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CHARLOTTE, N.C. - Feb. 3, 2021 - New research on gender inequality indicates that fewer leadership prospects in the workplace apply even to women who show the most promise early on in their academic careers.

Jill Yavorsky, an assistant professor of sociology at UNC Charlotte, co-led the study, "The Under-Utilization of Women's Talent: Academic Achievement and Future Leadership Positions," with Yue Qian, an assistant professor of sociology at the University of British Columbia.

In their paper, published in a leading social science journal, Social Forces, the social scientists discovered that men supervise more individuals in the workplace than women, regardless of their grade point averages (GPAs) in high school. This leadership gap observed during individuals' early to mid-careers was particularly pronounced for those who became parents.

For those who earned a 4.0 GPA in high school, fathers manage more than four times the number of supervisees as mothers (19 for men versus four for women).

Additionally, having a higher GPA is strongly associated with managing more people later in their careers, but this is largely true only for fathers. As high school GPA increases from 0.0 to 4.0, the average number of supervisees increases from 4 to 19 for fathers but barely changes for mothers (increasing from 3 to 4).

Perhaps even more striking is that fathers with very low academic achievement (1.0 GPAs), on average, have similar leadership prospects to women who completed high school with 4.0 GPAs.

"Our research clearly illustrates the barriers that exist for women, especially mothers, in the workplace," said Yavorsky. "At the same time, given that even men with low grades go on to attain higher leadership roles than women, this study highlights perhaps the lack of barriers that men face in securing greater leadership opportunities."

The researchers also examined why this large disparity emerged between mothers and fathers. They discovered that part of the leadership gap by GPA is due to the fact that high-achieving fathers benefit significantly from having a college or advanced degree, whereas comparable mothers do not. Indeed, the leadership opportunities of mothers who have a college degree or higher are similar to those of mothers who do not have a college degree.

The authors explain in their article that men may benefit more from having a college degree than women because men select into or are steered into majors that may offer more leadership opportunities, like those in finance or STEM.

Yavorsky also notes, "Based on other research, we know that even when men and women are in the same field, including female-dominated jobs, men still tend to have higher leadership prospects than women. This suggests that the disparity isn't just due to men and women selecting different career paths. Rather, men benefit in terms of their leadership opportunities regardless of the path they choose."

Additionally, the study found that among top achievers, men had higher leadership prospects than women because they tended to work longer hours in their jobs and had accumulated more work experience than women, particularly after they became parents.

Yavorsky explained that mothers are more likely to have a disproportionate share of household duties than men, take parental leave and disrupt their careers to care for children or others in their family. As a result, men are often able to devote more time to their employers and attain critical job experience that may improve their chances for managerial promotions.

Importantly, even after these explanations, leadership disparities remain between high-achieving mothers and fathers, suggesting that bias and discrimination are also likely at play.

This study focused on a sample of about 5,000 people born between 1957 and 1964. The researchers had access to these individuals' high school transcript data and their responses to how many people they managed over a decade, from 1988 to 1998. According to Yavorsky, the survey used is the most current survey that includes GPA transcript data, tracks adolescents through their early- to mid-careers and captures the number of people they manage in their jobs.

"It is likely that these general patterns hold for younger cohorts, as recent research indicates that progress on many key measures for workplace gender equality has stalled or slowed since the mid-1990s," explained Yavorsky. "Additionally, contemporary research in the field indicates that the COVID-19 pandemic is more negatively affecting women's employment and productivity than men's, in large part because mothers are absorbing more of the responsibilities associated with school and child care closures. This pattern could further exacerbate gender disparities in job experience and therefore future advancement opportunities in the workplace."

Yavorsky noted two key governmental policy changes that could result in greater utilization of women's talent: 1.) subsidized child care to make it more affordable and reliable for all families, and; 2.) paid maternity and paternity leave that encourages fathers to contribute more equitably to household responsibilities from the start of parenthood. She also stated that organizations need to review and better standardize promotion practices to eliminate bias and discrimination, and they should create more pathways to management from female-dominated jobs.

BIRMINGHAM, Ala. - Hypoxia -- where a tissue is deprived of an adequate supply of oxygen -- is a feature inside solid cancer tumors that renders them highly invasive and resistant to treatment. Study of how cells adapt to this critical stressor, by altering their metabolism to survive in a low-oxygen environment, is important to better understand tumor growth and spread.

Researchers led by Rajeev Samant, Ph.D., professor of pathology at the University of Alabama at Birmingham, now report that chronic hypoxia, surprisingly, upregulates RNA polymerase I activity and alters the methylation patterns on ribosomal RNAs. These altered epigenetic marks on the ribosomal RNAs appear to create a pool of specialized ribosomes that can differentially regulate translation of messenger RNA.

This supports a postulate, long debated in biology, that the ribosomal protein factories can be reprogrammed in response to stresses to favor the manufacture of certain proteins.

Ribosomes are macromolecular machines made of ribosomal RNAs and ribosomal proteins, and mammalian cells may have as many as 10 million of them. They sequentially read a messenger RNA that directs the ribosome to add specific amino acids, from of a choice of 20 different amino acids, to a growing peptide chain that folds to form the completed protein. A messenger RNA is a copy of the DNA gene for that protein, and it carries the gene's information for building a protein from the chromosome to the ribosomes.

The finding of significantly increased RNA polymerase I activity in hypoxic breast tumor, mammary epithelial and breast epithelial cell lines that were used as models in the UAB study was unanticipated because RNA polymerase I is the only RNA polymerase used to make ribosomal RNA, and it is strictly regulated. One might expect that hypoxic cells would want to decrease their ribosomal RNA synthesis to save energy, not make more. But in accord with the increased RNA polymerase I that the UAB researchers found in hypoxic cells, there was also increased ribosome biogenesis in both the hypoxic model cell lines and the hypoxic regions of spontaneous tumors in mice, as measured by increased nucleoli and another test.

But were these new ribosomes different from ribosomes found in cells grown under normal oxygen levels?

One major challenge to defining specialized ribosomes has been the lack of a method to selectively isolate a subpopulation of ribosomes that may have functional diversity. To selectively isolate the subpopulation, the UAB team used messenger RNA for a protein called VEGF-C, a protein known to boost the new blood vessel formation called angiogenesis. Hypoxia is known to trigger a switch to angiogenesis and elevated expression of VEGF-C. Furthermore, during hypoxia, VEGF-C messenger RNA is translated by an alternate ribosomal entry point, controlled by the internal ribosome entry site, or IRES, sequence on the VEGF-C messenger RNA.

Samant and colleagues found that hypoxia induced VEGF-C production in their cell models. They were able to use the VEGF-C IRES to pull down hypoxic ribosomes, and they found that these ribosomes had a pattern of methylation on their 18S, 28S and 5.8S ribosomal RNAs that was distinct from the ribosomal RNAs of cells grown in normal oxygen.

In additional detailed work, the UAB researchers sought to unravel clues underlying mechanisms that control changes in ribosomal RNA methylation patterns under hypoxia.

Samant and colleagues found that expression of a protein called NMI was remarkably compromised at the protein and messenger RNA levels during hypoxia. NMI contains a previously uncharacterized RNA recognition motif that can bind single-stranded RNAs.

One class of the single-stranded non-coding RNAs in the cell's nucleolus, called SNORDs, are known to guide the methyltransferase enzyme fibrillarin to methylate specific bases of ribosomal RNA. When the UAB researchers investigated which RNA species could bind to NMI, "to our excitement," Samant said, "we found that many of the top-ranking RNA entities bound to NMI were SNORDs." There are more than 106 SNORDs in human cells to guide methyltransferase to specific sites; NMI bound nine SNORDs that were associated with changes at 14 methylation sites on the hypoxic ribosomal RNAs. NMI also bound the methyltransferase fibrillarin.

"We speculate that NMI acts to regulate the available pool of fibrillarin and SNORDs that can interact, which most likely will affect rRNA methylation patterns," Samant said.

One of the most important ways to stop the spread of COVID-19 is for people who have tested positive, or have symptoms, to isolate themselves from the other people they live with.

But a new University of Michigan poll suggests that nearly one in five older adults don't have the ability to do this - and that those who are Hispanic or Black, or who have lower incomes or poor health to begin with, are more likely to lack a safe isolation place in their home.

The poll also shows significant inequality in another key aspect of staying safe and healthy during the pandemic: the ability to get outside for fresh air and exercise, and to engage safely with friends, neighbors and relatives in open air.

Older adults who had more access to outdoor spaces around their home, and those who could walk to greenspaces like parks, gardens or woods, were more likely to engage in the kinds of outdoor activities and safe social connections that experts urge everyone to engage in during the pandemic. But that access also varied by income, race/ethnicity and health status.

The poll shows how important the 'built environment' of housing and local outdoor public spaces is to the health of older adults, says the team that conducted the poll as part of the National Poll on Healthy Aging, based at U-M's Institute for Healthcare Policy and Innovation.

The poll receives support from AARP and Michigan Medicine, U-M's academic medical center, and draws from the answers of a national sample of more than 2,000 adults aged 50 to 80.

"These findings build on what we already know about the link between a person's home and community environment, and their engagement in health-promoting activities, but through the lens of a pandemic that disproportionately affects older adults, adults of color and low-income people," says Upali Nanda, Ph.D., an associate professor in U-M's Taubman College of Architecture & Urban Planning.

"In the short term, recommendations by health officials and health care providers should take these disparities into account," says Andrew Ibrahim, M.D., M.Sc., a surgeon and health care researcher at Michigan Medicine. "In the long term, architects and urban planners should see the lessons from this report as evidence that they can and should be front-line workers for the health of communities."

More about the poll findings

The ability to isolate from others in the same living space when sick with COVID-19, or known to be infected with the novel coronavirus, is critical to preventing others from getting sick. This is especially important for people who live with others who are at higher risk if they develop COVID-19, such as people over 50, people with underlying conditions such as obesity, diabetes and lung disease, and people who have weakened immune systems.

The Centers for Disease Control and Prevention recommends that people with the disease or a positive COVID-19 test result should isolate in a separate room, and use a separate bathroom if possible. The people who live with them should take other precautions to protect themselves.

"Research has proven that COVID-19 can spread easily within homes, so that's why it's concerning that 18% of people over 50 don't have a way to do so, and that this rose to 27% among those who say they're in fair or poor health, which may indicate a higher risk of severe COVID-19," says Preeti Malani, M.D., the poll director and a Michigan Medicine physician specializing in geriatrics and infectious diseases. "The disparities we saw in the poll suggest differences in living arrangements may be playing a larger role in the pandemic than we thought, and point to a need for health providers and public health officials to advise the public on ways to stay safe depending on their individual living situation."

For instance, if there's only one bedroom, the infected person should isolate there, and uninfected people should sleep on a couch or mattress in the living room. Uninfected people who live with someone with a known case of COVID-19 should also quarantine, which means staying home and not going to stores, work, school or on outings - but missing work can be hard or impossible for low-income people who work independently or in frontline hourly jobs.

Nearly a third of Hispanic poll respondents (31%) said they didn't have a place to isolate in their home, compared with 25% of Black respondents and 14% of white respondents. People with household incomes under $30,000 were more than twice as likely as those with incomes over $100,000 to say they lack a safe isolation space. Apartment dwellers were more than twice as likely as those who live in single-family detached homes to say they had no place to isolate.

On the flip side of the pandemic, living arrangements can affect older adults' ability to stay positive, healthy and socially engaged during the pandemic, the poll finds. While most of the older adults said they had an outdoor space where they could safely connect with neighbors, 32% don't live within walking distance of a greenspace.

That percentage was higher for Blacks (46%) and Hispanics (50%), and for people with incomes under $30,000 (51%). There were statistically significant differences by race/ethnicity, income, and health status in having a view of nature, place to safely connect with neighbors, and greenspace within walking distance.

"It's important that communities be livable for people of all ages, including access to work, shopping, recreation and public places," says Alison Bryant, Ph.D., senior vice president of research for AARP. "Despite the documented desire of most older adults to stay in their homes and communities as they age, research from AARP has found that most older adults do not reside in highly livable communities, and there is much more that could be done to help old adults age where they currently live."

Three-quarters of respondents said they had spent time outdoors or interacted with nature at least a few times per week in the first months of the pandemic. Nearly half had walked or bicycled around their neighborhood at least a few times a week in that time, too. Those who had access to outdoor spaces and nearby greenspaces were more likely to have done so.

A can of Red Bull next to the computer mouse, a bag of potato chips next to the keyboard - that's how many people imagine nutrition in eSports. "The energy drink is indeed part of the diet for many," says Professor Ingo Froböse, head of the Institute of Movement Therapy and movement-oriented Prevention and Rehabilitation at the German Sport University Cologne, "but overall, eSports players actually eat better than the general population."

This is the result of the third eSport study by the German Sport University Cologne, which was presented in Cologne on February 3, 2021. The two previous eSport studies focused on training and health behavior as well as media consumption and mental well-being; this year's survey concentrates on nutrition. Together with the AOK Rhineland/Hamburg, Univ.-Prof. Dr. Ingo Froböse surveyed about 820 eSport athletes of all skill levels. A special challenge this year: Due to the restrictions caused by the COVID-19 pandemic, the data of the eSport Study 2021 was not collected at eSport events, but completely online.

Energy drinks are part of eSports

The consumption of energy drinks, which is often associated with eSports, is more than just a cliché. Around 40 percent of respondents consume the drinks regularly, drinking just over one can per week on average.
Energy drink manufacturers have been sponsoring major eSports events and teams for years. In addition, many of these drinks are associated with a supposed increase in performance and thus appear particularly attractive for eSports players. These marketing strategies could well explain why consumption among gamers is above average. "The high amounts of sugar in these beverages should of course be viewed negatively from a health science perspective. Accordingly, consumption should be significantly reduced," says Froböse, who recommends a handful of nuts and lightly sweetened tea instead for an energy boost in the game.

Nevertheless, overall sugar consumption is significantly lower than that of the general population. Whether soft drinks, chocolate or other sweets, eSport players consume less than other groups. An average of one bar of chocolate per week and a small bowl of salty snacks indicate health-conscious eating behavior.

Furthermore, fast food and ready-to-eat products are only eaten twice a week on average. The cliché of a quick slice of pizza in front of the console therefore seems to be outdated.

Meat is preferred to vegetables

However, there is still a need for optimization. "We see the same problem among eSport athletes as in the general population: there is still too much meat and too few vegetables on the menu," Froböse concludes. While the German Nutrition Society recommends five portions of fruit and vegetables a day, just 15 percent of the men and 25 percent of the women surveyed achieve this recommendation. Although an above-average proportion of eSport players are vegetarians or vegans (14.8 %), the remaining group eats meat almost every day. "In particular, the consumption of red meat, which is associated with negative effects on health, should be reduced accordingly," explains Froböse.

DIY cooking is the trend

The survey results show that half of all respondents do their own cooking at least five days a week. Only five percent of respondents leave the cooking of meals completely to someone else. This is even more astonishing when one considers that the group of esport players consists of 86 percent men, who, who actually cook rather rarely according to previous studies. "Of course, we hope that this development will continue after the pandemic. Those who cook for themselves also decide what ends up in the cooking pot. This is the first step towards a healthy and balanced diet," explains Rolf Buchwitz, Deputy Chairman of the Board of the AOK Rhineland/Hamburg.

No negative influence from the pandemic

The results of the study also reveal that the pandemic has only a minor impact on the health behavior of the respondents. As in previous years, the average level of physical activity among the target group is well above the recommendations of the World Health Organization. The eSports players spend more than nine and a half hours per week on physical activity. That's about an hour more than that of respondents of last year's study. Almost all respondents also still rate their health and well-being as good. "We would have expected the pandemic and the accompanying restrictions on everyday life to have a negative impact on the respondents' own health ratings and sense of well-being. Instead, the target group was able to maintain the level of previous years and even improve it in some cases," says Froböse.

Still potential for optimization overall

"In general, the clichés of the junk-food-eating gamer are outdated," concludes Froböse on the eSports study 2021. "Reducing the consumption of meat and energy drinks can be an important starting point for targeted health promotion that takes both health and performance of eSport players to the next level."

As the sea ice shrinks in the Arctic, the plankton community that produces food for the entire marine food chain is changing. New research shows that a potentially toxic species of plankton algae that lives both by doing photosynthesis and absorbing food may become an important player in the Arctic Ocean as the future sea ice becomes thinner and thinner.

Microscopic plankton algae, invisible to the naked eye, are the foundation of the marine food web, feeding all the ocean´s living creatures from small crustaceans to large whales. Plankton algae need light and nutrients to produce food by photosynthesis.

A thick layer of sea ice - sometimes covered with snow - can reduce how much sunlight penetrates into the water and stop the algae getting enough light. However, as the sea ice is becoming thinner and less widespread in the Arctic, more and more light is penetrating into the sea. Does this mean more plankton algae and thus more food for more fish, whales and seabirds in the Arctic? The story is not so simple.

More light in the sea will only lead to a higher production of plankton algae if they also have enough nutrients - and this is often not the case. With the recent increase in freshwater melt from Arctic glaciers and the general freshening of the Arctic Ocean, more and more fresh and nutrient-depleted water is running out into the fjords and further out into the sea. The fresher water lies on top of the more salty ocean and stops nutrients from the deeper layers from mixing up towards the surface where there is light. And it is only here that plankton algae can be active.

Mixotrophic algae play on several strings

However, a brand new study published today in the renowned journal Nature - Scientific Reports shows that so-called mixotrophic plankton algae may play a crucial role in the production of food in the Arctic Sea.

Mixotrophic algae are small, single-celled plankton algae that can perform photosynthesis but also obtain energy by eating other algae and bacteria. This allows them to stay alive and grow even when their photosynthesis does not have enough light and nutrients in the water.

In northeast Greenland, a team of researchers measured the production of plankton algae under the sea ice in the high-Arctic fjord Young Sound, located near Daneborg.

"We showed that the plankton algae under the sea ice actually produced up to half of the total annual plankton production in the fjord," says Dorte H. Søgaard from the Greenland Climate Research Centre, Greenland Institute of Natural Resources and the Arctic Research Centre, Aarhus University, who headed the study.

"Mixotrophic plankton algae have the advantage that they can sustain themselves by eating other algae and bacteria as a supplement to photosynthesis when there isn't enough light. This means that they are ready to perform photosynthesis even when very little light penetrates into the sea. In addition, many mixotrophic algae can live in relatively fresh water and at very low concentrations of nutrients - conditions that often prevail in the water layers under the sea ice in the spring when the ice melts," Dorte H. Søgaard explains.

Toxic algae kill fish

For nine days, the researchers measured an algal bloom driven by mixotrophic algae occurring under the thick but melting sea ice in Young Sound during the Arctic spring in July, as the sun gained more power and more melt ponds spread across the sea ice, gradually letting through more light.

The algae belong to a group called haptophytes. Many of these algae are toxic, and in this study they bloomed in quantities similar to those previously observed in the Skagerrak near southern Norway. Here, the toxic plankton algae killed large amounts of salmon in Norwegian fish farms.

"We know that haptophytes often appear in areas with low salinity - as seen in the Baltic Sea, for example. It is therefore very probable that these mixotrophic-driven algae blooms will appear more frequently in a more freshwater-influenced future Arctic Ocean and that this shift in dominant algae to a mixotrophic algae species might have a large ecological and socio-economic impact." says Dorte H. Søgaard.

The researchers behind the project point out that it is the first time that a bloom of mixotrophic algae has been recorded under the sea ice in the Arctic.

Cities have become critical players in reducing the greenhouse gas (GHG) emissions that are causing global climate change. Urban areas produce almost 70 percent of those emissions, and city governments are proposing a variety of policy actions aimed at reducing them. Many cities also produce inventories that detail their greenhouse gas emissions.

Now, professor Kevin Gurney of Northern Arizona University's School of Informatics, Computing, and Cyber Systems and colleagues have compared the self-reported emissions inventories published by 48 major U.S. cities to estimates from a state-of-the-art emissions information system. As described in Nature Communications, Gurney and his research collaborators found large differences and a systematic under-reporting of urban emissions by cities.

Gurney, who specializes in atmospheric science, ecology and climate policy, has spent the past two decades developing a standardized system for quantifying greenhouse gas emissions under his Vulcan and Hestia Projects. The system, funded by National Aeronautics and Space Administration (NASA) and the National Institute of Standards and Technology (NIST), quantifies and visualizes greenhouse gases emitted across the entire country down to individual power plants, neighborhoods and roadways.

The emissions estimates generated by the system help identify problem areas and enable better decisions about where to cut emissions most effectively. Two recent studies, at the nationwide level (link) and within the city of Indianapolis, IN (link), have shown that Gurney's estimates are consistent with estimates based on direct atmospheric monitoring, a key independent form of independent validation.

Climate change policies in cities are rapidly progressing, and cities often rely on their self-reported inventories when developing their policies, Gurney compared 48 of these self-reported inventories from U.S. cities to emissions estimated by his Vulcan information system. The cities in the study included New York, Chicago, Los Angeles, Dallas, Denver and Philadelphia.

"The results of this comparison were surprising," Gurney said. "The differences were large and varied widely from one city to the next. When averaged, the self-reported emissions were almost 20 percent below the emissions estimated by the Vulcan system." But that average doesn't tell the whole story: for example, Cleveland, Ohio reported emissions 90.1 percent below the Vulcan estimate while Palo Alto, Calif., reported emissions 41.7 percent greater than the Vulcan estimate.

In order to prioritize and track emission reductions, cities will need an unbiased understanding of their emissions.
"The adage 'you can't manage what you can't measure' is really applicable here," Gurney said. "Cities need a comprehensive and accurate assessment of their emissions. Without it, they could target the wrong emissions sources in their landscape for emission reduction or think they are on an emissions trajectory to meet their target, when in fact, they are not."

For example, the city of Indianapolis aims to make a 20 percent reduction in GHG emissions from buildings by 2025 relative to 2016 values. With the 26.9 percent underestimate found in the study, it will be difficult to track progress towards this target or know when and if it has been achieved.

"Consistency in estimating emissions from one city to the next is also critical to comparing and contrasting different mitigation approaches and policies," said Gurney. "This allows cities to borrow emission mitigation policies from others with similar emission characteristics. The inconsistencies in self-reported inventories make that very difficult."

The approach taken by the research team uses a consistent method across all cities in the U.S., combining federal, state, and local data systematically.

"It is expensive and time-consuming for cities to build accurate urban greenhouse gas inventories," said Geoffrey Roest, an NAU postdoctoral researcher and co-author of the study. "But we have emissions data for every city in the U.S., and we can collaborate with cities to help them produce comprehensive, accurate inventories from that data."
The research team found that the differences between the self-reported inventories and the Vulcan estimates were likely due to cities' not accounting for particular fuels or sectors where local information was limited or difficult to come by.

"Vulcan data can be adapted to meet the needs of different cities by incorporating local data" said Yang Song, an NAU postdoctoral researcher and co-author on the study. "This will help cities identify the most effective strategies towards true and lasting emission reductions backed by the best science."

Australia's and New Zealand's first set of clinical guidelines for children's head injuries has been created by a network of specialists based at the Murdoch Children's Research Institute (MCRI).

The guidelines, developed by the Paediatric Research in Emergency Departments International Collaborative (PREDICT) and published in Emergency Medicine Australasia, will allow emergency department clinicians to best diagnose and treat children's head injuries while reducing unnecessary exposure to radiation from CT scans. They also address head injuries in children with underlying problems, such as a bleeding disorder.

Matthew Salter took his son Jakob, 15, to the emergency department of a major hospital late last year after he knocked his head after a BMX crash.

"Jakob attempted to do a bike trick at one of our local BMX tracks but he mistimed the landing and crashed headfirst," he said. "When my wife and I arrived onsite, we found the visor on his helmet had been smashed off, he was distressed and I was worried he may have suffered a concussion.

"When we arrived at the hospital he vomited a few times so to rule out a head injury he received a CT scan and was observed overnight."

Under the new head injury guidelines, Jakob fulfilled several risk factors for a CT scan and observation.

Mr Salter said it was comforting to know these guidelines were in place to ensure all children received the same treatment regardless of where they lived in Australia.

Professor Franz Babl, MCRI Group Leader of Emergency Research, said Australia and New Zealand have not had a specific set of guidelines to help clinicians decide how best to treat individual children under 18 years who come to the emergency department with mild to moderate head injury.

"While we need to rule out any bleeding in the brain, we don't want to order CT scans unnecessarily, because it increases children's lifetime radiation exposure," he said.

"The lack of standardised guidelines meant children were receiving different care depending on where they were seen. Widespread uptake of these guidelines will change that."

Following an extensive search and assessment of international guidelines such as those used in Canada, the US and the UK, the PREDICT working group developed 71 recommendations and an imaging/observation algorithm relevant to the Australian and New Zealand setting. The new guidelines cover patient triage, imaging, observation versus admission, transfer, discharge and follow-up.

Head injury is one of the most common reasons for children to present to emergency departments.

In Australia and New Zealand about 10 per cent of children who present with head injuries of all severities have CT scans. Despite traumatic brain injuries being uncommon, persistent post-concussive symptoms affect more than a third.

Professor Stuart Dalziel, Cure Kids Chair of Child Health Research at The University of Auckland and paediatric emergency physician at Starship Children's Hospital in New Zealand, said identifying traumatic brain injury in children with seemingly mild injuries could be difficult and over the past 15 years had been a focus of research in emergency departments worldwide.

He said across Australia and New Zealand there had been a variation in practice in the management of paediatric head injury.

The PREDICT working group who developed the guidelines included emergency physicians, pediatricians, neurologists, neurosurgeons, radiologists, sports medicine doctors, neuropsychologists, GPs, paramedics and nurses.

The guidelines can be viewed at predict.org.au

A decision-support tool that could be accessed via mobile devices may help clinicians in lower-resource settings avoid unnecessary antibiotic prescriptions for children with diarrhoea, a study published today in eLife shows.

The preliminary findings suggest that incorporating real-time environmental, epidemiologic, and clinical data into an easy-to-access, electronic tool could help clinicians appropriately treat children with diarrhoea even when testing is not available. This could help avoid the overuse of antibiotics, which contributes to the emergence of drug-resistant bacteria.

"Diarrhoea is a common condition among children in low-resource settings," explains lead author Benjamin Brintz, Research Associate at the Division of Epidemiology, University of Utah Health, Salt Lake City, US. "Antibiotics are often prescribed for it, despite the fact these medications will not help patients who have diarrhoea caused by viruses. Helping clinicians determine if a case of diarrhoea is likely caused by a virus or bacteria could help reduce inappropriate antibiotic prescriptions."

In their study, Brintz and his colleagues developed a statistical model that integrated multiple sources of real-time data to help clinicians determine whether a child's diarrhoea was caused by bacteria or a virus. This included information about prior patients, the seasons, and weather, which is useful because some viruses are seasonal in nature and certain bacterial infections may be spread by flooding or similar conditions.

To account for interruptions to electronic information sources, which can be frequent in some settings, the team built the model so it would still work if some of the information was missing. They also optimised it for use on mobile devices. They then tested how well the model would work if it were applied to real cases of diarrhoea in paediatric patients. Their results showed that it could reduce inappropriate antibiotic prescriptions by more than 50%.

The authors say the next step in their research will be to ensure the tool provides enough certainty that clinicians can trust it, and that it will not lead to patients who require antibiotics being undertreated. But if this decision aid can meet these high standards, it could be a valuable resource for clinicians with limited diagnostic tools who often rely solely on their best professional judgement.

"The global burden of diarrhoea is highest in low- and middle-income countries, where there is limited access to laboratory testing," concludes senior author Daniel Leung, Associate Professor of Internal Medicine (Infectious Disease), and Adjunct Associate Professor of Pathology (Microbiology and Immunology), at University of Utah Health. "The care of children in these regions could greatly benefit from an accurate and flexible decision-making tool."

FRANKFURT. Chronic liver disease and even cirrhosis can go unnoticed for a long time because many patients have no symptoms: the liver suffers silently. When the body is no longer able to compensate for the liver's declining performance, the condition deteriorates dramatically in a very short time: tissue fluid collects in the abdomen (ascites), internal bleeding occurs in the oesophagus and elsewhere, and the brain is at risk of being poisoned by metabolic products. This acute decompensation of liver cirrhosis can develop into acute-on-chronic liver failure with inflammatory reactions throughout the body and failure of several organs.

In the PREDICT study, led by Professor Jonel Trebicka, scientists from 15 European countries observed 1273 patients who were hospitalized with acute decompensation of their liver cirrhosis. The current evaluation of the study focused on the question of what can trigger acute decompensation of liver cirrhosis. The result: in the vast majority of cases (>90%), a bacterial infection, liver inflammation caused by alcohol consumption, or both together could be identified as the trigger.

Bleeding in the digestive tract and brain dysfunction induced by painkillers or sedatives (drug-induced toxic encephalopathy) were identified as further trigger, although at a lower rate.

Lead investigator Professor Jonel Trebicka, gastroenterologist and hepatologist at the Medical Clinic I of the University Hospital Frankfurt, explains: "The acute decompensation of liver cirrhosis demands rapid and targeted action. In the PREDICT study, we therefore want to learn a lot about the triggering factors of this life-threatening disease in order to be able to derive recommendations for diagnostics and therapy. Knowing what the most likely triggers of acute decompensation are will help to further develop diagnostic and treatment strategies for patients with this life-threatening disease."

JUPITER, FL - A collaboration led by Scripps Research has developed a way to separate the beneficial anti-inflammatory properties of a group of steroids called glucocorticoids from some of their unwanted side-effects, through an optimization process they named "ligand class analysis."

Their process enabled them to engineer two new, drug-like compounds that show steroidal anti-inflammatory action and other specific traits. One boosts muscle and energy supply, while the other reduces risk of muscle-wasting and bone loss typical of such drugs.

Their report, titled, "Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling," appeared Jan. 28 in the journal Nature Chemical Biology.

Glucocorticoids are steroid hormones, a group that includes cortisone, prednisone and dexamethasone. Among the most frequently prescribed of medications, their anti-inflammatory properties make them useful in an array of forms and doses.

Glucocorticoids are used as injections for hip or back pain, tablets for autoimmune disease, nasal spray for sinus congestion, anti-itch cremes for soothing rashes or insect bites, and more.

Most recently, the glucocorticoid drug dexamethasone has become the standard of care for COVID-19 treatment later in illness, as it can help quiet overaggressive immune attacks in delicate lung tissue and blood vessels.

But glucocorticoids are also among the more problematic of medicines, as prolonged use or high doses can lead to adverse events including high blood pressure, muscle wasting, bone loss, vulnerability to infections, vision problems, anxiety, swelling, weight gain, high blood sugar, insulin resistance, diabetes, and more, while naturally occurring glucocorticoids in the body can contribute to prostate cancer progression.

Pursuing safety

A key goal of the team was to engineer more precise glucocorticoids able to act in tissue-specific or activity-specific way, while limiting specific adverse events, says the study's lead author, Kendall Nettles, PhD, associate professor of Integrative and Structural Biology at the Scripps Research, Florida campus.

"There is a great unmet need to improve glucocorticoids," Nettles says. "We asked, 'Can we develop glucocorticoids that have more selective effects on inflammation and the immune system, instead of hitting the body with a hammer?' This method is showing that we can do that now."

The project pooled the expertise of many collaborators, in areas including chemistry, bioinformatics, structural biology, proteomics, genomics, cell metabolism and more. Contributors included Scripps Research, Florida-based faculty and their scientific staff and students; a researcher from the institute's California-based drug discovery division, Calibr, and scientists from Weill Cornell Medicine, Emory University School of Medicine, the National Cancer Institute and others.

Nettles says their "ligand class analysis" process began with selection of a known corticosteroid compound. Scripps Research chemist Theodore Kamenecka, PhD, modified the compound in many ways to build a collection of new molecules.

One substitution at a time, the scientists created 22 new compounds that showed an ability to actively bind with cell receptors for steroids. They then devised an experimental platform for testing precisely how these compounds affected muscle, bone and lung cells, to indicate each one's risk of causing muscle loss or bone loss, while keeping anti-inflammatory activity.

One of the greatest challenges they encountered was devising a way to accurately test the molecules in cultured cells, Nettles says. At first, they seemed to require 1,000 times more compound than expected to measure impact.

Stress produces results

First author Nelson Bruno had the breakthrough idea of testing only after stress, specifically, fasting followed by brief insulin challenge. That's because stress is the trigger for release of endogenous steroid hormones in real life, Nettles explains.

"It took us two years just to develop the experimental assays to reproduce the effects of what glucocorticoids do in people," Nettles says. "We found we needed realistic physiology."

They also used a machine learning approach to predict how the compounds would affect insulin receptor signaling, gene transcription, protein balance and glucose disposal in the cells, depending on chemical structure.

Through repeated challenges and tests in the cells and in mice, they settled on two compounds, SR11466 and SR16024, as ones with medically useful traits including inflammation control, plus muscle-sparing ability, or mitochondria-building potential. Mitochondria convert cellular nutrients into energy.

The process they developed to refine the compounds has implications well beyond the improvement of glucocorticoids, Nettles adds. It can power more-selective drug-discovery for any number of medicines that work via the cell surface and nuclear receptors to impact signaling and gene transcription in cells, he says.

This project started long before the COVID-19 pandemic began, Nettles says, but it has potential to benefit people sickened with COVID-19. In the context of an infectious disease, the ideal anti-inflammatory would be one that suppressed overly aggressive immune attack without impairing ability to fight off infection, so that's the next goal, he says. More work is needed to address bone loss risk as well, he says.

"These drugs could be used more widely if we could reduce the side-effects profile," Nettles says. "We brought together many recent scientific advances to address a significant problem that affects huge numbers of people. Our findings show that using ligand class analysis, we can potentially improve the safety and specificity of steroids and other needed medicines."

TAMPA, Fla. -- Chimeric antigen receptor T-cell therapy, or CAR T, has been a breakthrough in the treatment of blood cancers such as acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Clinical studies have shown overall response rates of more than 80% with an ongoing response of nearly 40% more than two years after therapy. However, the cellular immunotherapy doesn't work for every patient. Moffitt Cancer Center, one of the leading centers for cellular immunotherapy, is researching why some patients have a better CAR T response than others and what can be done to improve the treatment's effectiveness. In a new study published in Blood, the official journal of the American Society of Hematology, Moffitt researchers show that immune dysregulation can directly affect the efficacy of CAR T therapy in patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. It is an aggressive cancer affecting B lymphocytes, a type of white blood cell that helps the body fight infection. Axicabtagene ciloleucel was the first CAR T therapy approved for the treatment of this type of cancer. It is indicated for patients with refractory or relapsed disease, meaning they have failed two or more prior courses of therapy. For CAR T-cell therapy, a patient's immune cells are collected through a process called apheresis. Those immune cells are genetically modified in a lab, adding a chimeric antigen receptor that helps the T cells locate and kill tumor cells once infused back into the patient.

For this observational study, the research team collected blood and tumor samples from 105 patients treated with axicabtagene ciloleucel. The samples, which were taken before and after therapy, were analyzed. Patients were categorized into two groups: durable responders, meaning they remained in remission at a minimum follow-up of six months following CAR T infusion, and nondurable responders who experienced relapsed lymphoma.

"Large B cell lymphoma patients with active disease already experience immune dysregulation, such as elevated cytokines, altered myeloid cell populations and T cell deficits. Our analysis was to determine how these immune characteristics and inflammation affect the ability for CAR T cells to expand and seek out cancer cells following infusion," said Frederick Locke, M.D., vice chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department and co-leader of the Immuno-Oncology Program at Moffitt.

The results showed that large tumors lead to immune dysregulation in patients due to chronic interferon signaling within the tumor and high cytokine levels in the patient. Overall, CAR T-cell therapy was less likely to be successful in patients with immune dysregulation. This was attributed to impairment of the growth of CAR T cells in these patients, as well as resistance to CAR T-cell therapy by the tumor due to the expression of multiple immune checkpoints.

"These findings could help improve the way we administer CAR T therapy on two fronts. We can use interventions to help improve the quality of patients' immune cells prior to apheresis, resulting in a better CAR T product. We can also help better prepare patients' immune systems to receive the CAR T cells to increase response following infusion," said Michael Jain, M.D., Ph.D., assistant member of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt.

The researchers stress more study is needed to determine what those interventions would be, but there is hope these findings can help modify therapy to reduce relapses that occur following CAR T therapy.

New research has found that men who have the Western world's most common genetic disorder are more likely to develop dementia, compared to those without the faulty genes.

Researchers at the University of Exeter and the University of Connecticut have previously found that men with two faulty genes that cause the iron overload condition haemochromatosis are more likely to develop liver cancer, arthritis and frailty, compared to those without the faulty genes.

Now, the team's new analysis of more than 335,000 people of European ancestry in UK Biobank, funded by the Medical Research Council and published in the Journal of Alzheimer's Disease, has found that men who carry the two faulty genes that cause haemochromatosis are more likely to develop dementia than men who do not carry any copies of the faulty gene.

The latest study analysed 2,890 men and women, aged 40-70 years with two faulty haemochromatosis genes (called HFE C282Y homozygous) in UK Biobank. The team found that 25 of the 1,294 men with the two faulty genes went on to develop dementia, which was 83 per cent more common than for those without the faulty genes. The team also found a build-up of iron in key areas of the brain linked to dementia, in a subset of men with two faulty genes that cause hemochromatosis. The same group of men were also significantly more likely to develop delirium, itself linked to dementia, over a ten-year follow-up. These findings could influence calls for the UK National Screening Committee to recommend screening for the condition, which is currently under consultation.

Haemochromatosis causes a build-up of iron around the body. An estimated 175,000 men and boys of European ancestry in the UK have the two faulty genes that cause haemochromatosis. The disorder is known as the "Celtic curse" because it is particularly prevalent in Celtic bloodlines.
Reliable tests are available to identify those at risk - blood tests for measuring iron levels and genetic testing. Symptoms can include feeling tired all the time, muscle weakness and joint pains, meaning it is often misdiagnosed as the signs of ageing. Once diagnosed, the condition is easily treated by a process similar to donating blood several times a year, to lower iron levels.

Lead author Dr Janice Atkins, of the University of Exeter Medical School said: "We know that a build-up of iron in the brain is linked to dementia in people without haemochromatosis. Our study is the first to show that men with the mutations for haemochromatosis may have a substantially increased risk of dementia, although the numbers of people who develop dementia are still low. We now need more research to establish whether the genetic condition causes brain decline, particularly as haemochromatosis is easy to treat, and could be a route to preventing some dementia."

Professor David Melzer, who leads the research group in Exeter said: "In the past, there was debate about whether having the haemochromatosis faulty genes caused excess disease. It is now clear that these genes cause high rates of liver cancer and increased rates of several diseases including dementia. We now urgently need clinical trials of early diagnosis and treatment for people with the haemochromatosis genes in the UK, to pave the way to a screening program for this condition."

Of those 1,294 men with two faulty genes, 78 participated in an MRI study which included brain scanning. Their data were compared to 11,082 participants who did not have the two faulty genes. The brain imaging data on men with the two faulty genes for haemochromatosis found a build-up of iron in areas of the brain including the hippocampus and thalamus, known to be linked to memory.

Haemochromatosis tends to be more serious in men, with women partially protected because they lose iron through menstruation and childbirth, although some younger women do develop the disease. The study found no increase in dementia risk in women with faulty haemochromatosis genes.

Dr David Steffens, Professor and Chair of the Department of Psychiatry at the University of Connecticut School of Medicine and a co-author of the paper, noted: "This study adds to the list of modifiable factors that may point to prevention of dementia. If our results are replicated, it may become routine for clinicians to test for hemochromatosis in the evaluation of patients with memory complaints and in the screening of older asymptomatic patients."

Neil McClements, Chief Executive of the charity Haemochromatosis UK, said: "This study furthers our understanding of the toxic effects of excess iron on the body. It's important that families with genetic haemochromatosis get their relatives screened for the condition. Early diagnosis saves lives and improves quality of life, too."

The NHS advises that it is important to talk to your GP if you have a parent or sibling with haemochromatosis, even if you don't have symptoms yourself - tests can be done to check if you're at risk of developing problems. People are also advised to talk to their GPs about haemochromatosis if they have the following persistent or worrying symptoms - particularly if you have a northern European family background. Typical symptoms include feeling very tired all the time (fatigue); weight loss; weakness and joint pain. Also, some men with haemochromatosis develop an inability to get or maintain an erection (erectile dysfunction), and some women have irregular periods or absent periods. These symptoms usually come on between ages 30 and 60.

Recent global calamities - the pandemic, wildfires, floods - are spurring interdisciplinary scientists to nudge aside the fashionable First Law of Geography that dictates "everything is related to everything else, but near things are more related than distant things."

Geography, and by association, ecology, has largely followed what's known as Tobler's Law, which took hold in the early 1970s. But then came the novel coronavirus apparently has leapt from wildlife meat markets in China to the world in a matter of months. Global climate change creates conditions ripe for infernos in the North American west and Australia. Extreme Ohio flooding in 2018 gave way to sediments and excessive nutrients to dump into the Gulf of Mexico to the tune of some 300 square kilometers.

In other words, all that's local is a lot more global, and the scientists in this week's Frontiers in Ecology and the Environment say solutions can only be found through broader views and collaborations nearby and far away.

"Understanding and finding solutions to the recent and future crises need an integrated framework across local to global scales," said Jianguo "Jack" Liu, Michigan State University's (MSU) Rachel Carson Chair in Sustainability.

Liu has introduced the framework of metacoupling, which allows scientists to view the world as it truly is - with humans and nature interacting over space and time and without boundaries of academic disciplines. The metacoupling framework lets scientists understand how actions locally, nearby and far away - like policies that regulate the sale of wild animals or affect the release of greenhouse gasses - result more in just cause and effect. Actions bounce back and forth between humans and nature from the community nearby and the country on the other side of the world. These are examples of feedback, and there are impacts that spill over in between. The paper notes that the metacoupling inserts the human element into the equation - both where events happen, and where our impact is felt, and the spaces in between.

In other words, for much of environmental sciences, Tobler's Law and its geography focus is going the way of tube tops and tie-dye in favor of what the authors say is "a more comprehensive understanding of human-natural systems will emerge through this approach as a requisite for addressing today's large-scale ecological problems, and this will be part of the "evolution" of the new field of macrosystems biology."

Lead author Flavia Tromboni says the paper delivers a message that science indeed must evolve to capture the world as it is - and where it is going. "We cannot capture the magnitude of human impacts globally and be able to find solutions for pressing global environmental issues without considering all these multi-scale interactions," she said. Tromboni is a research assistant professor in the Global Water Center of the University of Nevada, Reno.

Other authors of "Macrosystems as metacoupled human and natural systems" note the issues keep unfolding. Kyla Dahlin, an assistant professor in MSU's Department of Geography, Environment, and Spatial Sciences, points out today's western wildfires already are leading to questions about crops - and ultimately grocery store prices -hundreds of miles away. "Metacoupling especially breaks with the idea of Tobler's Law," she said.

CORVALLIS, Ore. - Extensive sea ice covered the world's oceans during the last ice age, which prevented oxygen from penetrating into the deep ocean waters, complicating the relationship between oxygen and carbon, a new study has found.

"The sea ice is effectively like a closed window for the ocean," said Andreas Schmittner, a climate scientist at Oregon State University and co-author on the paper. "The closed window keeps fresh air out; the sea ice acted as a barrier to keep oxygen from entering the ocean, like stale air in a room full of people. If you open the window, oxygen from outside can come in and the air is not as stale."

The findings, published recently in Nature Geoscience, challenge previous assumptions about the relationship between oxygen and carbon dioxide in deep ocean waters. Understanding this relationship gives researchers important insights into how the world's oceans may respond to climate change, said Schmittner, a professor in OSU's College of Earth, Ocean, and Atmospheric Sciences.

The ocean plays an important role in the carbon cycle; carbon dioxide from the atmosphere dissolves in surface waters, where algae turn the carbon into organic matter. Respiration of that organic matter removes oxygen as carbon sinks to the deep ocean. The process of transferring carbon from the surface of the ocean to the deep is known as the biological pump.

Currently, the ocean is losing oxygen and that trend is expected to continue because the solubility of oxygen decreases as temperatures warm. That would lead scientists to expect higher oxygen concentrations during the last ice age, when oceans were colder, Schmittner said, but sediment collected previously from below the sea floor shows lower oxygen levels in the deep ocean during that period.

Researchers have previously theorized that the biological pump was stronger during the last ice age, increasing carbon respiration. But that assumes that surface ocean oxygen is equilibrated with the atmosphere, Schmittner said.

In their new work, Schmittner and his colleagues, Ellen Cliff and Samar Khatiwala of the University of Oxford, used modeling to investigate the lower oxygen levels in the deep ocean.

They found that disequilibrium played an important role in the carbon cycle. Deep ocean oxygen concentrations were reduced because surface waters were less equilibrated with the atmosphere. The disequilibrium was a result of the vast sea ice mainly over the Southern Ocean, as well as higher iron fertilization from the ice age atmosphere, which was dustier, Schmittner said.

That means the deep ocean oxygen levels are informed not just by the biological pump process, but also by the sea ice, or lack of, just as a room's air quality may change by the opening or closing of a window, he said.

The researchers' method to understand the role of sea ice and other processes in the ocean carbon and oxygen cycles could also be applied to future climate modeling, Schmittner said.

"Current models cannot separate effects from the biological pump on ocean oxygen from sea ice or other influences," he said. "This changes our understanding of the process and the reasons for those changes."

The lockdowns and reduced societal activity related to the COVID-19 pandemic affected emissions of pollutants in ways that slightly warmed the planet for several months last year, according to new research led by the National Center for Atmospheric Research (NCAR).

The counterintuitive finding highlights the influence of airborne particles, or aerosols, that block incoming sunlight. When emissions of aerosols dropped last spring, more of the Sun's warmth reached the planet, especially in heavily industrialized nations, such as the United States and Russia, that normally pump high amounts of aerosols into the atmosphere.

"There was a big decline in emissions from the most polluting industries, and that had immediate, short-term effects on temperatures," said NCAR scientist Andrew Gettelman, the study's lead author. "Pollution cools the planet, so it makes sense that pollution reductions would warm the planet."

Temperatures over parts of Earth's land surface last spring were about 0.2-0.5 degrees Fahrenheit (0.1-0.3 degrees Celsius) warmer than would have been expected with prevailing weather conditions, the study found. The effect was most pronounced in regions that normally are associated with substantial emissions of aerosols, with the warming reaching about 0.7 degrees F (0.37 C) over much of the United States and Russia.

The new study highlights the complex and often conflicting influences of different types of emissions from power plants, motor vehicles, industrial facilities, and other sources. While aerosols tend to brighten clouds and reflect heat from the Sun back into space, carbon dioxide and other greenhouse gases have the opposite effect, trapping heat near the planet's surface and elevating temperatures.

Despite the short-term warming effects, Gettelman emphasized that the long-term impact of the pandemic may be to slightly slow climate change because of reduced emissions of carbon dioxide, which lingers in the atmosphere for decades and has a more gradual influence on climate. In contrast, aerosols - the focus of the new study - have a more immediate impact that fades away within a few years.

The study was published in Geophysical Research Letters. It was funded in part by the National Science Foundation, NCAR's sponsor. In addition to NCAR scientists, the study was co-authored by scientists at Oxford University, Imperial College, and the University of Leeds.

Teasing out the impacts

Although scientists have long been able to quantify the warming impacts of carbon dioxide, the climatic influence of various types of aerosols - including sulfates, nitrates, black carbon, and dust - has been more difficult to pin down. One of the major challenges for projecting the extent of future climate change is estimating the extent to which society will continue to emit aerosols in the future and the influence of the different types of aerosols on clouds and temperature.

To conduct the research, Gettelman and his co-authors used two of the world's leading climate models: the NCAR-based Community Earth System Model and a model known as ECHAM-HAMMOZ, which was developed by a consortium of European nations. They ran simulations on both models, adjusting emissions of aerosols and incorporating actual meteorological conditions in 2020, such as winds.

This approach enabled them to identify the impact of reduced emissions on temperature changes that were too small to tease out in actual observations, where they could be obscured by the variability in atmospheric conditions.

The results showed that the warming effect was strongest in the mid and upper latitudes of the Northern Hemisphere. The effect was mixed in the tropics and comparatively minor in much of the Southern Hemisphere, where aerosol emissions are not as pervasive.

Gettelman said the study will help scientists better understand the influence of various types of aerosols in different atmospheric conditions, helping to inform efforts to minimize climate change. Although the research illustrates how aerosols counter the warming influence of greenhouse gases, he emphasized that emitting more of them into the lower atmosphere is not a viable strategy for slowing climate change.

"Aerosol emissions have major health ramifications," he said. "Saying we should pollute is not practical."