Culture

As strategies to curb gun violence at the federal level have stalled, leaders in primary care and health policy have identified the role doctors can play in national gun safety efforts and the prevention of firearm suicide. In this pair of recommendation papers, clinicians place themselves at the front lines of this public health issue and offer a call to action for the medical community. Both papers lay out a grassroots course of action to help physicians engage with their patients and policy makers.

Thomas M. Wickizer and colleagues at the Ohio State University focus on the issue of firearm suicide and how improvements in primary care health screening could enhance physicians' ability to identify patients most at risk. Adding firearm safety questions to mental health screening could make firearm safety a more routine part of primary care. The authors also call on collective advocacy for policy change, recognizing the role that physician organizations have historically played in bringing about state-level drunk driving laws and regulation of tobacco advertising. In the wake of gun violence tragedies, physicians have mobilized on social media, using #ThisIsOurLane. The authors believe the medical community can harness the momentum of their online conversations to collectively influence the political discourse on firearms.

Amy Lynn McGuire and colleagues at the Baylor College of Medicine and the Center for Medical Ethics and Health Policy, identify barriers that doctors face in addressing the issue of gun safety and violence with patients. State-level legislation has attempted to prohibit physicians from inquiring about a patient's firearm ownership, resulting in long lasting fears of a "gag order" heightening physicians' concerns over potential liability. Additionally, physicians may be concerned that discussing firearm safety could break the trust they establish in the doctor-patient relationship. The authors advocate that discussions about gun safety and violence become a standard component of routine clinical care to step up the effort to protect public safety and improve public health.

Severe COVID-19 illness can result in excessive inflammation throughout the body, including the lungs, heart and brain. University of Minnesota Twin Cities student Molly Gilligan recently published an article in the journal Cancer & Metastasis Reviews that studied the human body's robust inflammatory response to the SARS-CoV-2 virus, which is now recognized as a hallmark symptom.

According to the publication, controlling the body's inflammatory response to SARS-CoV-2 will likely be as important as antiviral therapies or a potential vaccine. Individual mediators -- called cytokines -- cause inflammation in response to tissue injury or infection. Mediators are a substance or structure that mediates a specific response in a bodily tissue.

Rather than blocking cytokines, medical staff could turn off virus-induced inflammation by broadly activating the body's natural inflammation-clearing activities.

"We are now recognizing the importance of controlling this robust inflammatory response in COVID-19 infection in order to reduce associated organ damage and mortality," said Gilligan, a student at the Medical School. "Finding new ways to dampen the body's inflammatory response to COVID-19 will likely be as important as finding effective antiviral therapies to control COVID-19 infection and reduce life-threatening organ damage."

"Moreover, these compounds have been found to be non-toxic and non-immunosuppressive in ongoing clinical trials for other inflammatory diseases, making them even more promising candidates for rapid clinical translation," said Gilligan.

The research found that:

one hallmark of SARS-CoV-2 infection is a cytokine storm, which is a drastic increase in immune cell production of cytokines;

SARS-CoV-2 causes unchecked inflammation that can cause extensive organ damage, such as lung failure;

current therapeutic strategies in COVID-19 focus on inhibiting a single pro-inflammatory cytokine rather than broadly inhibiting the body's inflammatory response;

lipid mediators derived from omega-3 fatty acids serve as the body's natural "stop" signals to inflammation.

Increasing levels of these lipid mediators in the body could be a new therapeutic approach to preventing life-threatening inflammation caused by SARS-CoV-2.

"What is exciting for us is that these lipid mediators that 'turn off,' or resolve, inflammation are already in clinical trials for other inflammation-driven diseases, such as eye disease, periodontal disease and pain," said Dipak Panigrahy, an assistant professor of pathology in Beth Israel Deaconess Medical Center. "The mediators can quickly be applied to turn off inflammation in COVID-19 patients."

The Comprehensive Primary Care initiative was launched in 2012 by the CMS Innovation Center as a four-year multi-payer initiative designed to strengthen primary care. This study examines shifts in staffing patterns, from 2012 to 2016, at 461 primary care practices participating in the CPC transformation initiative with those at 358 non-CPC practices.

Over the four years of the study, CPC practices moved away from a traditional staffing model of physicians with medical assistants as they added a variety of new staff, most commonly care managers or coordinators and behavioral health staff, to support patients with comprehensive, team-based care. Non-CPC practices, by comparison, did not increase their team size or diversity as much as CPC practices did. For example, in 2016, 84% of CPC practices had care managers or care coordinators, but only 36% of comparison practices had them.

The authors suggest that future studies should examine the effect of team-based care and staff composition on health care cost, service utilization, patient experience and the overall sustainability of new staffing models. In addition, future work should also address how practices make decisions about augmenting staff in response to patients' medical and social needs.

A team of researchers at the University of Göttingen has developed an innovative software program for the simulation of breeding programmes. The "Modular Breeding Program Simulator" (MoBPS) enables the simulation of highly complex breeding programmes in animal and plant breeding and is designed to assist breeders in their everyday decisions. Furthermore, the program is intended to be a cornerstone for further studies in breeding research in Göttingen. In addition to purely economic criteria in breeding, the research team is striving for goals such as sustainability, conservation of genetic diversity and improved animal welfare. The software was presented in the journal G3 Genes, Genomes, Genetics.

"By simulating breeding programmes, conclusions can be drawn about genetic improvements," says Torsten Pook from the Centre for Integrated Breeding Research (Cibreed) at the University of Göttingen. "In fact, potentially problematic issues such as inbreeding or adverse effects on the health of the animals can also be identified at an early stage." Pook is the main developer of MoBPS. The software offers opportunities to realistically model common processes in breeding such as selection, reproduction and data-collection (eg DNA information, trait observations). At the same time, it can simulate millions of matings of animals with certain features in just a few minutes.

"From the simulation of simple maize-breeding programmes, to increased consideration of bone stability in horse breeding, to the simulated development of red deer populations in Baden-Württemberg over the last 200 years, everything has been done," said Pook. The next goal of the research team is to develop an additional module for MoBPS that can automatically optimise breeding programmes with a large number of variables and under given constraints.

You know that feeling when everything suddenly goes quiet? Researchers have identified a novel neural circuit that plays a critical role in processing sound cues of danger to trigger defense responses in rats when silence falls. The study publishing May 12, 2020 in the open-access journal PLOS Biology by Marta Moita of the Champalimaud Centre for the Unknown in Portugal, and colleagues, sheds light on how the brain processes sensory cues and uses this information to generate survival behaviors.

Animals use sound cues produced by others to detect impending danger. Most research has focused on actively emitted signals, such as alarm calls and foot stamping. But rats use a passive signal - silence. When rats feel threatened, they often stop moving, or freeze, in fear.

The silence resulting from this freezing behavior is noticed by other rats, which themselves respond by freezing because they associate the silence of others with danger. But little is known about the neural mechanisms by which natural sounds (or silence) trigger defensive responses. To address this gap in knowledge, Moita and colleagues set out to identify brain regions that are necessary for rats to behave defensively (i.e., freeze) in response to silence, which was induced by the freezing of other rats faced with a threatening situation.

When the researchers separately inactivated three different brain regions, rats became less likely to freeze in response to the silence of other rats exposed to foot shocks. This neural circuit consists of well-established sound-processing brain regions, including the dorsal sub-nucleus of the medial geniculate body, and the ventral area of auditory cortex. In addition, the circuit includes a brain region called the lateral amygdala, which is involved in emotional responses such as fear. This circuit includes brain regions that have not been previously implicated in defense responses. The study provides new insight into the neural mechanisms by which prey animals use the sound of others (or lack thereof) to infer danger and respond defensively.

New Rochelle, NY, May 12, 2020--The impact of COVID-19 on underserved and vulnerable populations, including persons of color, is addressed in a new roundtable discussion in Health Equity, a peer-reviewed open access journal. Click here to read the roundtable now.
The expert panel examines how the COVID-19 crisis has changed the way healthcare is delivered in ways that deepen health inequities. Racial and ethnic biases may also impact decisions about which people are put on ventilators. These populations may also not have as much access to the technology or equipment that enables them to receive remote diagnosis and care. These factors can impact patient recovery and survival greatly.

"This panel discusses the worsening of social burdens on at-risk members of the population and the role of increased implicit bias in health delivery due to time constraints," says Health Equity Editor-in-Chief Ana E. Núñez, MD, Associate Dean for Diversity, Equity and Inclusion and Professor of Medicine, Drexel University School of Medicine, Philadelphia, PA. "When the health care system is already overburdened, how can equity still be on the agenda?"

Researchers at UC Santa Cruz have developed a powerful new computer program called Morpheus that can analyze astronomical image data pixel by pixel to identify and classify all of the galaxies and stars in large data sets from astronomy surveys.

Morpheus is a deep-learning framework that incorporates a variety of artificial intelligence technologies developed for applications such as image and speech recognition. Brant Robertson, a professor of astronomy and astrophysics who leads the Computational Astrophysics Research Group at UC Santa Cruz, said the rapidly increasing size of astronomy data sets has made it essential to automate some of the tasks traditionally done by astronomers.

"There are some things we simply cannot do as humans, so we have to find ways to use computers to deal with the huge amount of data that will be coming in over the next few years from large astronomical survey projects," he said.

Robertson worked with Ryan Hausen, a computer science graduate student in UCSC's Baskin School of Engineering, who developed and tested Morpheus over the past two years. With the publication of their results May 12 in the Astrophysical Journal Supplement Series, Hausen and Robertson are also releasing the Morpheus code publicly and providing online demonstrations.

The morphologies of galaxies, from rotating disk galaxies like our own Milky Way to amorphous elliptical and spheroidal galaxies, can tell astronomers about how galaxies form and evolve over time. Large-scale surveys, such as the Legacy Survey of Space and Time (LSST) to be conducted at the Vera Rubin Observatory now under construction in Chile, will generate huge amounts of image data, and Robertson has been involved in planning how to use that data to understand the formation and evolution of galaxies. LSST will take more than 800 panoramic images each night with a 3.2-billion-pixel camera, recording the entire visible sky twice each week.

"Imagine if you went to astronomers and asked them to classify billions of objects--how could they possibly do that? Now we'll be able to automatically classify those objects and use that information to learn about galaxy evolution," Robertson said.

Other astronomers have used deep-learning technology to classify galaxies, but previous efforts have typically involved adapting existing image recognition algorithms, and researchers have fed the algorithms curated images of galaxies to be classified. Hausen built Morpheus from the ground up specifically for astronomical image data, and the model uses as input the original image data in the standard digital file format used by astronomers.

Pixel-level classification is another important advantage of Morpheus, Robertson said. "With other models, you have to know something is there and feed the model an image, and it classifies the entire galaxy at once," he said. "Morpheus discovers the galaxies for you, and does it pixel by pixel, so it can handle very complicated images, where you might have a spheroidal right next to a disk. For a disk with a central bulge, it classifies the bulge separately. So it's very powerful."

To train the deep-learning algorithm, the researchers used information from a 2015 study in which dozens of astronomers classified about 10,000 galaxies in Hubble Space Telescope images from the CANDELS survey. They then applied Morpheus to image data from the Hubble Legacy Fields, which combines observations taken by several Hubble deep-field surveys.

When Morpheus processes an image of an area of the sky, it generates a new set of images of that part of the sky in which all objects are color-coded based on their morphology, separating astronomical objects from the background and identifying point sources (stars) and different types of galaxies. The output includes a confidence level for each classification. Running on UCSC's lux supercomputer, the program rapidly generates a pixel-by-pixel analysis for the entire data set.

"Morpheus provides detection and morphological classification of astronomical objects at a level of granularity that doesn't currently exist," Hausen said.

An interactive visualization of the Morpheus model results for GOODS South, a deep-field survey that imaged millions of galaxies, has been publicly released. This work was supported by NASA and the National Science Foundation.

Primary care physicians are treating an increasing number of cancer survivors, yet they have no clear guidance on how best to care for such patients. This study considers how primary care physicians perceive their role in delivering care to cancer survivors. The researchers conducted interviews with 38 primary care clinicians and collected data on the 14 practices in which they worked. While most felt cancer survivor care was within their purview, their approaches toward treating cancer survivors varied widely. More broadly, this study brings into question the role of primary care in addressing the complex needs of cancer survivors. Researchers recommend coordinating care between primary care physicians and oncologists as patients transition to long-term survivorship.

RIVERSIDE, Calif. -- A study examining the effect of the immune receptor known as Toll-like Receptor 4, or TLR4, on how memory functions in both the normal and injured brain has found vastly different cellular pathways contribute to the receptor's effects on excitability in the uninjured and injured brain.

Further, the researchers found novel mechanisms for how TLR4 regulates memory function in the normal, uninjured brain.

The study, performed on rats and published in Brain, Behavior, and Immunity, has the potential to lead to treatments aimed at limiting memory deficits after brain injury.

"Memory deficits are a major long-term adverse consequence of brain injury and the ability of a drug treatment given a day after injury to improve memory function is of significant clinical interest," said Viji Santhakumar, an associate professor of molecular, cell and systems biology at the University of California, Riverside, who led the study. "Resatorvid, a drug approved for clinical trials in other diseases, effectively blocked TLR4 and improved post-injury memory deficits in our study."

The brain has neurons and non-neuronal cells called glia. In the normal brain, the activity of neurons is suppressed by TLR4; in the injured brain, TLR4 increases neuronal activity. Specifically, following brain injury, TLR4 increases excitability in the dentate gyrus, a circuit involved in memory processing in the hippocampus, the brain structure that plays a major role in learning and memory.

The UC Riverside-led study found only neurons are involved in TLR4-mediated increase in excitability in the injured brain. In contrast, glial cells are necessary for TLR4-mediated reduction of excitability in the normal brain.

"We found suppressing TLR4 signaling a day after concussive brain injury, common to sports and traffic accidents, reduces excitability and improves working memory performance a week to a month later," she said. "Our data show the processes underlying the damaging effects of brain injury can be selectively manipulated for therapy and can preserve memory function after the injury."

How exactly TLR4 affects memory function in the normal and injured brain is not clear.

"While the actual mechanisms are not known, the speculation is that TLR4 regulates memory function by suppressing neuronal activity in the normal brain, thereby improving signal-to-noise ratio," Santhakumar said. "After injury, the effect of TLR4 flips to enhancing neuronal activity and promoting excitability, which increases noisy and non-specific neuronal firing and degrades signal-to-noise. It is possible that after injury TLR4 impairs cellular processes involved in memory formation, which my lab is currently investigating. The bottom line is that inhibiting TLR4 signaling in the injured brain leads to improvements in long-term working memory deficits for weeks to a month."

Santhakumar was intrigued by a common immune signaling molecule, TNFα, which contributes to both TLR4-dependent reduction in excitability in normal, uninjured brains, and TLR4-mediated increase in excitability after concussive brain injury. In the normal brain, glial cells are involved; in the injured brain, neurons are involved.

"Our study has identified a novel role for neuronal TNFα in regulating excitability," she said. "We were surprised that glial versus neuronal signaling mediated by the same signaling molecule, TNFα, has different effect on neuronal excitability."

Next, Santhakumar and her team plan to determine how TLR4 signaling through glial mediators suppresses network excitability and facilitates memory performance in the normal brain. The researchers also plan to explore how neuronal TLR4 signaling after injury can be selectively manipulated.

"We are interested in determining if blocking TLR4 signaling after injury prevents network reorganization and abnormal changes in rhythmic or oscillatory brain activity that is crucial to memory processing," she said.

Ants use their numbers to overcome navigational challenges that are too large and disorienting to be tackled by any single individual, reports a new study in the open-access journal eLife.

The results demonstrate the potential advantages of group living and collective cognition in making certain environments habitable for a species.

"Cooperation is a common means by which animals can increase their cognitive capacity, and we were intrigued as to whether this cooperation allows ants to extend the range of environments in which they can efficiently collect food," says first author Aviram Gelblum, a postdoctoral fellow in senior author Ofer Feinerman's lab at the Weizmann Institute of Science, Israel. "We addressed this question by studying the cooperative transport of ants as they attempted to transport large loads through semi-natural environments."

A semi-natural labyrinth was created by randomly spreading cubes of the same size across a surface, to mimic a random stone-riddled terrain. Longhorn crazy ants were then tracked while they carried food to a target - their nest - and the coordinates of the food load, the ants and cubes were extracted using image processing. As the number of cubes increased and the maze became more complex, the ants became slower at solving it. They were still able to solve mazes with up to 55% cube coverage, but at 60% coverage most mazes become physically impassable. Importantly, the challenges imposed by the cubes were practically invisible to individual ants that could easily traverse the maze through paths that were blocked for the much larger load.

The team then compared the ants' performance to a well-established model of movement - a random walk that is biased towards a certain direction. In this model, direction is changed in response to the physical feedback of hitting a barrier - in this case, a cube surface - so that eventually the way through is discovered. They found that the ants outperformed the computer model on all but the very simplest cube configurations. The higher the number of cubes in the labyrinth, the better the ants were at solving it compared to the computer model.

To work out how the ants outperformed the computer model, they looked at how the ants spent much longer walking away from the target they were trying to reach. This change in movement could not be explained solely by the physical feedback of encountering a cube. However, it is known that collective movement of ants is guided by leader ants who sense information around the group but do not carry the load.

When the team looked more closely at these non-carrying ants, they found they were spread across a circular region from the carrying population with an outer radius of up to 10cm. Although only a few ants were this far out, even a single leader ant was able to steer the group and guide it as far as 10cm to avoid a physical barrier.

They also noticed that when ants carrying a load got stuck, leader ants constantly presented the carrying group with potential crossing routes. Coordinated movement then allowed the entire group to explore the suggested routes, until they found an escape route that bypassed the obstacle. In this way, the ants were able to extend their sensing range beyond the immediate proximity and, potentially, gain a better idea of the obstacles they were facing.

To see whether this extended sensing was key to solving the labyrinth, the team tested whether this 'sensing' could improve the computer's ability to avoid the cubes. As anticipated, setting the sensing range to match that of the ants allowed the computer model to match the ants' performance in the labyrinth. By contrast, increasing the sensing range to above that of the ants had no effect on the computer's performance, suggesting the ants had worked out the optimal sensing range for that specific maze.

"We have shown that, in this environment, ants use their numbers to collectively extend how far they can sense," concludes senior author Ofer Feinerman, the Henry J. Leir Professorial Chair of the Department of Physics of Complex Systems, Weizmann Institute of Science, Israel. "Although this extension is modest, it allows for extremely fast traversal times that are better than known physical movement models for navigating disordered environments."

A new study by University of Alberta paleontologists shows that one type of ancient reptiles evolved a special type of tooth enamel, similar to that of mammals, with high resistance to wear and tear. The study is the first to report this kind of enamel in a fossil reptile.

The reptile--known as Priosphenodon--was a herbivore from the Late Cretaceous period that was about one metre in length. Part of a group of reptiles called sphenodontians, these reptiles are unique in that they lost their ability to replace individual teeth. Instead, sphenodontians added new teeth to the back ends of their jaws as they grew.

"Priosphenodon has the strangest teeth I have personally ever seen," said Aaron LeBlanc, postdoctoral fellow in the Faculty of Science Department of Biological Sciences and lead author on the study. "Some aspects of their dental anatomy are reminiscent of what happened in the evolution of early mammal teeth."

The specimens were found in Argentina's Río Negro province as part of ongoing collaborative fieldwork and research between Michael Caldwell, professor in the Department of Biological Sciences and the Department of Earth and Atmospheric Sciences, and Argentinian paleontologist and fieldwork leader Sebastián Apesteguía. In order to look more closely at the teeth of Priosphenodon, the researchers cut open pieces of jaw and examined tissue-level detail preserved inside the teeth. They also used non-invasive CT scans to examine more complete jaw specimens.

"Priosphenodon enamel is not only thicker than that of most other reptiles, the enamel crystals are 'woven' into long threads that run through the whole width of the enamel. These threads are called enamel prisms, and they are almost exclusively found in mammals," said LeBlanc, who is working under Caldwell's supervision. "Our results suggest that strong selective pressures can force reptiles to come up with some very innovative solutions to the problems associated with tooth wear and abrasive diets--some of which mirror what happened in our earliest mammal ancestors."

The scientists also note that there is one kind of lizard alive today that has prismatic enamel like Priosphenodon--the spiny-tailed lizard of Australia. Like Priosphenodon, it mostly eats plants and has lost the ability to replace its worn teeth. However, the two reptiles are not closely related.

Collaborators on this study include Sebastián Apesteguía from Universidad Maimónides and the Fundación de Historia Natural Félix de Azara in Buenos Aires, Argentina and Hans Larsson from McGill University in Montreal, Canada. Funding for this research was provided by the Agencia Nacional de Promoción Científica y Tecnológica in Argentina, National Geographic, and Natural Sciences and Engineering Research Council of Canada (NSERC).

The paper, "Unique Tooth Morphology and Prismatic Enamel in Late Cretaceous Sphenodontians from Argentina" was published in Current Biology (doi: 10.1016/j.cub.2020.02.071).

In a new study, Meredith G. F. Worthen, professor of sociology at the University of Oklahoma, and Trenton M. Haltom (Ph.D. candidate, University of Nebraska and OU alumnus) investigate how identifying as a member of the leather community is related to attitudes toward women.

"Because of the widespread attention and misconceptions that came about along with the Fifty Shades books and films, we wanted to better understand the leather/BDSM (bondage, discipline, submission and sadomasochism) community, especially in regards to the treatment of women," said Worthen.

Specifically, they explore leather identity as it relates to the support of laws and policies helping women, non-feminist identity, patriarchal gender norms and the stigmatization of lesbian, bisexual, transgender and queer (LBTQ) women among both hetero and non-hetero (gay, bisexual, pansexual, asexual) leathermen.

Overall, their findings indicated a robust relationship between these anti-woman perspectives and leatherman identity that is especially pronounced among hetero leathermen and demonstrate the importance of continuing to consider how leather identity shapes misogyny among leathermen.

"The leather/BDSM community is often deviantized and marginalized, so it is important to better understand its inner workings, especially because there are so many false and sometimes dangerous perspectives out there," said Haltom. "More research is needed to better cultivate a culture of consent that can encourage the appropriate emotional and psychological pre-negotiations necessary in healthy BDSM relationships that may be newly forming as a result of interest in the Fifty Shades series."

Worthen and Haltom use a nationally representative sample of U.S. adult men ages 18-64 stratified by U.S. Census categories of age, race/ethnicity, and census region (N = 1474) and a subsample of leathermen (n = 65; 58% hetero-leather identified and 42% non-hetero-leather identified). The data were collected using a Faculty Investment Program grant from the OU Vice President for Research that Worthen received in 2018.

To read the full study in Deviant Behavior, visit: https://www.tandfonline.com/doi/full/10.1080/01639625.2020.1762454.

In addition to being a professor at OU, Worthen (@MeredithWorthen) is a researcher and activist who focuses on sociological constructions of deviance and stigma, gender, sexuality and LGBTQ identities, as well as feminist and queer criminology. Her work dissects multiple dimensions of prejudice in an effort to cultivate understanding, empathy and social change. 

Haltom (@TMHaltom) is a Ph.D. candidate in sociology at the University of Nebraska-Lincoln. His research focuses on men's crises of gender and sexuality across media, occupations, health or sports. His dissertation is a mixed-methods content analysis of representations of men's bodies in popular U.S. magazines over time. His research has been published in Gender & Society, Sociology of Sport Journal and in edited volumes.

Children suffering from sickness and diarrhea, coupled with a fever or history of exposure to coronavirus, should be suspected of being infected with COVID-19, recommends a new study published in Frontiers in Pediatrics.

The research also suggests that the gastrointestinal symptoms first suffered by some children hints at potential infection through the digestive tract, as the type of receptors in cells in the lungs targeted by the virus can also be found in the intestines.

"Most children are only mildly affected by COVID-19 and the few severe cases often have underlying health issues. It is easy to miss its diagnosis in the early stage, when a child has non-respiratory symptoms or suffers from another illness," says author of this study, Dr. Wenbin Li, who works at the Department of Pediatrics, Tongji Hospital, Wuhan, China.

He continues, "Based on our experience of dealing with COVID-19, in regions where this virus is epidemic, children suffering from digestive tract symptoms, especially with fever and/or a history of exposure to this disease, should be suspected of being infected with this virus."

In this study, Li and his colleagues detail the clinical features of children admitted to hospital with non-respiratory symptoms, which were subsequently diagnosed with pneumonia and COVID-19.

"These children were seeking medical advice in the emergency department for unrelated problems, for example, one had a kidney stone, another a head trauma. All had pneumonia confirmed by chest CT scan before or soon after admission and then confirmed to have COVID-19. While their initial symptoms may have been unrelated, or their COVID-19 symptoms were initially mild or relatively hidden before their admission to hospital, importantly, 4 of the 5 cases had digestive tract symptoms as the first manifestation of this disease."

By highlighting these cases, Li hopes that doctors will use this information to quickly diagnose and isolate patients with similar symptoms, which will aid early treatment and reduce transmission.

The researchers also link the children's gastrointestinal symptoms, which have been recorded in adult patients, to an additional potential route of infection.

Li explains, "The gastro-intestinal symptoms experienced by these children may be related to the distribution of receptors and the transmission pathway associated with COVID-19 infection in humans. The virus infects people via the ACE2 receptor, which can be found in certain cells in the lungs as well as the intestines. This suggests that COVID-19 might infect patients not only through the respiratory tract in the form of air droplets, but also through the digestive tract by contact or fecal-oral transmission."

While COVID-19 tests can occasionally produce false positive readings, Li is certain all these five children were infected with the disease, but he cautions that more research is needed to confirm their findings.

"We report five cases of COVID-19 in children showing non-respiratory symptoms as the first manifestation after admission to hospital. The incidence and clinical features of similar cases needs further study in more patients."

LOS ANGELES -- Four of six critically ill COVID-19 (coronavirus) patients significantly improved after receiving an experimental therapeutic designed to reduce inflammation, a major cause of death from this disease, according to a case series published by Cedars-Sinai and Capricor Therapeutics. The four patients got well enough to be discharged from the hospital.

The therapeutic, known as CAP-1002, contains cardiosphere-derived cells (CDCs) that are grown in the laboratory from human heart tissues. Previous preclinical and clinical research showed that the CDCs, originally created by a process developed to treat heart failure, can help the whole body.

Investigators emphasized that the patient outcomes, while encouraging, are not sufficient to prove that CAP-1002 is safe and effective for treating COVID-19 because this was not a clinical trial with a control group.

The case series, published today in the scientific journal Basic Research in Cardiology, is believed to be the first peer-reviewed report on using a cell therapy in critically ill COVID-19 patients, according to Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai.

All six patients in the case series suffered from respiratory failure and required supplemental oxygen prior to receiving the cell therapy; five were on ventilators. Within four days after infusion with CAP-1002, four patients were able to breathe without respiratory support, and within less than three weeks, the four were well enough to be discharged from the hospital. As of April 28, the two other patients remained hospitalized in intensive care.

None of the patients showed adverse effects from the infusions, and none died during the study period. By comparison, six patients died among a group of 34 comparable COVID-19 patients who were treated in Cedars-Sinai's intensive care unit around the same time but who did not receive the cell therapy.

The patients in the case series were treated at Cedars-Sinai under emergency use provisions, which allows use of therapies not yet approved by the Food and Drug Administration to treat seriously ill patients when no other treatments are available.

"Previous studies provided strong evidence that CDCs have intense benefits for the immune system and inflammation in a number of diseases," Marbán explained, "They accomplish this by secreting exosomes- nanoscale vesicles with a variety of active contents that travel widely throughout the body."

Marbán said this anti-inflammatory effect could be a critical boost for coronavirus patients. Current information, he explained, indicates that the body's overreaction to the COVID-19 infection, rather than the virus itself, often delivers the fatal blow, especially in later stages of the disease.

"'Friendly fire' is what's killing many coronavirus patients," said Marbán, professor of Cardiology and co-author. "The immune system unleashes a so-called cytokine storm into the blood-overwhelming the body with infection-fighting proteins that can trigger multiple-organ failure and death."

Raj Makkar, MD, the principal author, said the investigative team is planning a future clinical trial that would involve dividing a larger number of coronavirus patients into two groups: those who receive the therapy and a control who do not. The team would then compare the outcome for the two groups.

"The only way to establish the efficacy of our therapy is with a randomized clinical trial," Makkar said. "That is because some coronavirus patients get better on their own with standard treatments."

Makkar added that if the CDCs counteract immune overreaction in coronavirus patients, the cells potentially could help prevent or treat two other life-threatening conditions that often develop during the course of the disease: acute respiratory distress and inflammation of the heart muscle, known as myocarditis.

The emergency use treatment was conducted in collaboration with the biotechnology company Capricor Therapeutics in Los Angeles, which provided regulatory support and manufactured the experimental agent (CAP-1002).

Scientists worldwide have long debated our ability to identify male and female dinosaurs. Now, research led by Queen Mary University of London has shown that despite previous claims of success, it's very difficult to spot differences between the sexes.

In the new study, researchers analysed skulls from modern-day gharials, an endangered and giant crocodilian species, to see how easy it is to distinguish between males and females using only fossil records.

Male gharials are larger in size than females and possess a fleshy growth on the end of their snout, known as a ghara. Whilst the ghara is made from soft tissue, it is supported by a bony hollow near the nostrils, known as the narial fossa, which can be identified in their skulls.

The research team, which included Jordan Mallon from the Canadian Museum of Nature, Patrick Hennessey from Georgia Southern University and Lawrence Witmer from Ohio University, studied 106 gharial specimens in museums across the world. They found that aside from the presence of the narial fossa in males, it was still very hard to tell the sexes apart.

Dr David Hone, Senior Lecturer in Zoology at Queen Mary University of London and author of the study, said: "Like dinosaurs, gharials are large, slow growing reptiles that lay eggs, which makes them a good model for studying extinct dinosaur species. Our research shows that even with prior knowledge of the sex of the specimen, it can still be difficult to tell male and female gharials apart. With most dinosaurs we don't have anywhere near that size of the dataset used for this study, and we don't know the sex of the animals, so we'd expect this task to be much harder."

In many species, males and females can look very different from each other. For example, antlers are largely only found in male deer and in peacocks, males are normally brightly-coloured with large, iridescent tail feathers whereas females are much more subdued in their colouration. This is known as sexual dimorphism and is very common within the animal kingdom. It is expected that dinosaurs also exhibit these differences, however this research suggests that in most cases this is far too difficult to tell from the skeleton alone.

Dr Hone said: "Some animals show extraordinarily high levels of sexual dimorphism, for example huge size differences between males and females. Gharials sit somewhere in the middle as they do possess these large narial fossa that can help with identification. Our study suggests that unless the differences between the dinosaurs are really striking, or there is a clear feature like the fossa, we will struggle to tell a male and female dinosaur apart using our existing dinosaur skeletons."

The new research also challenges previous studies that have hinted at differences between the sexes in popular dinosaur species such as the Tyrannosaurus rex (T. rex), and led to common misconceptions amongst the general public.

"Many years ago, a scientific paper suggested that female T. rex are bigger than males. However, this was based on records from 25 broken specimens and our results show this level of data just isn't good enough to be able to make this conclusion," Dr Hone added.