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State handgun purchaser licensing laws--which go beyond federal background checks by requiring a prospective buyer to apply for a license or permit from state or local law enforcement--appear to be highly effective at reducing firearm homicide and suicide rates, according to a new analysis of gun laws in four states from researchers at the Johns Hopkins Bloomberg School of Public Health.

The study, published online August 20 in the American Journal of Public Health, looked at changes in gun laws in Connecticut, Missouri, Maryland, and Pennsylvania and modeled trends in firearm homicide and suicide rates for up to a 22-year period.

Connecticut's purchaser licensing law, enacted in 1995, was associated with a 28 percent decrease in firearm homicide rates and a 33 percent decrease in firearm suicides from 1996 to 2017. Reductions in firearm suicide rates associated with the law grew over time from 23 percent from 1996 to 2006 to 40.5 percent from 2007 to 2017. During the later period, Connecticut also increased its use of a law allowing police to temporarily remove firearms from individuals threatening to harm themselves or others.

In contrast, Missouri's repeal of its purchaser licensing law in 2007 was associated with a 47 percent increase in the rate of firearm homicides and a 23.5 percent increase in firearm suicide rates from 2007 to 2016.

The researchers also looked at two states that implemented comprehensive background check laws for handguns that did not include purchaser licensing requirements. Maryland's implementation of comprehensive background check laws in 1996 was associated with a 17.5 percent increase in firearm homicide rates from 1997 to 2013. The law was not linked with significant changes in firearm homicide rates outside of Baltimore City. Maryland's background check requirements were associated with a 15 percent decline in firearm suicides; however, nonfirearm suicides also declined.

The study did not examine Maryland's purchaser licensing law, enacted in 2013, as there were too few years of post-implementation data available.

Pennsylvania enacted a comprehensive background check law in 1996 which was associated with a 21.5 percent increase of firearm homicide rates and a non-significant change in firearm suicides. Like Maryland, it did not have a purchaser licensing requirement during the study period.

The findings contribute to a growing body of evidence that purchaser licensing with comprehensive background checks is a highly effective policy for reducing gun-related deaths.

"So much of the gun policy discussion focuses on background checks alone," says lead author Alex McCourt, PhD, JD, assistant scientist with the Center for Gun Policy and Research in the Department of Health Policy and Management at the Bloomberg School. "We need to recognize that background checks are necessary for identifying people prohibited from accessing a firearm, but, unless complemented by licensing, our research indicates they are not sufficient to reduce gun fatalities."

Federal law requires that a prospective buyer undergo a background check if they purchase a firearm, but only if they purchase it from a licensed dealer. Twenty-two states have extended this requirement to apply to private firearm transfers. Nine of these states, including Connecticut, Hawaii, Iowa, Illinois, Maryland, Massachusetts, New Jersey, New York, and North Carolina, and the District of Columbia have passed laws that require prospective buyers to first obtain a license or permit-to-purchase, at least for handguns.

Each state is different, but states with such licensing laws typically require gun buyers to apply for a license with a state or local law enforcement agency, pass a background check, submit fingerprints, and, in some cases, show evidence of gun safety training. Use of an applicant's fingerprints allows law enforcement to more accurately identify an individual's prior convictions or other prohibiting conditions that might otherwise be missed. States with licensing laws typically have more thorough processes for checking backgrounds, allow law enforcement more time to conduct those checks, and/or have mandatory waiting periods.

For the study, the researchers compared firearm homicide, nonfirearm homicide, firearm suicide, and nonfirearm suicide rates in the four states to synthetic control states--modeled states created to reflect what would have happened if a state did not adopt comprehensive background checks and/or purchaser licensing laws during the same time period.

The study periods for each state were determined by the amount of data available following the law change and the state's policy landscape. The researchers looked at Pennsylvania data from 1985-2017, Maryland data from 1985-2013, Missouri data from 1997-2016, and Connecticut data from 1985-2017.

Using the Centers for Disease Control and Prevention's annual mortality data from 1985-2017, the researchers calculated the percent change in homicides and suicides, both with and without involvement of a firearm, between the state with the policy of interest and its synthetic control.

For purchaser licensing laws, the researchers found that rates of homicides and suicides that did not involve firearms did not change significantly in Connecticut relative to its synthetic control. In Missouri, there was an 18 percent increase in nonfirearm homicide rates associated with the repeal of the state's handgun purchaser licensing law and no significant change in nonfirearm suicide rates. The significant increase in nonfirearm homicide in Missouri suggests that factors other than the law's repeal may have contributed to rising homicide rates from 2008-2016.

The researchers found that following the implementation of comprehensive background check laws, Maryland saw a 33 percent increase in nonfirearm homicide rates and a 22 percent decrease in nonfirearm suicides relative to the control states. In Pennsylvania, nonfirearm homicide rates were 10 percent lower than the synthetic control and the state saw a 12 percent decrease in nonfirearm suicides.

The study also examined if homicide increases in Maryland and Pennsylvania might be partially explained by factors unique to large cities. When Baltimore was excluded from the Maryland analysis, comprehensive background check laws were not associated with significant changes in either firearm or nonfirearm homicides, suggesting that increases in state homicide rates may have been specific to Baltimore. Unlike Maryland, however, firearm homicide and nonfirearm homicide rates increased when Philadelphia data was excluded from the Pennsylvania models.

The researchers suggest that, in addition to adding licensing requirements, comprehensive background check laws can be more effective by more robustly enforcing the laws to promote compliance, broadening prohibiting conditions, improving recordkeeping, and expanding the time to complete the background checks.

"Purchaser licensing has an extremely strong evidence base and research has consistently found protective effects on a range of issues," says co-author Cassandra Crifasi, PhD, MPH, deputy director of the Center. "These laws also have broad public support among Americans, including the majority of gun owners. States looking to advance evidence-based policies to reduce gun violence should consider a purchaser licensing law."

Large forces of trained community health workers and standardised healthcare systems could reduce the number of maternal, newborn and foetal deaths, a study has recommended.

Meta-analysis of three studies, published today in the Lancet, examines the outcomes of 70,000 women in Mozambique, Pakistan and India between 2014-7.

The study aimed to reduce deaths associated with pre-eclampsia. Pre-eclampsia is a condition that causes high blood pressure during pregnancy and after labour. Globally, pre-eclampsia is the second leading cause of maternal mortality, with 76,000 maternal deaths and 500,000 foetal and new-born deaths every year worldwide. Delays in triage, transport to healthcare facilities and treatment contribute to the high numbers of deaths among mothers and infants.

The Community Level Interventions for Pre-eclampsia (CLIP) trials divided women between control and intervention groups. Control groups continued with their local standard of care, whereas intervention groups had access to community health workers who could detect, treat, and refer to hospital women with hypertension, a symptom of pre-eclampsia. Women were also taught how to recognise problems during pregnancy and health workers had access to an app that could help determine the risk to patients and blood pressure and blood oxygen devices so that they could assess women in their homes.

The analysis shows that when there were enough community health workers to provide care there were fewer deaths of mothers, fewer stillbirths and fewer deaths of newborns. However, when there were not enough community health workers, there was no impact.

Researchers recommended expanding the community health worker workforce so individual women were in contact with care providers at least eight times in each pregnancy, and to improve standards of healthcare systems.

Professor Peter von Dadelszen, from King's College London, said: "We designed the three CLIP trials in Pakistan, India, and Mozambique to have the results pulled together into this analysis. Previously, most efforts had focussed on hospital-based care and we moved the focus to the care of pregnant women in their communities, with that care being given by community health workers. Overall, a shortage of community health workers in these communities meant that we did not improve outcomes through our intervention. However, when implemented as planned, these digital health-supported community health workers assessing women in their homes were able to prevent the deaths of pregnant women and their babies both before and soon after birth."

While there is broad support in the United States for pro-vaccination policies, as many as 20% of Americans hold negative views about vaccination. Such misinformed vaccine beliefs are by far the strongest driver of opposition to pro-vaccination public policies - more than political partisanship, education, religiosity or other sociodemographic factors, according to new research from the Annenberg Public Policy Center (APPC) of the University of Pennsylvania.

The findings, published online in the American Journal of Public Health, show how misperceptions about vaccination have the potential to shape public policy. The study is based on an APPC multi-wave panel survey of 1,938 U.S. adult respondents conducted in 2019, during the United States' largest measles outbreak in a quarter-century.

The researchers found that belief in a group of negative misperceptions about vaccination:

reduced the probability of strongly supporting mandatory childhood vaccines by 70%,

reduced the probability of strongly opposing religious exemptions by 66%, and

reduced the probability of strongly opposing personal belief exemptions by 79%.

"There are real implications here for a vaccine for COVID-19," said lead author and former APPC postdoctoral fellow Dominik Stecula, an assistant professor of political science at Colorado State University. "The negative vaccine beliefs we examined aren't limited only to the measles, mumps and rubella (MMR) vaccine, but are general attitudes about vaccination. There needs to be an education campaign by public health professionals and journalists, among others, to preemptively correct misinformation and prepare the public for acceptance of a COVID-19 vaccine."

Stecula was on a team of APPC researchers that included former APPC postdoctoral fellow Ozan Kuru; Dolores Albarracín of the University of Illinois at Urbana-Champaign, who is an APPC distinguished research fellow; and APPC Director Kathleen Hall Jamieson.

Broad support for vaccination

Overall, the researchers found strong support for pro-vaccination policies in the United States:

72% of U.S. adults strongly or somewhat supported mandatory childhood vaccination,

60% strongly or somewhat opposed religious exemptions for vaccines, and

66% strongly or somewhat opposed personal belief exemptions in their states.

"On the one hand, these are big majorities: Well above 50% of Americans support mandatory childhood vaccinations and oppose religious and personal belief exemptions to vaccination," said Kuru, an assistant professor of communications and new media at the National University of Singapore. "Still, we need a stronger consensus in the public to bolster pro-vaccine attitudes and legislation and thus achieve community immunity."

With the current COVID-19 pandemic, the portion of the population that needs to be exposed to the disease or inoculated to achieve community immunity is not yet known.

Research on vaccine beliefs

The researchers drew from a probability-based, nationally representative sample of U.S. adults, specifically from two waves conducted in February-March and September-October 2019. They measured negative beliefs in vaccination by asking respondents about four common claims by those who view vaccination skeptically, including the beliefs that: vaccines cause autism; vaccines are full of toxins; delaying vaccination and altering the vaccine schedule is not harmful; and developing natural immunity by catching the disease is superior to getting vaccinated.

The analysis controlled for a variety of theoretically relevant variables that could shape views about vaccination, including gender, education, income, and age, as well as self-described religiosity, partisanship, the presence of children in the household, and recent exposure to news about measles and the MMR in traditional (print and broadcast) and social media.

An earlier study from the Annenberg Public Policy Center, also using survey data collected during the 2018-19 measles outbreak, found that people who rely on social media were more likely to be misinformed about vaccines. Another APPC study found that people who used conservative or social media at the outset of the COVID-19 pandemic were more likely to be misinformed about how to prevent the virus and believe conspiracy theories about it.

Philadelphia, August 20, 2020 - In a new study, investigators found that ideal cardiovascular health, which is indicative of a healthy lifestyle, was associated with lower odds for ocular diseases especially diabetic retinopathy. These findings appearing in the American Journal of Medicine, published by Elsevier, suggest that interventions to prevent cardiovascular diseases may also hold promise in preventing ocular diseases.

Globally, about 2.2 billion people suffer from ocular diseases leading to vision impairment or blindness. Approximately half of these cases could have been prevented. The leading causes of vision impairment or blindness are age-related macular degeneration, diabetic retinopathy, cataract, and glaucoma.

"Earlier studies have observed associations between eye diseases and individual lifestyle factors such as smoking, obesity, or hypertension," explained lead investigator Duke Appiah, PhD, MPH, Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX, USA. "It is known that these metrics of ideal cardiovascular health do not work alone and may interact additively to result in diseases. However, prior to our research, no other studies have comprehensively evaluated the association of all of the metrics of ideal cardiovascular health with ocular diseases."

Most ocular diseases show few symptoms at early stages and many people may not seek medical care despite readily available treatments. A recent online nationwide survey consisting of all racial and ethnic groups in the United States conducted by the Wilmer Eye Institute at Johns Hopkins University School of Medicine showed that 88 percent of the 2,044 respondents considered good vision to be vital to overall health with 47 percent of them rating losing their vision as the worst disease that could ever happen to them. Alarmingly, 25 percent did not have any knowledge about ocular diseases and their risk factors.

This research shows that following healthy lifestyle and behavior habits can all contribute to good cardiovascular health as assessed by adherence to the American Heart Association's prescription for health metric known as Life's Simple Seven (LS7). LS7 is based on the status of seven cardiovascular disease risk factors: not smoking, regular physical activity, healthy diet, maintaining normal weight, and controlling cholesterol, blood pressure, and blood glucose levels.

Practicing these healthy lifestyles together was found to be associated with lower odds for age-related macular degeneration, diabetic retinopathy, cataract, and glaucoma. Individuals with optimal cardiovascular health had 97 percent lower odds for diabetic retinopathy compared to individuals with inadequate cardiovascular health.

Investigators evaluated data from 6,118 adults aged 40 or more years old who took part in the 2005-2008 National Health and Nutrition Examination Survey. The average age of participants was 57 years old, 53 percent of whom were women. A one unit increase in LS7 scores was associated with reduced odds for age-related macular degeneration, diabetic retinopathy, and glaucoma.

"Overall, we believe that primary prevention and early detection approaches of ocular diseases are important, considering that over half of all deaths from ocular diseases and cardiovascular diseases are known to be preventable," commented co-investigators Noah De La Cruz, MPH, and Obadeh Shabaneh, MPH, both from the Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX, USA.

Since there is a significant overlap of the risk factors for ocular diseases and cardiovascular disease, the investigators recommended that screening for ocular diseases be incorporated into existing clinical and population-based screenings for cardiovascular diseases.

"We hope that our study findings will encourage adherence to healthy lifestyles in order to prevent these age-related diseases while also leading to increased collaborations between cardiologists, optometrists, and ophthalmologists in order to better prevent cardiovascular and ocular diseases," noted Dr. Appiah.

TUSCALOOSA, Ala. - The prevalence of morbid obesity in a population is associated with negative outcomes from COVID-19, according to an analysis by researchers at The University of Alabama of morbid obesity data and reported COVID-19 deaths in the United States.

In a paper published in the journal World Medical and Health Policy, researchers found a statistically significant relationship between the prevalence of morbid obesity and cases of -- and deaths from -- COVID-19, the disease caused by the novel coronavirus. The researchers suggest their findings can help identify resources needed for morbidly obese patients and inform mitigation policies.

"Health practitioners and policymakers need to understand the influence that morbid obesity has on negative COVID?19 outcomes in order to respond to this and similar emerging infectious diseases in the future," said Dr. Kevin Curtin, UA professor of geography.

Obesity is known to increase risk from respiratory infections and hinder pulmonary function, and there's an emerging pattern in the treatment of COVID-19 patients that obesity is a pervasive problem and associated with negative health outcomes such as requiring a ventilator.

"The current global pandemic of COVID?19, which is highly contagious with presumed high mortality rates, has dramatically increased the need to understand the association between obesity and negative health outcomes from respiratory disease, particularly death," said Dr. Lisa Pawloski, professor of anthropology and associate dean for international programs for the UA College of Arts & Sciences.

The researchers used deaths from COVID-19 compiled nationally at the county level by The New York Times and estimates of morbid obesity rates for each U.S. county derived from the National Health and Nutrition Examination Survey and population data from the U.S. Census Bureau. The research looked at adults aged 18 to 64 and found that morbid obesity rates are positively correlated with COVID-19 case and death rates, and that morbid obesity rates can explain 9 percent of the variation in COVID-19 death rates.

"As a matter of practical importance, with the complex interactions that are likely to produce negative COVID?19 outcomes, any single variable that can explain more than 9 percent of the variation is worth examining further," Curtin said.

Moreover, by overlaying the data geographically the researchers found that spatial clusters of high rates of morbid obesity are associated with spatial clusters of high rates of COVID-19 deaths.

Although there are anecdotal reports of obesity complications in patients with COVID-19, most formal studies so far of this relationship have been in China, which has lower obesity rates, and in hospital settings. This work, the researchers say, is the first repeatable quantitative analysis that addresses this relationship.

The short term implications of the research could affect treatment and policy. Long term, the findings point to the need to strengthen public health efforts that address obesity.

"The findings suggest that areas with larger obese populations will need greater resources for effective treatment of COVID?19, as more cases and deaths should be expected as compared with the general population," Pawloski said.

CHICAGO--- Deaths due to heart failure and hypertensive heart disease are increasing in the U.S. --particularly in Black women and men -- despite medical and surgical advances in heart disease management, reports a new Northwestern Medicine study.

The study for the first time comprehensively characterizes mortality between 1999-2018 across a spectrum of heart disease types and examines differences between sex and racial groups across age groups and geography. Although ischemic heart disease (coronary artery disease) remains the leading cause of heart disease deaths, the study reports heart failure and hypertensive heart disease is growing rapidly.

"These findings are alarming," said senior study author Dr. Sadiya Khan, assistant professor of preventive medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. "Despite medical and surgical advances in heart disease management and public policy initiatives around blood pressure awareness, we are losing ground in the battle against heart failure and hypertension. And the disparities in heart disease are clear."

Between 2011-2018, the death rate due to heart disease declined by 0.7% per year. Over this same time period, the death rate due specifically to ischemic heart disease (coronary artery disease) declined by 2.6% per year. But these gains were offset by significant increases in deaths due to heart failure (3.5% per year) and hypertensive heart disease (4.8%/year).

In total, deaths from heart disease in 2018 accounted for 3.8 million potential years of life lost with 30% and 60% greater years of life lost for Blacks compared with white men and women, respectively.

The study will be published Thursday in the British Medical Journal.

The disparities observed in heart failure and hypertensive heart diseases are likely due to higher rates of high blood pressure, obesity and diabetes in Black women and men, Khan said.

"But, we have to recognize and address that the root causes of these disparities arise from differences in social determinants of health, such as socioeconomic status and access to care, and structural and systemic racism in our country," Khan said.

Knowing the types of heart disease that are increasing, and in which groups, can help inform how to equitably target prevention earlier in life, especially for heart failure and hypertension, noted study first author Dr. Nilay Shah, instructor of cardiology and preventive medicine at Feinberg and a Northwestern Medicine physician.

"These findings should be a wake-up call that without equitable access to care and community-engaged implementation of evidence-based therapies for the people who need them, we will not be able to reverse these unfavorable trends," Khan said.

The study used standard data collected from death certificates across the country to identify trends across time in deaths from leading causes of heart disease deaths (ischemic heart disease, heart failure, heart disease related to high blood pressure, valvular heart disease, arrhythmias, heart disease related to lung disease, and other heart diseases), in Black and white women and men, across age groups and in urban and rural areas. The data source was the Centers for Disease Control and Prevention's WONDER database.

"These findings emphasize the urgency with which we need to change how we are approaching cardiovascular health, which continues to be reactive and shift towards a proactive/preventive approach," Khan said. "We need to set up the systems and resources to help our patients preserve and protect their heart health. We needed this before the COVID-19 pandemic and the need is even more urgent with disparities in the context of the current pandemic. People with high blood pressure or obesity have more severe outcomes related to COVID-19. This might portend even greater increases in heart disease deaths in the long-term among people who recover from it."

Life can change dramatically when someone learns they are genetically predisposed to a disease, such as a condition called familial hypercholesterolemia, where a mutated gene can lead to elevated cholesterol and increased risk for a premature heart attack. But these kinds of disease predictions are complicated: not everyone carrying such high-risk single-gene variants develops the disease.

Now, researchers at the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), and Harvard Medical School, in partnership with IBM Research and health technology company Color, have discovered a possible reason why. They studied genetic and clinical data from more than 80,000 people and found that a person's genetic background influences not only the risk of heart disease in people carrying familial hypercholesterolemia gene variants, but also the risks of breast cancer and colorectal cancer in individuals with high-risk single-gene variants that predispose them to these diseases.

Moreover, the team discovered that for some people with these high-risk single-gene variants, having a low polygenic score--which accounts for the small contributions from many common genetic variants for disease spread throughout the genome--could lower their risk of disease, bringing it closer to the population average.

These findings, published in Nature Communications, have both biological and clinical implications. They help explain why some genetically predisposed individuals do not develop disease, and also suggest ways to more accurately interpret patients' genetic risk of disease. Eventually, insight from this study could guide more informed decision-making and genetic counseling in clinical practice -- for example, to more accurately identify patients who should undergo more frequent disease screenings.

"Patients and clinicians often assume that having a high-risk variant makes eventually getting the disease all but inevitable, but an important subset actually go on to live their lives normally," said Akl Fahed, co-first author of the study, who is a cardiology fellow at MGH, and a postdoctoral fellow in Broad's Program in Medical and Population Genetics (MPG). "The traditional approach is to focus on a single base pair mutation linked to disease, but there are 3 billion base pairs in the genome. So we asked whether the rest of your genome can help explain the differing rates of disease we see in these patients, and the answer was a clear yes."

Minxian Wang of the Broad and Julian Homburger of Color were the other first co-authors of the study.

Polygenic power

The study focused on three diseases: familial hypercholesterolemia, where single-gene variants prevent the body from clearing cholesterol from the bloodstream, elevating heart disease risk; Lynch syndrome, where a fault in DNA-repair genes often leads to colorectal cancer; and hereditary breast cancer, caused by defects in the BRCA1 or BRCA2 genes. Most individuals and families with these high-risk variants remain unaware of their inborn risk, and they can not be reliably identified through family history or other risk factors (detailed in a companion publication).

The researchers analyzed genetic and clinical information from 80,298 individuals -- including 61,664 UK Biobank participants and 19,264 women tested for breast cancer high-risk variants by Color. They looked for people with a particular high-risk variant, calculated their polygenic score for the disease, and then ascertained if the individual developed disease or not through their medical records.

"In trying to do these kinds of studies in the past, there were two main barriers," said senior author Amit V. Khera, a physician-scientist leading a research group in the Center for Genomic Medicine at MGH and associate director of the Broad MPG. "You needed very large datasets of participants with and without high-risk variants, and you needed high-quality polygenic scores calculated in these people to quantify their genetic background. The genetics community is only now beginning to have access to these key tools."

The team found that for a small subset of people with a high-risk single-gene, or 'monogenic,' variant for disease, a high polygenic score more than doubled their overall disease risk, from an estimated average of 35 to 41 percent up to 80 percent.

For example, the researchers estimated an individual's risk of developing heart disease by the age of 75 and analyzed the impact of their monogenic variants and polygenic background, and computed risks as low as 17 percent in those with a high-risk variant but low polygenic scores. But those with a high-risk variant and high polygenic score had a disease risk as high as 78 percent.

This risk gradient for those with high-risk variants ranged from 13 to 76 percent in breast cancer and 11 to 80 percent in colorectal cancer. But in all three diseases, a favorable polygenic background lowered disease risk, bringing it closer to that of an average person without the high-risk variant.

"The changes in risk are striking," Khera noted. "For breast cancer, whether a woman's risk is 13 percent or 76 percent may be very important in terms of whether she chooses to get a mastectomy or undergo frequent screening via imaging. Also, for Lynch syndrome, a more precise risk estimate could similarly be a deciding factor for removing the colon entirely or frequent screening colonoscopies."

These findings are consistent with previous studies, including one that focused on a large cohort of individuals with high-risk variants for breast cancer, and another that analyzed complex traits, such as height or cholesterol levels, in patients in a health care system. More recently, a separate report from Broad researchers also extended this interplay between polygenic and monogenic risk to blood traits and diseases -- indicating that the concept is applicable across human conditions.

Tools for genome interpretation

This study also provides the scientific foundation for a new approach for assessing disease risk, where accounting for genetic background increases accuracy of risk estimation, even for those with a high-risk variant. Beyond genetic factors, the researchers plan to build models accounting for additional non-genetic factors that are also associated with disease risk.

"We studied the interplay of monogenic and polygenic disease risk," Fahed said. "But genetics is only part of the story. For heart disease, risk involves other factors like blood pressure and lifestyle risks such as smoking. It is important to account for these as well and develop more fully integrated risk models."

As polygenic scores and disease risk models make their way into routine medical practice, the researchers say these powerful clinical tools can empower patients to better understand, predict, and prevent disease using genetic information -- an idea that Khera is already implementing in MGH's Preventive Genomics Clinic, which he co-founded. This fall, the clinic will begin offering a clinical test developed by Color that assesses both monogenic and polygenic risk for heart disease.

"We are thrilled to be able to offer state-of-the-art genetic risk assessment to our patients in the coming months. One of our next steps is to educate doctors and patients on more advanced types of genetic risk predictors, such as polygenic scores," Khera said. "But there's also important work to be done to further validate integrated genetic risk models in additional populations. The ability to reliably classify monogenic variants as high-risk and stratify the population using polygenic scores is higher in people of European ancestry than other groups, just because that is where most of our training data comes from. So, we need to diversify datasets and improve the models so that they work well for people from different ancestries, ensuring that genomic risk stratification benefits everyone."

A research group led by Professor MORI Yasuko (of the Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine) has revealed that the HHV-6B glycoprotein complex gH/gL/gQ1/gQ2 is an effective vaccine candidate for human herpesvirus 6B (HHV-6B). There are still no methods to treat nor prevent HHV-6B infection, and this study represents the first attempt in the world at developing a vaccine.

This study was conducted through joint research between the following:

Professor MATOZAKI Takashi et al. of the Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine.

Professor ITO Tomoo et al. of the Department of Diagnostic Pathology at Kobe University Hospital.

Professor NISHIGORI Chikako of the Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine.

Associate Professor AOISHI Taiki of the Vaccine Dynamics Project at BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases of Osaka University.

Professor SUZUKI Ryo of the Laboratory of Drug and Gene Delivery Research, Teikyo University.

The Research Foundation for Microbial Diseases of Osaka University (BIKEN Foundation).

The results were published online in the American scientific journal 'PLOS Pathogens' on July 23.

Main Points

Human herpesvirus 6B (HHV-6B) is a pathogen that infects the vast majority of people when they are infants. It not only causes exanthem subitum (*1), with symptoms of a fever followed by a skin rash (roseola) but can also trigger severe complications with lasting after-effects such as febrile convulsions, encephalitis (brain inflammation) and encephalopathy.

Methods to effectively prevent or treat HHV-6B infection have yet to be established. The infection rate is extremely high and great risks are posed by HHV-6B. It is hoped that the realization of a vaccine would enable infants to be inoculated against HHV-6B, resulting in widespread prevention of this virus.

This research group previously discovered a HHV-6B glycoprotein complex that is an essential factor in HHV-6B infection. In this study, they utilized this complex as a vaccine antigen and analyzed its effectiveness.

The research group inoculated mice with the purified virus antigen combined with immunostimulants known as adjuvants (*2), demonstrating that this induced effective immunity against HHV-6B. Furthermore, the combination with the adjuvants was also shown to induce cellular immunity (*3).

These successful results are a big step towards the realization of a safe and effective vaccine for HHV-6B. It is hoped that this research can proceed to clinical trials.

Research Background

Human herpesvirus 6B (HHV-6B) is passed on to infants via the saliva of family members etc., causing exanthem subitum which has symptoms of a fever over 38°C followed by a rash all over the body (roseola). The overwhelming majority of people are infected with HHV-6B. The infection period is between 6 months and 2 years of age; this coincides with the diminishment of antibodies received from the mother.

In most cases, infants recover without experiencing any serious symptoms, however severe complications can occur. For example, it has been reported that in Japan, around 150 infants a year suffer encephalitis or encephalopathy, resulting in lasting aftereffects in around half of this number. Therefore, it is essential to develop a vaccine to protect infants from HHV-6B infection, as there is currently no established treatment nor preventative measures against the virus.

Previously, Professor Mori's research group discovered the glycoprotein complex gH/gL/gQ1/gQ2, which is expressed on the HHV-6B virus's surface. They also revealed that the interaction between this complex and CD314 (OX40), which is expressed on stimulated T-cells, is the key to infection (Figure 1). An antibody that targets the gH/gL/gQ1/gQ2 complex would be able to prevent HHV-6B infection. Therefore, the group is also conducting research into generating antibodies that can be used on humans from mice antibodies.

From this accumulated knowledge and experience came the following idea: an efficient immune response against HHV-6B infection could be achieved if inoculation with the gH/gl/gQ1/gQ2 complex induced immunity against the complex.

Research Findings

The researchers developed a vaccine based on the HHV-6B gH/gL/gQ1/gQ2 complex. (A Patent Application for the vaccine has been filed by the BIKEN Foundation and Kobe University (Patent Application No. 2017-509816)). They generated the gH/gL/gQ1/gQ2 complex via genetic modification techniques. This complex was utilized as the vaccine antigen and mice were inoculated with this in combination with an adjuvant, and immunity induction was analyzed (Figure 2).

The HHV-6B gH/gL/gQ1/gQ2 complex is a complicated molecule constructed in a cell with four types of protein. A method was developed to grow this complex in a cultivated cell in which all the proteins are expressed at the same time. It was confirmed that the HHV-6B gH/gL/gQ1/gQ2 complexes generated using this method still retained their function of binding to their target receptor molecule, CD134 (OX40).

The complex was combined with the adjuvant aluminum hydroxide (abbreviated to Alum), which is widely used in current vaccines, and administered to mice in several doses. The immune response was analyzed; the results confirmed there were vaccine induced antibodies against the gH/gL/gQ1/gQ2 complex in the serum of the mice, and their serum had actually prevented HHV-6B from infecting the cells. Furthermore, it was shown that the glycoprotein complex itself had activated dendritic cells, inducing innate immunity (*4).

Furthermore, a vaccine with a combination of oligonucleotide D35 (which can induce cellular immunity) and its transporter, the DOTAP lipid, as adjuvants in addition to Alum was developed. This vaccine was demonstrated to induce an even stronger antibody response. Spleen cells were extracted from mice after the immunity experiments and the immune cell responses to the gH/gL/gQ1/gQ2 complex were investigated. The results showed a stronger response to the antigen in the group inoculated with the Alum/D35/DOTAP combination and confirmed that cellular immunity was induced. Additional analysis results revealed that CD4 T-cells were the main responders to the antigen.

The researchers also investigated whether or not the induction of serum antibodies via inoculation with the gH/gL/gQ1/gQ2 complex actually prevented HHV-6B infection in animals (Figure 3). This experiment utilized immune cell-humanized mice (*5) to develop an animal model of HHV-6B infection. As a negative control, humanized mice were administered with serum from mice that had been given a vaccine containing only the adjuvant. The humanized mice were then injected with HHV-6B. The virus proliferated internally and many virus antigens were detected in the spleens of the negative control group.

On the other hand, the virus did not proliferate in humanized mice that received prior administration of serum from mice who were inoculated with the vaccine containing the gH/gL/gQ1/gQ2 complex. Also, there were hardly any virus antigens in the spleens of these humanized mice. This demonstrates that the induced immunity from the vaccine is efficient against HHV-6B infection in mice.

Further Developments

Effective treatment and preventative methods for HHV-6B infection have yet to be established despite the latent risks that it poses to the health of all infants. The results of this research represent a huge step towards the efficient prevention of HHV-6B infection with a vaccine. It was demonstrated that this vaccine, which used the gH/gL/gQ1/gQ2 complex as an antigen, efficiently induced an immune system response. Also, the vaccine is promising from a safety aspect as it is a subunit vaccine (*6) that does not contain other virus-derived molecules, aside from the complex. Currently, many infants are given a combined inoculation against four diseases called the DPT-IPV vaccine (D: Diphtheria, P: pertussis, T: tetanus and IPV: inactivated polio virus) at 3 months of age. It is hoped that HHV-6B inoculation could be added to this vaccine to prevent infants from contracting it.

After infection, HHV-6B remains latent inside its host for their entire life. It can be reactivated by conditions such as drug-induced hypersensitivity syndrome or a decline in immunity, and has been reported to trigger various illnesses. In particular, this as a problem when hematopoietic stem cell transplants are used to treat leukemia, leading to a high frequency of HHV-6B reactivation which can cause life-threatening encephalitis. The vaccine developed by this study, when combined with adjuvants, not only grants humoral immunity (*7) but can also induce cellular immunity. In other words, this vaccine can induce a strong immune response to HHV-6B. It is believed that it could also be used to suppress the HHV-6B infection in those undergoing hematopoietic stem cell transplants.

Next, the researchers will build upon these results, collect data on the effectiveness and safety of the vaccine and then proceed to clinical trials. They aim to bring a pioneering HHV-6B vaccine developed in Japan to the world.

Generic public health messages, such as 'eat 5 fruit and vegetables a day', are more effective at shifting dietary habits than very specific advice and guidance tailored according to individual needs, say researchers.

In the new study from health economists, published in the journal European Economic Review, researchers tested the impact of different public health information on dietary choices across a sample of 300 people from low income backgrounds.

In their experiment, which allocated a budget to individuals and asked them to select items in a shopping basket, participants either received very specific information individualised to them, received generic health information, or received no information at all.

For those provided tailored information, they were given easy-to-understand information about their risks of developing diabetes or heart disease, as well as easy-to-follow dietary and health recommendations to minimise risks.

The team from the universities of Bath and Edinburgh, with international colleagues at the University of Malta, found that participants who received generic health information selected food baskets that, on average, contained less total fat and less saturated fat (approximately 20% less) relative to the no information group, and spent 34% less on unhealthy items. For those receiving tailored information, they found no difference in the number of unhealthy items chosen, nor in the nutritional content of the basket compared to the no information group.

The authors say this is because the majority of those who received tailored information actually got better news about their own health than they might have otherwise imagined. This meant individualised information did not have an effect in the sense that participants were given a 'free pass' to continue with their current (unhealthy) dietary choices.

In the context of efforts to tackle obesity, including through the UK's government's latest obesity strategy in response to COVID-19, the researchers say this work should act as a warning about increasing trends towards individualising health information. They suggest their results may explain why efforts to offer personalised health information by public health agencies have had limited success so far, including the NHS's Health Check programme.

Dr Jonathan James from the Department of Economics at the University of Bath explains: "Over recent years and in an effort to nudge us towards healthier behaviours there has been increased reliance on tailoring health information to make it very specific to individuals. This is premised on a theory that by individualising advice and guidance it will have more resonance with individuals and be harder to ignore.

"Yet, as our study shows, tailoring health information in this way is not a silver bullet in tackling obesity; it can actually be less effective at shifting behaviours than generic health information which is relevant to all. As we observed, this can be because the tailored information provided actually gives a better assessment of someone's health than they may have imagined and therefore inadvertently gives them a free pass to continue to eat unhealthily."

Co-author Dr Jonathan Spiteri from the University of Malta added: "Policymakers designing responses to obesity need to bear these results in mind when considering future health interventions. Often keeping it general when it comes to public health messages will also make it most effective."

These findings on the impact of generic information are in line with recent evidence on the effectiveness of information made available at the time of purchase, such as calorie and health information on product labels.

Philadelphia, August 20, 2020 - Philadelphia and its surrounding counties issued a series of "stay-at-home" orders on March 17, 2020 in an effort to curb the spread of COVID-19. In the months that followed, Children's Hospital of Philadelphia (CHOP) saw a marked decrease in healthcare visits for both outpatient and hospitalized asthma patients. New research from CHOP and the Hospital of the University of Pennsylvania suggests the cause may have been fewer rhinovirus infections due to masking, social distancing, and hygiene measures.

The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

Researchers reviewed the 60 days leading up to March 17, 2020 and compared them to the 60 days following stay-at-home orders. They found a 60% decrease in the total daily asthma healthcare visits across CHOP's hospital and Care Network, which includes more than 50 primary care offices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey.

In reviewing cases of rhinovirus after March 17 and comparing them to the number of cases over the same time period in 2015 to 2019, the researchers found cases decreased following the introduction of public health interventions designed to limit viral transmission of SARS-CoV-2. The researchers also analyzed pollution levels after March 17, 2020 and compared them to the same period in 2015 to 2019, but they did not find statistically significant reductions in pollution levels from the available data.

"Pollution and respiratory viruses, particularly rhinovirus, can worsen asthma symptoms and trigger exacerbations," said David A. Hill, MD, PhD, senior author and attending physician with the Division of Allergy and Immunology at CHOP. "When we saw this decrease we initially thought it must be some combination of these factors. We were surprised to see that pollution did not actually decline substantially when compared with historical trends in the Philadelphia region as a result of stay-at-home orders, so we believe this change is more directly a result of infection prevention measures, including wearing a face mask, washing hands frequently, and social distancing. Above all, this paper demonstrates that social distancing is an effective tool in reducing transmission of any virus, whether it's a coronavirus or an asthma-exacerbating rhinovirus."

The researchers analyzed the visits by asthma patients after March 17, 2020 and found telehealth video visits, which were not previously available, became the most highly utilized way of seeing a doctor by asthma patients, with 61% of asthma-related appointments being telehealth visits. The research team also saw a decrease in outpatient steroid prescriptions after stay-at-home orders went into effect. Despite this decrease, Black patients and patients with Medicaid coverage saw the highest rates of steroid prescriptions, with Black patients seeing a 70% increase and Medicaid patients seeing a 63% increase. Black patients made up a lower proportion of telehealth video visits, a difference the authors noted should be the focus of future studies and quality improvement efforts.

"These findings can help inform how we care for asthma patients, not only during this pandemic, but also after we return to a new normal," said Hill. "Asthma is one of the most common chronic childhood diseases, affecting one out of every 12 school-aged children in the United States. We should explore whether enhanced infection-prevention measures have utility in children with asthma, irrespective of COVID-19."

Shifting public health messaging about face coverings from a medical intervention to a social practice could improve uptake

Face coverings need to be grounded in the social and cultural realities of affected communities, say researchers

Encouraging the public to see face masks as a social practice, which they can use to express their cultural background or their personality, could encourage more people to use them regularly, say researchers writing in The BMJ today.

Helene-Mari van der Westhuizen and colleagues at the University of Oxford argue that protracted debates about face coverings as a medical intervention have delayed implementation of a valuable preventive tool - and they say face coverings need to be grounded in the social and cultural realities of affected communities.

Most countries now recommend or mandate the wearing of face coverings to some extent, to reduce the spread of covid-19.

Debate about whether the public should wear them initially focused on the medical narrative of benefits and harms, such as whether they would be effective and whether recommending medical masks would reduce the supply for healthcare professionals.

This view of face masks as a medical intervention has persisted in public health messaging about the use of face coverings. This includes emphasising medial narratives about "donning and doffing," (putting on a face covering in a certain way) "decontamination" (how to clean it ) and "risk" (not touching certain parts of it).

But recognising and embracing the sociocultural narrative of face coverings could encourage the public to select one that is meaningful to them and that they will therefore be more likely to wear, the authors argue.

"Wearing face coverings is being rapidly introduced as a public health intervention in countries with no cultural tradition of doing so," they write. "For successful uptake, such interventions need to be grounded in the social and cultural practices and realities of affected communities, and campaigns should not only inform, but also work to shape new sociocultural norms."

Framed socioculturally, face coverings are clothing or accessories, they explain, and wearing one is a social practice--a behaviour that has a particular meaning in a particular society.

For instance, face coverings have been associated with assuming a different identity (worn by a superhero), avoiding recognition and persecution (worn by a criminal), to exhibit modesty (expected of women in some cultures), having an infectious disease (worn by a patient), for protection (against pollution, dust, pollen) and for cultural ceremonies (worn for celebration).

The symbolic meaning of a face covering to a particular society will also be influenced by social expectations (eg, what we expect a shop assistant, bus driver, or nurse to be wearing), norms (what is viewed as morally correct and as right and proper behaviour), and laws and regulations (whether it is mandatory).

There are examples of face coverings adapting to cultural traditions. For example, in India, a loose end of a piece of clothing, from a saree is now more frequently used also to cover the face during the current pandemic.

In some Asian countries, face coverings have been widely used in public in previous respiratory virus epidemics and uptake during covid-19 has been swift and near universal. This might also be linked to cultural meaning systems that emphasise the boundary between a clean and pure inner self and a potentially polluted outside (similar to the removal of shoes on entering the home).

The ability to personalise cloth face coverings also offers an opportunity to improve uptake through desirability as an accessory, they add.

The wide variation in materials and style raises questions about the efficacy and reliability of face coverings, and public health policy must consider the trade-off between efficacy and compliance, they stress. "A face covering that is 100% effective at preventing transmission but only worn by 10% of the population will have less impact than one that is 50% effective but worn by 95% of the population."

Instead of continuing to debate technical specifications and efficacy, sociocultural framings should be explored to encourage their use, conclude the authors. "This can be done by emphasising underlying values such as solidarity and communal safety. Such measures are likely to enhance the uptake of face coverings and help curb the devastating impact of the pandemic."

August 19, 2020 (DALLAS, TEXAS) - For decades, physicians have known that many kinds of cancer cells often spread first to lymph nodes before traveling to distant organs through the bloodstream. New research from Children's Medical Center Research Institute at UT Southwestern (CRI) provides insight into why this occurs, opening up new targets for treatments that could inhibit the spread of cancer.

The study, published today in Nature, found melanoma cells that pass through the lymph nodes pick up a protective coating, allowing them to survive high levels of oxidative stress in the blood and go on to form distant tumors.

Most cancer deaths happen after cancer spreads to other parts of the body through a process known as metastasis. This occurs when cancer cells from the primary tumor spread through blood vessels or migrate through lymphatic vessels before entering the blood.

"Previous research has focused on how cancer cells metastasize through the blood, but very little was known about how these cells compare to cells that metastasize through lymphatics," says Sean Morrison, Ph.D., the director of CRI and a Howard Hughes Medical Institute (HHMI) investigator. "Our data suggest that passing through the lymphatics can promote the survival and spread of melanoma cells by protecting the cells from the oxidative stress they normally experience during metastasis."

The researchers observed how human melanoma cells behaved when injected intravenously or into the lymphatic system of mice. They found that cancer cells injected into lymph nodes had a better chance of surviving and forming tumors than those injected directly into the blood.

Researchers hypothesized this difference could be explained by the high levels of oxidative stress cancer cells experience when they migrate through the blood. Exposure to oxidative stress in the blood is one reason why metastasis is a very inefficient process in which most cancer cells die before they have an opportunity to grow at a distant site.

"After further analysis, we discovered that the oxidative stress in the blood causes the cancer cells to undergo a specific form of cell death called ferroptosis," says Jessalyn Ubellacker, Ph.D., lead author of the study and a postdoctoral researcher in the Morrison lab. "In contrast, cancer cells in lymph experience lower levels of oxidative stress and are protected from ferroptosis."

To better understand why melanoma cells undergo ferroptosis in the blood but not the lymph, researchers looked for metabolic differences between cancer cells in the blood versus the lymph. They discovered cancer cells from the lymph had higher levels of a monounsaturated fatty acid known as oleic acid, which is the main component of olive oil. They also found this monounsaturated fatty acid was incorporated into the membranes of cancer cells in the lymph. This diluted polyunsaturated fatty acids in the membranes of these cells, inhibiting the chemical reactions that lead to ferroptosis and protecting the cells.

This protective coating of oleic acid from the lymph thus allowed the cancer cells to safely enter the blood, travel to other locations, and form metastatic tumors. This explains why cancer cells often form tumors first in lymph nodes before metastasizing to distant sites through the blood: They are able to load up on antioxidants in the lymph that protect the cells when they subsequently enter the blood.

"Now that we understand more about why cancer cells are most likely to metastasize initially through lymph, it raises the possibility of treating patients with drugs that target those protective mechanisms in the lymph to inhibit the early stages of metastasis," says Morrison.

Researchers have investigated the function of a complex mesh of muscle fibers that line the inner surface of the heart. The study, published in the journal Nature, sheds light on questions asked by Leonardo da Vinci 500 years ago, and shows how the shape of these muscles impacts heart performance and heart failure.

In humans, the heart is the first functional organ to develop and starts beating spontaneously only four weeks after conception. Early in development, the heart grows an intricate network of muscle fibers--called trabeculae--that form geometric patterns on the heart's inner surface. These are thought to help oxygenate the developing heart, but their function in adults has remained an unsolved puzzle since the 16th century.

"Our work significantly advanced our understanding of the importance of myocardial trabeculae," explains Hannah Meyer, a Cold Spring Harbor Laboratory Fellow. "Perhaps even more importantly, we also showed the value of a truly multidisciplinary team of researchers. Only the combination of genetics, clinical research, and bioengineering led us to discover the unexpected role of myocardial trabeculae in the function of the adult heart."

To understand the roles and development of trabeculae, an international team of researchers used artificial intelligence to analyse 25,000 magnetic resonance imaging (MRI) scans of the heart, along with associated heart morphology and genetic data. The study reveals how trabeculae work and develop, and how their shape can influence heart disease. UK Biobank has made the study data openly available.

Leonardo da Vinci was the first to sketch trabeculae and their snowflake-like fractal patterns in the 16th century. He speculated that they warm the blood as it flows through the heart, but their true importance has not been recognized until now.

"Our findings answer very old questions in basic human biology. As large-scale genetic analyses and artificial intelligence progress, we're rebooting our understanding of physiology to an unprecedented scale," says Ewan Birney, deputy director general of EMBL.

The research suggests that the rough surface of the heart ventricles allows blood to flow more efficiently during each heartbeat, just like the dimples on a golf ball reduce air resistance and help the ball travel further.

The study also highlights six regions in human DNA that affect how the fractal patterns in these muscle fibers develop. Intriguingly, the researchers found that two of these regions also regulate branching of nerve cells, suggesting a similar mechanism may be at work in the developing brain.

The researchers discovered that the shape of trabeculae affects the performance of the heart, suggesting a potential link to heart disease. To confirm this, they analyzed genetic data from 50,000 patients and found that different fractal patterns in these muscle fibers affected the risk of developing heart failure. Nearly five million Americans suffer from congestive heart failure.

Further research on trabeculae may help scientists better understand how common heart diseases develop and explore new approaches to treatment.

"Leonardo da Vinci sketched these intricate muscles inside the heart 500 years ago, and it's only now that we're beginning to understand how important they are to human health. This work offers an exciting new direction for research into heart failure," says Declan O'Regan, clinical scientist and consultant radiologist at the MRC London Institute of Medical Sciences. This project included collaborators at Cold Spring Harbor Laboratory, EMBL's European Bioinformatics Institute (EMBL-EBI), the MRC London Institute of Medical Sciences, Heidelberg University, and the Politecnico di Milano.

A team including Wei Liu, assistant professor in ASU's School of Molecular Sciences (SMS) and the Biodesign Institute's Center for Applied Structural Discovery, has published a paper today in Molecular Cell that offers promising details for improved therapeutic treatments for cardiac disease.

Cardiac disease is the number one killer of people worldwide and according to the US Centers for Disease Control (CDC) it kills one person every 37 seconds in the United States.

With this in mind, the team (*see below for details) decided to conduct structural and functional studies using cryo electron microscopy (EM) to capture never-before-seen detailed conformational changes involving the β1-adrenergic receptor (β1-AR) in complex with the Gs protein. The β1-adrenergic receptor is a member of the G protein-coupled receptor (GPCR) family. GPCRs are the largest class of membrane proteins in the human genome.

β1-ARs are predominantly expressed in the adult human heart and dominates as a major regulator of cardiac function. The activated receptor triggers Gs-protein coupling and increased cardiac 3?-5?-cyclic adenosine monophosphate (or cAMP for short) levels. These molecular events manifest physiologically as increased heart rate, increased conduction, reduced refractoriness within the atrioventricular node, increased contractility, and increased cardiac output.

Downregulation of β1-ARs has been seen as the cause of most cases of heart failure, one of the leading causes of morbidity worldwide. Beta-blockers, which are inhibitors of β1-ARs, are used to treat high blood pressure and heart failure, to manage abnormal heart rhythms, and to protect against myocardial infarction.

"In this Molecular Cell paper, we employed cryo-electron microscopy and signaling studies to investigate the molecular mechanism by which β1-AR catalyzes the guanine-nucleotide exchange as the result of Gs activation" says Wei Liu.

"We have captured never-before-seen details of the conformational changes during the Gs activation by isoproterenol-bound β1-AR. Activated β1-AR, serving as a guanine-nucleotide exchange factor (GEF) for Gs, deforms the GDP-binding pocket and induces a tilting of the C-terminal α5-helix and the α-helical domain of Gs rotational opening away from its Ras-like domain," explains Lan Zhu, Assistant Research Scientist in SMS and Biodesign Center for Applied Structural Discovery and one of four co-first authors of this paper.

The other first authors include Minfei Su of Cornell University, Yixiao Zhang of The Rockerfeller University and Navid Paknejad of Memorial Sloan Kettering Cancer Center.

"This structure of the adrenergic receptor complex with the effector G-protein reveals molecular details in the protein-protein interaction domains involved in the receptor activation," explains Liu. "This information allows for the design of new precision therapeutics to target cardiac diseases, one of the leading causes of death in the developed world."

In the past few years, single-particle cryogenic electron microscopy (cryo-EM) in particular has triggered a revolution in structural biology and has become a newly dominant discipline. Cryo-EM allows researchers to take a look at biological structures that were simply not accessible just a few years ago and is now exposing structures of unprecedented complexity in great detail.

Indeed, it is this technique utilized by the experts in the School of Molecular Sciences and the John M. Cowley Center for High Resolution Electron Microscopy in the College of Liberal Arts and Sciences at ASU that has enabled the current research.

"Wei Liu's work is typified by outstanding scholarship and a relentless commitment to making critical advances that will benefit science and society at large," said Ian Gould, interim director of the School of Molecular Sciences.

In conclusion, these new results provide structural insights into the activation mechanism of Gs by β1-AR and offer extremely promising details for improved therapeutic treatments for cardiac disease.

The Covid-19 pandemic has brought about rapid innovation in mental health care, and the move to telemedicine is likely here to stay to at least some degree, but new research led by UCL and King's College London cautions that serious barriers still need to be overcome.

In a new survey in the UK and an international review of evidence from 29 countries, mental health care staff report how the pandemic and lockdown have been harmful to some people accessing mental health services.

The two new studies are published in Social Psychiatry and Psychiatric Epidemiology and are led by the UCL- and KCL-led NIHR Mental Health Policy Research Unit (MHPRU). One is a survey of 2,180 mental health professionals in the UK, and the other is a summary of reports from 872 papers and articles across six continents.

The international review identified multiple reports that the pandemic exacerbated symptoms for people with mental health conditions. Many people had increased anxiety due to concerns about getting infected, while others struggled with the loss of routine, or social isolation and loneliness. Numerous studies raised concerns that social adversities and inequalities may continue to worsen.

Director of the MHPRU, Professor Sonia Johnson (UCL Psychiatry and Camden and Islington NHS Foundation Trust), corresponding author of both studies, said: "People working in mental health care settings across the UK and globally have reported rapid innovation at their workplaces, including the rapid adoption of telemedicine, after years of slow progress.

"Most people we surveyed support partial adoption of remote working, but they caution that telemedicine doesn't work for everyone, and there are still major challenges to be addressed for it be truly effective. The voices of the digitally excluded are especially in danger of not being heard."

Internationally, mental health professionals anticipate an increased need for services as the pandemic drags on, which could be coupled with reduced capacity, with particular concerns for inpatient and residential care settings. Many expressed concerns that coping strategies that have helped people through the lockdown may not be sustainable long-term.

The researchers write that while there is not much official data available yet, mental health care staff from numerous countries reported reduced referrals and visits to mental health services in the very early stages of the pandemic. Potential explanations include fears of infection, beliefs that help would not be available, or concerns about being a burden.

The international survey also identified recurring ethical concerns about maintaining professional standards and human rights in a fast-changing environment. Some sources raised concerns that access to physical health care has become inequitable for people with mental health conditions, due to stigma and policies in some countries to keep them in psychiatric units rather than general hospitals. Others have raised concerns that mental health care might have become less ethical due to some new restrictions and regulations.

In the UK survey, the authors note that a key challenge continues to be managing to combine infection control with a good therapeutic environment. Numerous respondents raised concerns about difficulties with infection control including problematic ward and office layouts, a lack of personal protective equipment (PPE) or of facilities for its proper use, and some service users finding it difficult to understand and adhere to social control.

Christian Dalton-Locke (UCL Psychiatry), co-first author of the UK-focused paper, said: "We found that balancing infection control requirements with maintaining therapeutic relationships with patients who may be distressed, suspicious, or struggling to comprehend the situation, remains an important priority, and, as we have seen with reports of Covid-19 deaths among people subject to the Mental Health Act, the price of failure is potentially very high."

MHPRU Co-Director, Professor Alan Simpson (King's College London's Institute of Psychiatry, Psychology & Neuroscience, Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, and South London and Maudsley NHS Foundation Trust), and senior author on both papers, said: "We found that in the UK and in other countries, mental health care providers have demonstrated considerable agility and flexibility in responding to the pandemic, but staff remain concerned for the future.

"Regarding telemedicine, our sources have given a clear warning that substantial technological, social and procedural barriers remain, and that its use should remain selective, complementing rather than replacing face-to-face contact."

Dr Luke Sheridan Rains (UCL Psychiatry), co-first author of the international paper, said: "Mental health care staff in many countries are concerned about a potential delayed wave of increased demand, putting strain on services with limited resources. The potential long duration of the pandemic suggests that avoiding a crisis in mental health care should be a global priority."