP analyses of pooled samples, linkage mapping, whole genome sequencing (WGS), and diagnostic testing of a comprehensive collection of 167 chicken populations with or without feathered legs.

The first predicted causal mutation is a single base change located 25 kb upstream of the gene for the forelimb-specific transcription factor TBX5 on chromosome 15. The
second is a 17.7 kb deletion located about 200 kb upstream of the gene for the hindlimb-specific transcription factor PITX1 on chromosome 13. These mutations are predicted to activate TBX5 and repress PITX1 expression, respectively. Furthermore, the PITX1 causal variants are large overlapping deletions, 17.7 kb in chicken and 44 kb in pigeons.

"The identification of causal mutations in non-coding parts of vertebrate genomes is challenging, due to the difficulty in deducing or experimentally proving functional significance," said Andersson. "Here we have presented strong genetic evidence for causality for two non-coding mutations affecting the feathered leg phenotype in domestic chicken using a very large data-set from chicken with or without feathered legs."

Thus, not only are the same genes involved in foot feathering phenotypes in pigeons and chickens, but the nature of the mutations also very much the same, at least in the case of Pitx1.

The study reveals a remarkable convergence in the evolution of the feathered leg phenotype in domestic chickens and domestic pigeons as this phenotype is caused by non-coding mutations upstream of the same two genes.

"These two cases add to a growing list of regulatory mutations controlling phenotypic traits in domestic animals by altering the expression of important transcription factors," said Andersson. "In fact, the genetic basis of leg feathering is a parallel example to the genetic basis for variation in comb morphology in chickens. Three comb phenotypes Pea-comb, Rose-comb and Duplex-comb, are all structural variants leading to ectopic expression of respectively the SOX5, MNR2, and EOMES transcription factors during comb development."

The manuscript provides strong evidences that foot feathering in chickens has a genetic determinism highly similar to the very same trait in pigeon and confirms that ptilopody has evolved through by running on separate but parallel tracks in chicken and pigeon.

"There is a remarkable convergence as regards the evolution of the feathered leg phenotype in domestic chicken and in domestic pigeons, said Andersson. "The present study illustrates that novel phenotypic traits in domestic animals are often caused by the same mutations across divergent populations because favored mutations have been spread from population to population due to strong phenotypic selection The extensive collection of whole genome sequence data, which is publicly available, provides a powerful resource to identify genomic regions and corresponding causal mutations associated with these phenotypes as successfully accomplished in this study."

"Furthermore, feathered legs occur in many other bird species, for instance in most owls but not in all. If you would like to study the genetic basis for variation in leg feathering within a species or between closely related species, Tbx5 and Pitx1 are the obvious candidate genes to start with," said Leif Andersson.

Philadelphia, April 28, 2020--The cardioprotective drug dexrazoxane preserved cardiac function in pediatric patients undergoing chemotherapy for acute myeloid leukemia (AML) without compromising overall patient survival and potentially improving it, according to a new study by researchers at Children's Hospital of Philadelphia (CHOP). The results suggest dexrazoxane should be considered for cardioprotection in all pediatric patients undergoing standard chemotherapy for AML.

The findings were published today in the Journal of Clinical Oncology.

"This study provides important evidence that using dexrazoxane helps prevent heart damage in children undergoing treatment for AML," said Richard Aplenc, Professor of Pediatrics in the Department of Pediatrics, core faculty member of the Center for Pediatric Clinical Effectiveness at CHOP, and senior author of the study. "These results have arguably changed the standard of care for pediatric AML treatment."

Anthracyclines, a class of drugs used in chemotherapy for cancers such as AML, improve survival in pediatric patients with AML, but the drugs also have cardiac side effects. The drugs generate iron-mediated free radicals and inhibit DNA replication, both of which trigger cell death and left ventricular systolic dysfunction (LVSD) and can lead to heart failure. At least 12% of AML patients experience LVSD within one year of beginning treatment and many also have lower overall rates of survival and increased mortality as a result.

Dexrazoxane is a cardioprotective drug that interferes with iron-mediated free radical formation and cell death caused by anthracyclines. Yet despite consistent evidence of dexrazoxane's cardioprotective benefits, it is used in less than 5% of pediatric AML patients in the United States.

To assess the effectiveness of dexrazoxane in pediatric AML treatment, the researchers collected information on dexrazoxane administration in the most recent clinical trial for AML by the Children's Oncology Group. Whether or not dexrazoxane was used was up to the individual treating physician. Of the 1,092 pediatric AML patients in the trial, 918 were never exposed to dexrazoxane (84%), 96 (9%) received dexrazoxane at each anthracycline administration, and 78 (7%) received dexrazoxane at some but not all of their treatments. Given the scope of their study, the researchers focused only on those patients who received dexrazoxane consistently or not at all.

Patients who received dexrazoxane had significantly lower risk for LVSD than patients who did not (26.5% vs. 42.2%). Patients in both groups had similar 5-year event free survival and overall survival rates, and the results suggest a lower treatment-related mortality among patients who received dexrazoxane (5.7% vs. 12.7%).

Based on these results, the upcoming COG Phase III AML trial will require dexrazoxane use for all patients receiving standard chemotherapy.

"To our knowledge, these data are the first demonstration of a potential survival benefit with dexrazoxane, specifically a reduction in treatment-related mortality," said Kelly D. Getz, PhD, MPH, Assistant Professor of Epidemiology in the University of Pennsylvania Perelman School of Medicine's Department of Biostatistics, Epidemiology, and Informatics and first author of the study. "This suggests that dexrazoxane may directly prevent acute, severe cardiac events that contribute to early deaths. Additional research to understand the underlying biology of anthracycline-associated cardiotoxicity and effective interventions will improve both the cardiovascular and oncologic outcomes for children with cancer."

In one of the first reported cases of its kind, a 3-week-old infant in critical condition recovered from COVID-19 due to rapid recognition and treatment by physicians from McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). The case was published April 22 in the New England Journal of Medicine.

As more data is released on COVID-19, the original belief that pediatric patients are spared from the worst of the disease has been disproven.

"We are still so early in the research and data available on COVID-19, and as providers, we need to be aware that children can get critically ill from this virus," said Alvaro Coronado Munoz, MD, first author and assistant professor of pediatric critical care medicine at McGovern Medical School at UTHealth. "It's important for parents to understand that they should not delay seeking care for their children if there's any presence of fever or trouble breathing."

The child first presented at a local hospital with nasal congestion, rapid breathing, and reduced eating. Physicians there recorded a temperature of 97.0 degrees, high pulse rate, and low oxygen saturation. The child was transferred to a pediatric intensive care unit, and Coronado and other team members were alerted. Upon arrival, the child had low blood pressure and hypothermia, as well as continued rapid heart rate and breathing. Lung X-rays revealed opacity and collapse in one of the upper lobes, indications of pneumonia.

As it was early in the pandemic, it would take a week for test results from a nasal swab to return as positive for the coronavirus, but physicians did not wait before moving into a COVID-19 action plan for the pediatric intensive care unit (PICU).

"Our team was called to admit the patient in PICU, and when we saw the X-ray, we were suspicious immediately that it could be the coronavirus. We took early precautions to protect our team and avoid the spread to health care providers," Coronado said. "We thought the child was sicker than the normal child we see. On top of what appeared to be COVID-19, the child also tested positive for the virus that causes the common cold."

The infant was transferred to a negative-pressure room in the PICU, and was intubated and placed on a mechanical ventilator for five days. While standard PICU protocol calls for noninvasive mechanical ventilation, doctors chose to intubate because the patient was in severe respiratory failure and COVID-19 was suspected. Physicians also placed the infant on a five-day course of hydroxychloroquine and azithromycin.

"Pediatric ICU has to adapt protocols to prevent spread of the coronavirus, such as avoiding aerosolized treatments and considering safe intubation measures sooner than the usual," Coronado said.

After five days, the patient was discharged from the PICU. On day nine, the infant had recovered and was sent home without supplemental oxygen.

"While this case is limited to one single patient, it illustrates that severe COVID-19 cases in children can occur, but also be successfully managed," Coronado said.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summaries below are not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Health Insurance Status and Risk Factors for Poor Outcomes With COVID-19 Among U.S. Health Care Workers: A Cross-Sectional Study

In this brief research report published in Annals of Internal Medicine, researchers from the City University of New York at Hunter College use survey data to assess the number of U.S. health care workers providing direct patient care who have risk factors for a poor outcome if they develop COVID-19 or who lack health insurance or sick leave. Read the full text: http://annals.org/aim/article/doi/10.7326/M20-1874.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author David U. Himmelstein, MD, can be reached through Claure Fauke at clare@pnhp.org.

2. This Time Must Be Different: Disparities During the COVID-19 Pandemic

African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. An editorialist from the University of California, San Francisco discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities. Read the full text: http://annals.org/aim/article/doi/10.7326/M20-2247.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author Kirsten Bibbins-Domingo, PhD, MD, MAS, can be reached directly at Kirsten.Bibbins-Domingo@ucsf.edu.

LA JOLLA--(April 28, 2020) Fruit flies, like many animals, engage in a variety of courtship and fighting behaviors. Now, Salk scientists have uncovered the molecular mechanisms by which two sex-determining genes affect fruit fly behavior. The male flies' courtship and aggression behaviors, they showed, are mediated by two distinct genetic programs. The findings, both published in eLife on April 21, 2020, demonstrate the complexity of the link between sex and behavior.

"Courtship and aggression seem to be controlled somewhat separately by these two genes," says Kenta Asahina, an assistant professor in Salk's Molecular Neurobiology Laboratory and senior author of the two papers. "Having behaviors controlled by different genetic mechanisms can have some benefits in terms of evolution." In other words, he explains, a fly population that is under evolutionary pressure to compete more--perhaps due to limited resources--can evolve aggressive behaviors without affecting courtship.

Male fruit flies' aggression is primarily toward other males, while their courtship behaviors--which involve a series of movements and songs--are toward female flies. Both behaviors are reinforced by evolution over time, because the ability of male flies to compete with other males and attract females directly affects their ability to mate and pass on their genes.

Researchers already knew which neurons in the brain are important for controlling aggression and courtship. In general, studies had suggested that specialized brain cells called P1/pC1 neurons, promote both courtship and aggression while Tk-GAL4FruM neurons promote aggression specifically. They also knew that the two sex-determining genes fruitless (fru) and doublesex (dsx) played key roles in this behavior. But the connection between the genes and the behaviors hadn't been clear.

In the new study, Asahina and his colleagues raised Drosophila fruit flies that contained light-activatable versions of the courtship and aggression neurons. The team could turn the neurons on at any time by shining a light on the flies. The researchers next altered the fru or dsx genes in some of these male flies. They then developed an automated system using machine-learning to analyze videos of the flies and count how often they carried out aggressive or courtship behaviors.

"We made a computer system to capture aggressive behaviors and courtship behaviors to more quickly and accurately count actions," says Salk postdoctoral fellow Kenichi Ishii, co-first author of both of the new papers. "Getting the program to work was actually difficult and time-consuming but in the end, it made it easier for us to get good data."

The team found that dsx was required for the formation of courtship-inducing neurons: when the fruit flies had the female version of dsx, the courtship neurons were no longer present. On the other hand, fru played a different role--without this gene, flies could still be coaxed to perform courtship behaviors by activating courtship neurons but the courtship was directed at both males and females, suggesting that fru was required for flies to differentiate between the sexes. For aggression, however, the findings were the opposite: fru but not dsx was required for the activation of aggression neurons to cause fighting in male flies.

"This is an important example of the neurobiological differences between sexes and what kind of approaches we can use to study sexually-linked behaviors," says Asahina, who holds the Helen McLoraine Developmental Chair in Neurobiology.

"I think the interesting part of this is understanding that sex is really not a binary thing," says UC San Diego doctoral student Margot Wohl, co-first author of both of the new papers. "A lot of factors come together to control behaviors that differ between the sexes."

Since sex determination in flies is very different than in humans--fruit flies don't have sex hormones, for instance--the new findings don't carry over to how biological sex may impact behavior in people. But Asahina says his approach--the combination of optogenetics and sex-linked gene manipulation--may be useful in understanding behaviors that vary by sex in other animals.

Livestock diseases like bluetongue virus (BTV) can have devastating economic and health consequences, but their origins can be difficult to establish. New research published in the open access journal PLOS Biology this week shows that the recent re-emergence of BTV in France could have been caused by human activities, based on the virus' unusual genetic makeup.

Bluetongue virus, a pathogen that infects sheep and cattle, has caused billions of euros of damage to the European farming industry over the last two decades. In the new study, led by researchers at the University of Glasgow (UK) with a consortium of European collaborators, the authors compared genomes of the virus before and after it re-emerged in France in 2015. BTV first arrived in Europe in 2006 from unknown sources. It was controlled through mass vaccination by 2010, and no cases were reported until it re-emerged in 2015. The authors' genome analyses revealed that during both the 2006 and 2015 outbreaks, BTV accumulated novel mutations in a manner expected for a rapidly evolving virus. During the period in between the two outbreaks, however, the researchers noted a curious lack of mutations, indicating that the virus was likely not circulating during this period. The genetic similarity between the original and re-emergent viruses suggests that the 2015 outbreak was caused by infectious material that somehow arose from the first outbreak.

Virus persistence over multiple years in the absence of genetic changes would upset our understanding of virus biology. A more plausible scenario, the authors argue, is that the virus resurfaced after being stored in frozen samples. And since artificial insemination and embryo transfer are widely used in the livestock industry, they say, this transmission mechanism should be evaluated by future work.

Prof. Massimo Palmarini, one of the senior authors of the study says: "In order to survive, to be transmitted and to find new hosts, viruses need to replicate. New mutations are an inevitable consequence of this, so viruses can't remain 'frozen in time'. While there is still lots for us to learn about virus biology, the most plausible explanation for our findings is that exposure to infectious material, stored from the earlier outbreak, caused the most recent emergence of this virus in Europe."