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ROCHESTER, Minn. ? Using data from 9,859 COVID-19 infections, Mayo Clinic researchers have new insights into risk factors for younger populations, some of which differ significantly from their older counterparts. People younger than 45 had a greater than threefold increased risk of severe infection if they had cancer or heart disease, or blood, neurologic or endocrine disorders, the research found. These associations were weaker in older age groups. The study was published in Mayo Clinic Proceedings.

The research team studied people living in a 27-county region of Southeast Minnesota and West Central Wisconsin surrounding Mayo Clinic in Rochester diagnosed with COVID-19 between March and September 2020. The study used the Rochester Epidemiology Project, a linkage of 1.7 million medical records from multiple health care systems that provides a full picture of risks for an entire geographical region.

"Medical care is really fragmented in our country, so someone diagnosed with COVID-19 at one health care provider might end up at a totally different hospital for their severe case. If those records are not linked together, there's really not a good way for us to understand that that is even the same patient," says Jennifer St. Sauver, Ph.D., a Mayo Clinic epidemiologist and the study's first author. "By contrast, the Rochester Epidemiology Project allowed us to follow patients from the time they were diagnosed through their use of health care after that diagnosis, even if they were taken care of at different places. In addition, we could look back in their medical records to better understand all of the chronic diseases this population had even before getting diagnosed with COVID-19 and how those diseases might have contributed to more severe infections."

Among study participants, cancer was the biggest difference in risk comparing people younger and older than 45. For people younger than 45, cancer was a strong risk factor. It was not a significant factor for the older age group.

The researchers also found that people with developmental disorders, personality disorders, schizophrenia and other psychoses had the highest adjusted risk for severe COVID-19 among all chronic conditions.

Like many other studies on risk factors for COVID-19, the researchers found some races and ethnicities were at a higher risk than others. Though only 4.1% of the study population, Asian Americans had the highest risk of severe COVID-19, followed by Black Americans, who made up 11.5% of the severe cases. Hispanic ethnicity also was associated with a higher risk of severe infection.

The team studied positive PCR (polymerase chain reaction) tests for COVID-19 between March 1 and Sept. 30, 2020.

The COVID in our Community Research Study is being conducted by Mayo Clinic, Olmsted County Public Health Services, Olmsted Medical Center, and Zumbro Valley Health Center. The researchers say the project would not have been possible without the Rochester Epidemiology Project.

"The Rochester Epidemiology Project allows us to study diseases, such as COVID-19, in a defined population, which provides the ability to translate our results to all people with COVID-19, not just those with the most severe disease requiring medical care," says senior author Celine Vachon, Ph.D., Chair of the Mayo Clinic Division of Epidemiology. "This type of infrastructure will allow us to follow patients who had COVID-19 in the 27-county region over time to better understand any future links to disease."

An international team of researchers led by Kumamoto and Tokyo Universities (Japan) have shown that the L452R mutation of the SARS-CoV-2 spike protein, which is common to two mutant strains (Epsilon and Delta), is involved in cellular immunity evasion via the human leukocyte antigen (HLA) A24, and enhances viral infectivity. HLA-A24 is one of the most prominent HLA-class I alleles, especially in East/Southeast Asian populations, which might make them particularly vulnerable to coronavirus variants with this mutation.

The ongoing novel coronavirus (SARS-CoV-2 or COVID-19) pandemic has, as of June 2021, infected over 150 million and killed over 3.5 million people worldwide. Vaccination drives around the world are currently underway, but there are still many unknowns, including the principles of infection pathogenesis, the principles viral replication, and the relationship between immune evasion and epidemic dynamics.

Acquired immunity can be broadly classified into humoral immunity mediated by neutralizing antibodies and cellular immunity mediated by helper and killer T cells. SARS-CoV-2 "variants of concern", such as the Alpha and Beta variants, have been studied worldwide for the possibility of humoral immunity evasion. However, cellular immunity evasion has not been reported.

In this study, the research group first used immunological experiments to demonstrate that an antigen derived from the SARS-CoV-2 spike protein is strongly recognized by HLA-A24-restricted cellular immunity, which is often found in Japanese people. They then performed a large-scale (>750,000) sequence analysis of SARS-CoV-2 strains and found several important mutations in the spike protein region typically recognized by HLA-A24. These are the Y453F spike mutations found in strain B.1.1.298, which was prevalent in Denmark in 2020, and the L452R mutation in B.1.427/429 and B.1.617 (commonly known as the Epsilon and Delta variants respectively) that are currently spreading around the world. Further immunological experiments demonstrated that these mutations escape HLA-A24 cellular immunity. The researchers believe that this is the first time a "variant of concern" has been demonstrated to evade cellular immunity.

The Y453F and L452R mutations were located in the receptor binding domain of the SARS-CoV-2 spike protein, which are crucial for gaining entry into host cells. Researchers thus examined the effects of these mutations on the infection and replication efficiency of the virus. They found that the L452R mutation enhances its membrane fusion activity, infectivity, and viral replication.

"The L452R mutation is a hallmark of the Delta variant that is currently spreading worldwide, and in Japan, about 60% of the population have HLA-A24, which is responsible for cellular immunity. The L452R mutation not only evades the HLA-A24 cellular immunity but can also enhance the infectivity of the virus," said the leader of immunology in the study, Dr. Chihiro Motozono." We have been carefully investigating the immune response against emerging SARS-CoV-2 variants in real time to monitor how the mutations affect human immunity and viral infectivity."

CT scans for patients with concussion provide critical information about their risk for long-term impairment and potential to make a complete recovery - findings that underscore the need for physician follow-up.

In a study led by UC San Francisco, researchers looked at the CT scans of 1,935 patients, ages 17 and over, whose neurological exams met criteria for concussion, or mild traumatic brain injury (TBI), at hospitals throughout the nation. While links between CT imaging features and outcome have already been established in moderate and severe TBI, the researchers believe this is the first time the link has been identified in patients with concussion, disputing earlier research that found no prognostic significance of specific types of CT abnormalities.

"Radiologists who routinely read trauma scans know intuitively that patterns of intracranial injury on CT are not random," said first author, Esther Yuh, MD, PhD, of the UCSF Department of Radiology and Biomedical Imaging. "We showed there are patterns of injury, that some of these are associated with worse outcome than others, and that they provide a window into mechanisms of injury that is reproducible across large studies."

The study appears online in JAMA Neurology on July 19, 2021.

"Although concussions are referred to as mild traumatic brain injuries, there is nothing mild about some concussions," said senior author Geoffrey Manley, MD, PhD, professor and vice chair of neurological surgery at UCSF and chief of neurosurgery at Zuckerberg San Francisco General Hospital. "Patients with concussion may suffer from prolonged headache, poor sleep and impaired concentration, and they are at higher risk of self-medicating with drugs and alcohol. Concussion can also contribute to depression and anxiety, and increase the risk for suicide. We need to view concussion not as an event but as a disease requiring physician follow-up after a patient is discharged from the hospital."

The participants were enrolled by the brain injury research initiative TRACK-TBI, of which Manley is the principal investigator. To enrich the number of so-called complicated concussions, the researchers drew exclusively from patients who had been seen at hospitals with level 1 trauma centers. This meant 37 percent of study participants had a positive CT, significantly more than the 9 percent of positive CTs from patients in U.S. emergency departments.

Baseball Whacks May Have Better Outcomes than Other Injuries

The most common patterns of injury, affecting more than half of CT-positive patients, were combinations of subarachnoid hemorrhage (SAH), subdural hematoma (SDH), and/or contusion, which may be caused by injuries such as falls from standing. Approximately 7 percent had intraventricular hemorrhage (IVH) or petechial hemorrhage, caused by rotation of the head, occurring in some sporting, scooter and automobile accidents; and 5 percent were found to have epidural hematoma (EDH) in which blood accumulates between the skull and the membrane covering the brain, often seen in sports injuries such as being hit with a baseball.

The patients, whose average age was 41 and of whom 66 percent were male, were assessed at two weeks, and at three-, six- and 12 months following injury. The researchers found that patients in the SAH/SDH/contusion group failed to make a complete recovery at 12 months post-injury and had impairments across the outcome spectrum, from mild to more severe.

Patients in the IVH/petechial hemorrhage group tended toward more severe impairments, in the lower-moderate disability range, a level that potentially affects multiple areas of function, such as employment, social and leisure activities, up to 12 months post-injury. Patients with the EDH phenotype fared significantly better and demonstrated complete recovery by their six-month assessment.

Results of the study were validated by CENTER-TBI, a parallel brain injury research group that had enrolled 2,594 participants at European trauma centers. "The confirmation of the findings in an independent cohort confirms the fidelity of our results," said Manley, adding that patients with EDH were one exception. CENTER-TBI found their incomplete recovery lingered for months longer than those patients followed by TRACK-TBI, but more severe outcomes were not seen at any point in either study.

The researchers noted that even among concussion patients who had a positive CT scan, just 39 percent receive follow-up care, including simple interventions like providing educational material at discharge. Follow-up should be routine for all 5 million concussion patients seen annually in the nation's emergency departments, including those without abnormal CT features, who would have milder symptoms and more complete recoveries, they said.

Test for Blood-Markers is Safer, More Sensitive

The researchers cautioned that these results should not be interpreted as a call to increase the use of CT, which exposes patients to radiation and increases cancer risk. Currently CTs are recommended for patients with a known or suspected concussion and loss of consciousness or amnesia and/or factors like older age, evidence of physical trauma and severe headache.

In fact, CTs may become less widely used with the recent approval by the Food and Drug Administration of a rapid hand-held blood test that Manley found was more sensitive than CT in detecting concussion. The blood test measures biomarkers associated with TBI, which were close to 52 times higher in concussion patients than in healthy participants when verified by MRI, a more definitive but costlier and less accessible scan than CT.

In addition to challenging the belief that CT features in concussion are not relevant, the researchers are also challenging the idea that concussion is "what the patient brings to the injury," said Manley, who is also affiliated with the UCSF Weill Institute for Neurosciences. "In moderate and severe TBI, it is anecdotally taught that outcome is determined by 'what the injury brings to the patient,' while concussion is determined by baseline characteristics like age, sex and years of education. While the study confirms the importance of these characteristics, we show that in some concussion cases, poor outcomes are also attributed to 'what the injury brings to the patient.'"

What The Study Did: This study investigated the association between time spent cycling and the risk of death from cardiovascular disease or any other cause among people with diabetes.

Authors: Mathias Ried-Larsen, Ph.D., of Rigshospitalet in Copenhagen, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.3836)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study and editor's note are linked to this news release.

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What The Study Did: The association between daily coffee consumption and the risk of cardiac arrhythmias was evaluated in this study.

Authors: Gregory M. Marcus, M.D., M.A.S., of the University of California, San Francisco, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.3616)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Media advisory: The full study and commentary are linked to this news release.

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What The Study Did: This study included a meta-analysis that combined the results of 74 studies with 2.7 million participants to estimate how common globally dementia is in people younger than age 65.

Authors: Sebastian Köhler, Ph.D., of Maastricht University in Maastricht, the Netherlands, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaneurol.2021.2161)

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A major drought and forest fires in the Amazon rainforest killed billions of trees and plants and turned one of the world's largest carbon sinks into one of its biggest polluters.

Triggered by the 2015-16 El Niño, extreme drought and associated mega-wildfires caused the death of around 2.5 billion trees and plants and emitted 495 million tonnes of CO2 from an area that makes up just 1.2 per cent of the entire Brazilian Amazon rainforest, and 1 per cent of the whole biome.

The stark findings, discovered by an international team of scientists working for more than eight years on a long-term study in the Amazon before, during and after the El Niño, have significant implications for global efforts to control the atmospheric carbon balance.

In normal circumstances, because of high moisture levels, the Amazon rainforest does not burn. However, extreme drought makes the forest temporarily flammable. Fires started by farmers can escape their land and trigger forest fires.

According to climate predictions, extreme droughts will become more common and, until now, the long-term effects of drought and fires on the Amazon rainforest, and particularly within forests disturbed by people through activities such as selective or illegal logging, were largely unknown.

Examining the Amazonian epicentre of the El Niño - Brazil's Lower Tapajós, an eastern Amazonia area around twice the size of Belgium - the research team, led by scientists from Lancaster University, the University of Oxford, and The Brazilian Agricultural Research Corporation found the damage lasts for multiple years.

The study revealed that trees and plants in drought-affected forests, as well as burned forests, continued to die at a rate above the norm for up to three years after the El Niño drought - releasing more CO2.into the atmosphere.

The total carbon emissions from the drought and fires in the Lower Tapajós region alone were higher than a whole year's deforestation within the entire Amazon. And, as a result of the drought and fires, the region released as much over a three-year period as some of the world's worst polluting countries' yearly carbon emissions - exceeding the emissions of developed countries such as the UK and Australia.

After three years, only around a third (37%) of the emissions were re-absorbed by plant growth in the forest. This shows that the Amazon's vital function as a carbon sink can be hampered for years following these drought events.

Dr Erika Berenguer, lead author of the report from Lancaster University and the University of Oxford, said: "Our results highlight the enormously damaging and long-lasting effects fires can cause in Amazonian forests, an ecosystem that did not co-evolve with fires as a regular pressure."

The scientists gathered data by regularly revisiting 21 plots across a mixture of primary forest, secondary re-growing forest and forests where people have selectively logged. The results from these plots were then extrapolated to the region.

Although previous research has shown human-disturbed forests are more susceptible to fires, it was unknown if there was any difference in the vulnerability and resilience of trees and plants in these forests when drought and fires happen.

The study showed that while many trees died in primary forest affected by drought, the loss of trees was much worse in secondary and other human-disturbed forests. The researchers found that trees and plants with lower wood density and thinner barks were more prone to dying from the drought and fires. These smaller trees are more common in human-disturbed forests.

The researchers estimate that around 447 million large trees (greater than 10cm Diameter at Breast Height) died, and around 2.5 billion smaller trees (less than 10cm DBH) died across the Lower Tapajós region.

The researchers also compared the effect on different forest types from drought alone, as well as the combined stresses of drought and fire.

Tree and plant mortality was higher in secondary forests from drought alone when compared with primary forests. Impact from drought was not higher in human-modified forests, but was significantly greater in those human-modified forests that experienced a combination of drought and fire.

Carbon emissions from those forests burned by wildfires were almost six times higher than forests affected by drought alone.

These findings highlight how interference by people can make the Amazon forests more vulnerable and underline the need to reduce illegal logging and other large-scale human disturbances of forests in the Amazon, as well as investments in fire-fighting capabilities in the Amazon.

Professor Jos Barlow of Lancaster University and the Universidade Federal de Lavras, and Principal Investigator of the research, said: "The results highlight the need for action across different scales. Internationally, we need action to tackle climate change, which is making extreme droughts and fires more likely. At the local level, forests will suffer fewer negative consequences from fires if they are protected from degradation."

An international team anchored by the Event Horizon Telescope (EHT) Collaboration, which is known for capturing the first image of a black hole in the galaxy Messier 87, has now imaged the heart of the nearby radio galaxy Centaurus A in unprecedented detail. The astronomers pinpoint the location of the central supermassive black hole and reveal how a gigantic jet is being born. Most remarkably, only the outer edges of the jet seem to emit radiation, which challenges our theoretical models of jets. This work, led by Michael Janssen from the Max Planck Institute for Radio Astronomy in Bonn and Radboud University Nijmegen is published in Nature Astronomy on July 19th.

At radio wavelengths, Centaurus A emerges as one of the largest and brightest objects in the night sky. After it was identified as one of the first known extragalactic radio sources in 1949, Centaurus A has been studied extensively across the entire electromagnetic spectrum by a variety of radio, infrared, optical, X-ray, and gamma-ray observatories. At the center of Centaurus A lies a black hole with the mass of 55 million suns, which is right between the mass scales of the Messier 87 black hole (six and a half billion suns) and the one in the center of our own galaxy (about four million suns).

In a new paper in Nature Astronomy, data from the 2017 EHT observations have been analyzed to image Centaurus A in unprecedented detail. "This allows us for the first time to see and study an extragalactic radio jet on scales smaller than the distance light travels in one day. We see up close and personally how a monstrously gigantic jet launched by a supermassive black hole is being born", says astronomer Michael Janssen.

Compared to all previous high-resolution observations, the jet launched in Centaurus A is imaged at a tenfold higher frequency and sixteen times sharper resolution. With the resolving power of the EHT, we can now link the vast scales of the source, which are as big as 16 times the angular diameter of the Moon on the sky, to their origin near the black hole in a region of merely the width of an apple on the Moon when projected on the sky. That is a magnification factor of one billion.

Understanding jets

Supermassive black holes residing in the center of galaxies like Centaurus A are feeding off gas and dust that is attracted by their enormous gravitational pull. This process releases massive amounts of energy and the galaxy is said to become 'active'. Most matter lying close to the edge of the black hole falls in. However, some of the surrounding particles escape moments before capture and are blown far out into space: Jets - one of the most mysterious and energetic features of galaxies - are born.

Astronomers have relied on different models of how matter behaves near the black hole to better understand this process. But they still do not know exactly how jets are launched from its central region and how they can extend over scales that are larger than their host galaxies without dispersing out. The EHT aims to resolve this mystery.

The new image shows that the jet launched by Centaurus A is brighter at the edges compared to the center. This phenomenon is known from other jets, but has never been seen so pronouncedly before. "Now we are able to rule out theoretical jet models that are unable to reproduce this edge-brightening. It's a striking feature that will help us better understand jets produced by black holes", says Matthias Kadler, TANAMI leader and professor for astrophysics at the University of Würzburg in Germany.

The oil industry, pharmaceutical companies and bioreactor manufacturers all face one common enemy: bubbles. Bubbles can form during the manufacturing or transport of various liquids, and their formation and rupture can cause significant issues in product quality.

Inspired by these issues and the puzzling physics behind bubbles, an international scientific collaboration was born. Stanford University chemical engineer Gerald Fuller along with his PhD students Aadithya Kannan and Vinny Chandran Suja, as well as visiting PhD student Daniele Tammaro from the University of Naples, teamed up to study how different kinds of bubbles pop.

The researchers were particularly interested in bubbles with proteins embedded on their surfaces, which is a common occurrence in the pharmaceutical industry and in bioreactors used for cell culture. In an unanticipated result, the researchers discovered that the protein bubbles they were studying opened up like flowers when popped with a needle. Their findings are detailed in a study published in the journal of the Proceedings of the National Academy of Sciences on July 19.

"What really strikes me is that even after all these years of research, bubble physics keeps surprising us with unexpectedly beautiful phenomena," Suja said.

Bursting the bubble

Bubbles can pop in a variety of ways, depending on their physical and chemical properties. One important property is called viscoelasticity.

"Most materials that surround us are actually not perfectly liquid like water or olive oil. They're not perfectly elastic either, like a pencil eraser. They're somewhere in between," explained Fuller, who is the Fletcher Jones II Professor in the School of Engineering and co-led the study with Professor Pier Luca Maffettone from the University of Naples.

This "in-between" state is called viscoelasticity, and the researchers found that, unlike conventional soap bubbles, viscoelastic bubbles that have both liquid- and solid-like properties deform and pop in shapes that mimic a blooming flower.

But as Tammaro notes, "With our eyes it's not possible to see how the hole opens up when a bubble pops, so we just see a bubble that vanishes."

So the researchers used high-speed cameras operating at 20,000 frames per second, over 300 times faster than a human eye, to capture and study the phenomenon.

"While working on my thesis on bubble coalescence in biologic drug formulations, I decided to look at bubble rupture through a high-speed camera that we had in our lab," Kannan said. "When we did that, we saw that this bubble, which had proteins at its surface, actually exhibited a very different mechanism of rupture compared to what we traditionally expect."

In the lab, the researchers soaked a metal ring in a solution of proteins with viscoelastic properties. They then carefully inflated bubbles on this ring using a highly controlled flow of air. Once the bubbles were large enough, they made contact with a suspended needle and popped.

As the video shows, when the bubbles reach the needle, the surface peels away like petals. This peeling happens because the viscoelastic properties at the surface allow the solution to have more solid-like characteristics than common soap bubbles. Kannan likened this special bubble bursting to a popping balloon, which also peels away like a flower.

Investigating bubble physics

Once the flowering phenomenon had been sufficiently observed, the researchers began to develop analytical models of the popping. Using current knowledge of bubble dynamics and mathematical models, the team presented a set of promising computational reproductions of the bubble flowering in their paper.

By studying bubble formation and bursting, the team hopes to eventually learn how to reduce bubble generation and popping in real-world applications. They predict that their findings will have applications in fields from medicine and vaccine production to oil transportation.

"It is really important to see how generalizable this is, and how the flowering is different for other systems," Kannan concluded.

New research has found marine seismic surveys used in oil and gas exploration are not impacting the abundance or behaviour of commercially valuable fishes in the tropical shelf environment in north-western Australia.

The research is the first of its kind to use dedicated seismic vessels to measure the impacts of the survey's noise in an ocean environment, with the eight-month experiment conducted within a 2500 square kilometre fishery management zone near the Pilbara coast.

It involved using multiple acoustic sensors, tagging 387 red emperor fish and deploying more than 600 underwater cameras to track and measure fish behaviour before and after firing seismic air guns into the ocean.

Australian Institute of Marine Science (AIMS) Principal Researcher and project leader Dr Mark Meekan said the large-scale experiment measured the short-term and long-term effects of seismic airguns on the community of commercially important species in the region, such as red emperor (Lutjanus sebae).

"What makes this research unique and robust is we used an actual seismic vessel in a real ocean environment and some of the most advanced technologies to track and measure possible impacts," he said.

"Commercial fishers are concerned seismic survey noise could change the abundance and behaviour of key fish species - this research directly sought to determine if commercially valuable fish leave the area or hide when exposed to the seismic noise.

"The results reveal there were no short-term or long-term effects on the abundance, behaviour and movement of bottom-living fishes.

"This suggests seismic surveys have little impact on commercially valuable fish species in this environment."

AIMS acoustic scientist and co-author Dr Miles Parsons said Baited Remote Underwater Video Systems (BRUVS) were deployed to document the movements, feeding patterns and abundance of the entire benthic fish community.

Red emperor fish - an important target of fisheries - were tagged and tracked via an array of acoustic telemetry receivers to understand their movements.

"It was surprising to find no changes in the key behaviours we were assessing after the fish were exposed to seismic blasts," he said.

This research fills in a key knowledge gap in the effect of seismic exploration on fisheries in the area, which is necessary for managers, marine industries, and policy makers to make informed decisions about its sustainable use.

"The magnitude and extent of this study also means the results provide valuable knowledge on potential impacts in other environments, not just in Australia, but internationally."

The research experiment is part of the North West Shoals to Shore Research Program. The program also investigates impacts on pearl oysters, with this study still in progress.

The struggle to get your child to go to sleep and stay asleep is something most parents can relate to. Once the bedtime battle is over and the kids have finally nodded off, many parents tune out as well.

But University of South Australia researcher Professor Kurt Lushington is calling for parents to check on their small snoozers before switching off.

He says knowing the quality of a child's sleep is important, as it could be an indicator of sleep-disordered breathing - an under-reported medical condition that can affect a child's health and wellbeing.

"During sleep, the muscles keeping the upper airway stiff relax, and as a consequence, the airway narrows, which can cause snoring, snorting or in severe cases, the complete obstruction of the airway," Prof Lushington says.

"This is known as sleep-disordered breathing, which can lead to a number of problems for children including daytime sleepiness, fatigue, irritability, hyperactivity and poor attention - and potentially worsens school performance.

"The long-term effects are not well understood but research suggests sleep-disordered breathing could also impair cardiovascular and metabolic health.

"Sleep-disordered breathing is significantly undiagnosed in the community. Parents can play an important role in the diagnostic process by looking out for the common symptoms, which include heavy breathing, snoring, gasping, or snorting, and stopping breathing altogether - and then share that information with their child's doctor."

In a new study of 1639 children in South Australia, Prof Lushington and colleagues surveyed parents to gauge whether they saw sleep-disordered breathing symptoms as a sleep problem. The findings suggest many parents do hold concerns about their children's sleeping habits, but it doesn't translate to them seeking medical help.

Almost all parents of children with sleep-disordered symptoms viewed apnoea as a problem while nearly two-thirds saw snorting, gasping, and being fearful their child would stop breathing as a problem.

Roughly half of parents considered snoring a problem and only one third viewed breathing heavily but not snoring as an issue.

Prof Lushington says the results are surprising given that most parents don't bring up these concerns with their child's medical professionals.

"Parents don't tend to discuss their child's sleep difficulties at medical consultations - in Australia, it's estimated only four per cent of parents will bring this up with their doctor," he says.

"The good news from our study is that we found that many parents are already recognising that there is a sleep problem. Prior to this, we had hypothesised that the under-reporting of symptoms suggestive of sleep-disordered breathing, or of sleep problems in general, at medical consultation could be because of the lack of parents' awareness of a problem existing.

"While there does need to be more education for parents on symptoms of sleep-disordered breathing - particularly around snoring or heavy breathing being a potential cause for concern, there are clearly other barriers to parents bringing up sleep problems in medical consultations.

"To address this, we suggest medical practitioners need to purposely include questions about sleep at consultations to prompt parents to discuss any symptoms they may have observed in their children at night.

"If parents check in to see how well their children are sleeping at night and doctors routinely check in with parents to discuss children's sleeping habits, we might be able to catch sleep-disordered breathing earlier and take steps to treat it before it affects a child's behaviour and health."

The current treatment for sleep-disordered breathing in children is adenotonsillectomy - the removal of adenoid and tonsils - which is known to improve children's quality of life and sleep.

The research was published in the paper 'Sleep disordered breathing in children: which symptoms do parents consider a problem?' in the Sleep Medicine.

Your child's sleep - tips for checking in:

Familiarise yourself with guidelines advising how much sleep children need at different ages to function well during the day.

If your child is getting enough sleep according to the guidelines but experiences daytime problems with sleepiness, fatigue, irritability, hyperactivity, or poor attention, this could be a sign of sleep-disordered breathing.

If you notice your child snores, struggles to breath at night, has long pauses between breaths greater than 20 seconds, or gasps at night - it's time to bring up the symptoms with your child's GP or paediatrician.

Educate yourself on what normative sleep is to make sure everyone in your household is getting a good night's sleep - the Sleep Health Foundation is a great starting point with a number of fact sheets freely available online.

The July issues of two of the American Psychiatric Association journals, The American Journal of Psychiatry and Psychiatric Services are available online.

The American Journal of Psychiatry is the most widely read psychiatric journal in the world. Its July issue offers a collection of articles discussing the impacts of structural racism, socioeconomic deprivation and stigmatization on mental health. This includes the article From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States, which was featured at the APA Annual Meeting in May. Among other highlights:

Dismantling Structural Racism in Psychiatry: A Path to Mental Health Equity

Modification of Heritability for Educational Attainment and Fluid Intelligence by Socioeconomic Deprivation

Sustained Effect of a Brief Video in Reducing Public Stigma Toward Individuals With Psychosis

Association Between Benzodiazepine or Z-Drug Prescriptions and Drug-Related Poisonings Among Patients Receiving Buprenorphine Maintenance

"I am very excited about this issue of the Journal as it presents papers that are fundamental to understanding how structural racism negatively impacts our patients and the field of psychiatry," said American Journal of Psychiatry Editor-in-Chief Ned H. Kalin, M.D. "Our Editors and Editorial Board are committed to using the Journal to combat the effects of structural racism, social injustices, and other inequities on mental health and well-being and this is an important step in that direction."

Psychiatric Services, established in 1950, features research reports on issues related to the delivery of mental health services, especially for people with serious mental illness in community-based treatment programs. Its July issue features:

The Role of Board-Certified Psychiatric Pharmacists in Expanding Access to Care and Improving Patient Outcomes

Community Inclusion and Social Determinants: From Opportunity to Health

Integrating Videoconferencing Into Treatment for Obsessive-Compulsive Disorder: Practical Strategies With Case Examples

Addiction Medicine Practice-Based Research Network (AMNet): Building Partnerships

Defining and Addressing Gaps in Care for Obsessive-Compulsive Disorder in the United States

"In addition to addressing the emerging role of pharmacists in psychiatric care, July's issue of Psychiatric Services presents research on opportunities and gaps in the treatment of OCD and evidence that stigma responds to brief video interventions," said Psychiatric Services Editor Lisa B. Dixon, M.D., M.P.H. "Part of our mission is to provide evidence-based practices to transform mental health service delivery, and these studies are very much in line with that goal."

BIRMINGHAM, Ala. - An experimental drug reported in Nature Communications suggests that a "path is clearly achievable" to treat currently untreatable cases of cystic fibrosis disease caused by nonsense mutations. This includes about 11 percent of cystic fibrosis patients, as well as patients with other genetic diseases, including Duchenne muscular dystrophy, β-thalassemia and numerous types of cancers, that are also caused by nonsense mutations.

The drug is a small molecule with a novel mechanism of action, say David Bedwell, Ph.D., and Steven Rowe, M.D., MSPH, co-senior authors. Bedwell is professor and chair of the University of Alabama at Birmingham Department of Biochemistry and Molecular Genetics, and Rowe is a professor in the UAB Department of Medicine.

To understand how a nonsense mutation causes disease -- and how the experimental drug works to suppress the mutation -- requires a close look at the biological machinery that makes proteins inside a cell.

A protein is a chain of hundreds of amino acids that then folds to its proper shape and moves to its proper place to perform its function. The chain is made, link by link, by ribosomes that read a sequence for the protein carried on messenger RNA. That sequence instructs which of the 20 different amino acids to add at each link, one by one.

In the disease cystic fibrosis, mutations affect the protein CFTR that functions at the surface of lung cells to regulate the flow of water to the mucus. A malfunctioning or absent CFTR creates very sticky mucus that allows infections in the lungs. A gene mutation that changes one of the nucleotide bases on the messenger RNA may cause an incorrect amino acid to be placed in the protein chain, altering its function. The nonsense premature termination codons that Bedwell and Rowe study cause a different problem -- the mutation forces the ribosome to stop protein synthesis in mid-course, yielding an incomplete protein. It also causes nonsense-mediated mRNA decay.

Thus, Bedwell, Rowe and colleagues wanted to find small-molecule compounds that would make the ribosome skip through the nonsense premature stop mutation, permitting the ribosome to continue full synthesis of the protein. They hoped to find readthrough agents that have a novel mechanism and function better than current ones, such as aminoglycoside antibiotics, which have poor efficacy.

The researchers used rat cells that carried a modified gene from a deep-sea shrimp to test hundreds of thousands of compounds. The gene encodes NanoLuc luciferase, but with a modification to place a premature termination codon in mid-gene. A small molecule that causes the ribosome to readthrough the premature stop would produce intact luciferase, making the cells glow with bright luminescence.

This reporter gene allowed a team at Southern Research to test 771,345 compounds, using high-throughput screening. Of the 180 compounds showing readthrough activity, the small molecule SRI-37240 was the most active.

Researchers found that SRI-37240 restored the function of human CFTR genes with premature termination codon mutations, as tested in rat cell cultures. It significantly increased the amount of CFTR protein and slightly increased the amount of CFTR messenger RNA. An aminoglycoside called G418 is known to aid readthrough of the premature codon mutations, and researchers found that SRI-37240 and G418 acted synergistically to restore CFTR function.

They found that SRI-37240 induces a prolonged pause at stop codons of messenger RNA and inhibits termination of protein synthesis at premature termination codons without stimulating readthrough at the normal termination codons found at the end protein-encoding sequence on the messenger RNA.

Medicinal chemists synthesized 40 derivatives of SRI-37240, and one, SRI-41315, was more potent and showed better physiochemical features. In human cell lines with the NanoLuc reporter gene, SRI-41315 showed much greater readthrough efficiency than SRI-37240, and SRI-41315 acted synergistically with G418.

Ribosome complexes include ribosomal proteins and other proteins that function as termination factors, translation factors and nonsense-mediated mRNA decay factors. The researchers looked at the abundance of seven of those proteins and found that SRI-41315 dramatically reduced a single termination factor called eRF1, through a proteasome degradation-dependent pathway. This novel mechanism has not been previously seen for a pharmacological agent.

To predict clinical efficacy for cystic fibrosis, researchers tested primary human bronchial epithelial cells that had endogenous CFTR premature termination codons. Neither SRI-37240 nor SRI-41315 alone increased CFTR function, but SRI-41315 together with G418 showed a significant increase in function.

This is progress, Bedwell and Rowe say, yet hurdles remain. Unfortunately, the two compounds had a deleterious effect on ion conductance mediated by the epithelial sodium channel, which limits development in their current form as a treatment for cystic fibrosis. The already known readthrough effect of aminoglycosides is also limited because these antibiotics do not restore therapeutic levels of CFTR, and they also must be given intravenously and can be toxic.

Bedwell and Rowe say it is increasingly likely that multiple distinct agents with different mechanisms of action will be required to impart a clinically impactful response. They concluded, "While further medicinal chemistry is needed to identify readthrough compounds that maximally impact CFTR function without undesirable off-target effects, the results presented here suggest this path is clearly achievable."

Scientists from the University of Graz, Kanzelhöhe Observatory, Skoltech, and the World Data Center SILSO at the Royal Observatory of Belgium, have presented the Catalogue of Hemispheric Sunspot Numbers. It will enable more accurate predictions of the solar cycle and space weather, which can affect human-made infrastructure both on Earth and in orbit. The study came out in the Astronomy & Astrophysics journal, and the catalogue is available from SILSO -- the World Data Center for the production, preservation, and dissemination of the international sunspot number.

Our Sun is a big boiling ball of gas, most of which is so hot that electrons are ripped off from atoms, creating a circulating mix of charged particles, called plasma. These moving charges endow the Sun with an enormous magnetic field, which bundles up as it rises from the solar interior and creates dark areas known as sunspots on the surface.

Sunspots are the primary sources of solar flares and coronal mass ejections, or CMEs. These are huge magnetic clouds of plasma released from the Sun at great speeds. When directed toward the Earth, they cause powerful magnetic disturbances that can damage the equipment on satellites, incapacitate telecommunications, and even cause blackouts in a city -- with devastating effects on the economy.

The appearance and disappearance of sunspots varies according to a roughly 11-year cycle. It begins with almost no sunspots. As it progresses, more and more spots emerge on the middle latitudes and migrate to the solar equator. Since the Sun's equator rotates faster than the poles, its magnetic field becomes entangled and strengthened in bundles over the course of the cycle. Eventually, the field line bundles become strong enough to get pushed out through the photosphere as loops that trap and eject plasma as CMEs.

Monitoring sunspots is therefore crucial for predicting dangerous space weather events and their effects on air travelers, astronauts, and the equipment and infrastructure -- both on Earth, in orbit, and on long-term space missions.

Initially observed by Galileo in the 17th century, sunspots are now monitored daily by about 80 observatories across the world. The World Data Center SILSO at the Royal Observatory of Belgium is the global hub for all sunspot data. Systematic data on the total count of sunspots is available starting from the 18th century. However, recent models suggest that solar activity is better understood as an interplay between the activities in the northern and the southern hemispheres considered separately. Such data is much more scarce, with the most important solar activity index -- the International Sunspot Number -- only recording sunspot counts by hemisphere since 1992.

The authors of the recent study in Astronomy & Astrophysics came up with a method to greatly extend the available data by reconstructing historical hemispheric sunspot numbers. As a result, they released a continuous catalogue of daily and monthly data of the northern and southern hemispheric sunspot numbers going back to 1874. The team showed its high correspondence to the existing hemispheric data and demonstrated that solar cycle predictions are indeed more accurate when the evolution of sunspot numbers is considered separately for the two hemispheres.

"Our Sun is an intriguing star, and its physics is both simple and complicated. We have learned from our study that we can obtain a better understanding of the long-term evolution of the Sun's activity by simply treating first the two hemispheres separately and only afterwards summing both contributions up to obtain the overall activity. The newly reconstructed data on hemispheric sunspot numbers will be available to the scientific community, and we believe they can provide an important basis to develop new, more accurate prediction schemes of solar activity," said Astrid Veronig, the lead author of the study, professor at the University of Graz, and head of the Kanzelhöhe Observatory for Solar and Environmental Research.

Skoltech graduate student and study co-author Shantanu Jain highlighted the practical utility of the new catalogue: "We believe that this new catalogue will be essential to accurately predict space weather since we now have continuous hemispheric data for a longer period to make meaningful solar cycle predictions. If we were to face extreme solar eruptions in today's age of technological dependency, it could easily knock out our power grids, satellite communications, the internet, and cause economic losses of up to trillions of dollars. An accurate prediction of space weather can help prepare ourselves and avoid such a scenario."

"For permanent technical infrastructures, for long-term issues like ozone depletion or climate, and in view of future long-duration manned space missions to the Moon or Mars, there is a growing need for mid- and long-term forecasts of the trend of solar activity over the next few months or years. As part of an emerging discipline called 'space climate,' such long-term predictions of the strength of the solar cycle can only rest on a detailed knowledge of the actual evolution of many past solar cycles. Our new extended data series is one of the key steps in the growing efforts to revisit and fully exploit legacy data collections using the modern tools of the 21st century," study co-author and the head of the World Data Center SILSO Frédéric Clette commented.

"Currently, we still do not fully understand how the solar dynamo works and how the solar magnetic field is generated during the 11-year solar cycle. All the planets of our solar system orbit around the Sun in a so-called ecliptic plane. It means that observatories on Earth or instruments on board any Earth-orbiting satellite which make images of the Sun never really see what happens on the solar poles. However, in February 2020 a groundbreaking space mission -- the Solar Orbiter -- was launched to fly very close to the Sun. It will perform gravitational maneuvers to reach out of the ecliptic and glimpse at the poles for the first time in history. The first polar pass is expected to take place in March 2025 with the spacecraft reaching an inclination of 17 degrees above the ecliptic plane and increasing to 33 degrees in July 2029. We think that the newly developed product of hemispheric sunspot numbers together with the unprecedented observations and fundamentally new knowledge from the Solar Orbiter will help us to advance solar cycle studies and space weather predictions. And whatever storms may rage, we wish everyone good weather in space," said Tatiana Podladchikova, a co-author of the paper and assistant professor at the Skoltech Space Center.

A new study published in Accident Analysis & Prevention shows how biometric data can be used to find potentially challenging and dangerous areas of urban infrastructure before a crash occurs. Lead author Megan Ryerson led a team of researchers in the Stuart Weitzman School of Design and the School of Engineering and Applied Science in collecting and analyzing eye-tracking data from cyclists navigating Philadelphia's streets. The team found that individual-based metrics can provide a more proactive approach for designing safer roadways for bicyclists and pedestrians.

Current federal rules for installing safe transportation interventions at an unsafe crossing--such as a crosswalk with a traffic signal--require either a minimum of 90-100 pedestrians crossing this location every hour or a minimum of five pedestrians struck by a driver at that location in one year. Ryerson says that the practice of planning safety interventions reactively with a "literal human cost," has motivated her and her team to find more proactive safety metrics that don't require waiting for tragic results.

Part of the challenge, says Ryerson, is that transportation systems are designed and refined using metrics like crash or fatality data instead of data on human behavior to help understand what makes an area unsafe or what specific interventions would be the most impactful. This reactive approach also fails to capture where people might want to cross but don't because they consider it too dangerous and that, if it were safe, more people would utilize.

"Today we have technology, data science, and the capability to study safety in ways that we didn't have when the field of transportation safety was born," says Ryerson. "We don't have to be reactive in planning safe transportation systems; we can instead develop innovative, proactive ways to evaluate the safety of our infrastructure."

The team developed an approach to evaluate cognitive workload, a measure of a person's ability to perceive and process information, in cyclists. Cognitive workload studies are frequently used in other fields of transportation, such as air traffic control and driving simulations, to determine what designs or conditions enable people to process the information around them. But studies looking at cognitive workload in bicyclists and pedestrians are not as common due to a number of factors, including the difficulty of developing realistic cycling simulations.

The researchers in Ryerson's lab looked at how different infrastructure designs elicit changes in cognitive workload and stress in urban cyclists. In 2018, the team had 39 cyclists travel along a U-shaped route from JFK Boulevard and Market Street, down 15th Street to 20th Street, then returning back to 15th and Market. Riders wore Tobii eye-tracking glasses equipped with inward- and outward-facing camera and a gyroscope capable of collecting eye- and head-movement data 100 times per second.

Along with the route being one of Philadelphia's newest protected bicycle lanes at the time, and therefore a new experience for all of the study participants, it also has a dramatic change in infrastructure along the 8-10-minute route, including a mix of protected bike lanes, car-bike mixing zones, and completely unprotected areas. "We felt that, in a short segment of space, our subjects could experience a range of transportation-infrastructure designs which may elicit different stress and cogitative workload responses," Ryerson says.

One of the study's main findings is the ability to correlate locations that have disproportionately high numbers of crashes with a consistent biometric response that indicates increased cognitive workload. If a person's cognitive workload is high, Ryerson says, it doesn't necessarily mean that they will crash, but it does mean that a person is less able to process new information, like a pedestrian or a driver entering the bike lane, and react appropriately. High cognitive workload means the threat of a crash is heightened.

In addition, the researchers found that stressful areas were consistent between expert cyclists and those less experienced or confident. This has implications for current approaches to managing safety, which typically focus on pedestrian- and cyclist-education interventions. Education is still important, Ryerson says, but these results show that infrastructure design is just as important in terms of making spaces safe.

"Even if you're a more competent cyclist than I am, we still have very similar stress and workload profiles as we traverse the city," says Ryerson. "Our finding, that safety and stress are a function of the infrastructure design and not the individual, is a shift in perspective for the transportation-safety community. We can, and must, build safety into our transportation systems."

The Ryerson lab is now analyzing a separate eye-tracking dataset from cyclists traveling Spruce and Pine streets before and after the 2019-20 installation of protected bike lanes, an experiment that will allow closer study of the impacts of a design intervention.

Overall, Ryerson says, the research shows that it's possible to be more proactive about safety and that city planners could use individual-level data to identify areas where a traffic intervention might be useful--before anyone is hit by a car. "The COVID-19 pandemic encouraged so many of us to walk and bike for commuting and recreation. Sadly, it also brought an increase in crashes. We must proactively design safer streets and not wait to count more crashes and deaths. We can use the way people feel as they move through the city as a way to design safer transportation systems," she says.