U.S. excess deaths rose nearly 23 percent in 2020, study finds

Extended surges in the South and West in the summer and early winter of 2020 resulted in regional increases in excess death rates, both from COVID-19 and from other causes, a 50-state analysis of excess death trends has found. Virginia Commonwealth University researchers’ latest study notes that Black Americans had the highest excess death rates per capita of any racial or ethnic group in 2020.
The research, publishing Friday in the Journal of the American Medical Association, offers new data from the last 10 months of 2020 on how many Americans died during 2020 as a result of the effects of the pandemic — beyond the number of COVID-19 deaths alone — and which states and racial groups were hit hardest.
The rate of excess deaths — or deaths above the number that would be expected based on averages from the previous five years — is usually consistent, fluctuating 1% to 2% from year to year, said Steven Woolf, M.D., the study’s lead author and director emeritus of VCU’s Center on Society and Health. From March 1, 2020, to Jan. 2, 2021, excess deaths rose a staggering 22.9% nationally, fueled by COVID-19 and deaths from other causes, with regions experiencing surges at different times.
“COVID-19 accounted for roughly 72% of the excess deaths we’re calculating, and that’s similar to what our earlier studies showed. There is a sizable gap between the number of publicly reported COVID-19 deaths and the sum total of excess deaths the country has actually experienced,” Woolf said.
For the other 28% of the nation’s 522,368 excess deaths during that period, some may actually have been from COVID-19, even if the virus was not listed on the death certificates due to reporting issues.
But Woolf said disruptions caused by the pandemic were another cause of the 28% of excess deaths not attributed to COVID-19. Examples might include deaths resulting from not seeking or finding adequate care in an emergency such as a heart attack, experiencing fatal complications from a chronic disease such as diabetes, or facing a behavioral health crisis that led to suicide or drug overdose.

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Sharing Message of Hope on CBS Sunday Morning

For Easter Sunday, I shared a message of hope with viewers of CBS Sunday Morning. My message: We are at a “love your neighbor” moment with the COVID-19 pandemic, a time when Americans can get vaccinated to help protect others from severe illness and death. The vaccines are a gift to all of us. Do your part. Unwrap the gift, roll up your sleeve, and save lives.

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New method expands the world of small RNAs

A team led by a biomedical scientist at the University of California, Riverside, has developed a new RNA-sequencing method — “Panoramic RNA Display by Overcoming RNA Modification Aborted Sequencing,” or PANDORA-seq — that can help discover numerous modified small RNAs that were previously undetectable.
RNA plays a central role in decoding the genetic information in DNA to sustain an organism’s life. It is generally known as the intermediate molecule used to synthesize proteins from DNA. Cells are full of RNA molecules in complex and diverse forms, two main types being ribosomal RNA, or rRNA; and transfer RNA, or tRNA; which are involved in the synthesis of proteins.
Small RNAs play essential roles in health and diseases, including cancer, diabetes, neurological diseases, and infertility. Examples of small RNAs are microRNA; piwi-interacting RNA, or piRNA; and tRNA-derived small RNA, or tsRNA. Small RNAs can get modified by chemical groups and thus acquire new functions.
The development of high-throughput RNA sequencing technologies — useful for examining the quantity and sequences of RNA in a biological sample — has uncovered an expanding repertoire of small RNA populations that fine-tune gene expression and protect genomes.
“PANDORA-seq can be widely used to profile small RNA landscapes in various physiological and disease conditions to facilitate the discovery of key regulatory small RNAs involved in these conditions,” said Qi Chen, an assistant professor of biomedical sciences in the UCR School of Medicine, who led the study published today in Nature Cell Biology. “Modified small RNAs wear an ‘invisibility cloak’ that prevents them from being detected by traditional RNA-sequencing methods. How many such modified RNAs are there? What is the origin of their sequences? And what exactly is their biological function? These are questions PANDORA-seq may be able to answer.”
PANDORA-seq employs a stepwise enzymatic treatment to remove key RNA modifications, which then takes off the invisibility cloak used by the modified small RNAs.

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Masks, ventilation stop COVID spread better than social distancing, study shows

A new study from the University of Central Florida suggests that masks and a good ventilation system are more important than social distancing for reducing the airborne spread of COVID-19 in classrooms.
The research, published recently in the journal Physics of Fluids, comes at a critical time when schools and universities are considering returning to more in-person classes in the fall.
“The research is important as it provides guidance on how we are understanding safety in indoor environments,” says Michael Kinzel, an assistant professor in UCF’s Department of Mechanical and Aerospace Engineering and study co-author.
“The study finds that aerosol transmission routes do not display a need for six feet social distancing when masks are mandated,” he says. “These results highlight that with masks, transmission probability does not decrease with increased physical distancing, which emphasizes how mask mandates may be key to increasing capacity in schools and other places.”
In the study, the researchers created a computer model of a classroom with students and a teacher, then modeled airflow and disease transmission, and calculated airborne-driven transmission risk.
The classroom model was 709 square feet with 9-foot-tall ceilings, similar to a smaller-size, university classroom, Kinzel says. The model had masked students — any one of whom could be infected — and a masked teacher at the front of the classroom.

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Study finds psychiatric disorders persist 15 years after youth are detained

A new study shows that youth arrested as juveniles with psychiatric disorders that remain untreated, struggle with mental health and successful outcomes well beyond adolescence.
Research from Northwestern Medicine shows nearly two-thirds of males and more than one-third of females with one or more existing psychiatric disorders when they entered detention, still had a disorder 15 years later.
The findings are significant because mental health struggles add to the existing racial, ethnic and economic disparities as well as academic challenges from missed school, making a successful transition to adulthood harder to attain.
“Kids get into trouble during adolescence. Those from wealthier families also use drugs and get into fights. But these situations are most often handled informally by the school and parent, and don’t culminate in arrest and detention,” said lead author Linda Teplin, Owen L. Coon Professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.
“These are not necessarily bad kids, but they have many strikes against them. Physical abuse, sexual abuse and neglect are common. These experiences can precipitate depression. Incarceration should be the last resort,” said Teplin, also a faculty associate with the University’s Institute for Policy Research.
The unprecedented longitudinal study reports on the prevalence, persistence and patterns of behavioral and psychiatric disorders in youth up to 15 years after they leave detention and whether outcomes vary by sex and race/ethnicity.

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Mysterious 'nuclear speckle' structures inside cells enhance gene activity, may help block cancers

A team led by scientists at the Perelman School of Medicine at the University of Pennsylvania has illuminated the functions of mysterious structures in cells called “nuclear speckles,” showing that they can work in partnership with a key protein to enhance the activities of specific sets of genes.
The discovery, which will be published on April 5 in Molecular Cell, is an advance in basic cell biology; the key protein it identifies as a working partner of speckles is best known as major tumor-suppressor protein, p53. This avenue of research may also lead to a better future understanding of cancers, and possibly better cancer treatments.
“This study shows that nuclear speckles work as major regulators of gene expression, and suggests that they have a role in some cancers,” said study senior author Shelley Berger, PhD, the Daniel S. Och University Professor in the Department of Cell and Developmental Biology.
Nuclear speckles, tiny structures within the nucleus of every mammalian cell, were first observed with a microscope in 1910, but in the ensuing 111 years, scientists have discovered little about their functions.
One early theory was that the speckles are essentially storage depots, since they do contain important molecules needed to copy out the DNA in genes into RNA transcripts and then to process those transcripts into the finished “messenger RNAs” that can be translated into proteins. In recent years, scientists have begun to find evidence that speckles play a more direct role in gene transcription.
Nevertheless, identifying their precise functions and how those are regulated has been difficult, due to the basic challenges of studying speckles.
In the study, Berger and colleagues, including first author Katherine Alexander, PhD, a postdoctoral researcher in the Berger Laboratory who did most of the experiments, overcame some of these challenges to reveal that speckles work with p53 to directly enhance the activity of certain genes.
While p53 has long been known as a “transcription factor” or master switch that controls the activity of a broad set of genes, the researchers showed that it exerts this effect on a subset of its target genes via nuclear speckles. The protein acts as a matchmaker, bringing together speckles and DNA containing these target genes. When the speckles and genes get close, the level of transcription of the genes jumps significantly.
The researchers went even further to show that the p53 target genes whose activity is boosted via speckles have a set of functions that are broadly distinct from those of other p53 target genes.
“Speckle-associated p53 target genes, compared to other p53 target genes, are more likely to be involved in tumor-suppressing functions such as stopping cell growth and triggering cell suicide,” Alexander said.
These findings not only confirm nuclear speckles as enhancers of gene activity, but also implicate them in the functions of a key tumor-suppressor protein, which is known to be disrupted in about half of all cancers. In some cancers, p53 is mutated in a way that causes it not only to lose its tumor-suppressor function but also to actively drive cancerous growth. The researchers are now working to determine if nuclear speckles are involved in mediating this cancer-driving effect of mutant p53.
“If that proves to be the case,” Berger said, “then in principle we could develop treatments to interfere with this association between p53 and speckles — an association that might turn out to be a real Achilles heel for cancer.”

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Genetic link between face and brain shape

An interdisciplinary team led by KU Leuven and Stanford has identified 76 overlapping genetic locations that shape both our face and our brain. What the researchers didn’t find is evidence that this genetic overlap also predicts someone’s behavioural-cognitive traits or risk of conditions such as Alzheimer’s disease. This means that the findings help to debunk several persistent pseudoscientific claims about what our face reveals about us.
There were already indications of a genetic link between the shape of our face and that of our brain, says Professor Peter Claes from the Laboratory for Imaging Genetics at KU Leuven, who is the joint senior author of the study with Professor Joanna Wysocka from the Stanford University School of Medicine. “But our knowledge on this link was based on model organism research and clinical knowledge of extremely rare conditions,” Claes continues. “We set out to map the genetic link between individuals’ face and brain shape much more broadly, and for commonly occurring genetic variation in the larger, non-clinical population.”
Brain scans and DNA from the UK Biobank
To study genetic underpinnings of brain shape, the team applied a methodology that Peter Claes and his colleagues had already used in the past to identify genes that determine the shape of our face. Claes: “In these previous studies, we analysed 3D images of faces and linked several data points on these faces to genetic information to find correlations.” This way, the researchers were able to identify various genes that shape our face.
For the current study, the team relied on these previously acquired insights as well as the data available in the UK Biobank, a database from which they used the MRI brain scans and genetic information of 20,000 individuals. Claes: “To be able to analyse the MRI scans, we had to measure the brains shown on the scans. Our specific focus was on variations in the folded external surface of the brain — the typical ‘walnut shape’. We then went on to link the data from the image analyses to the available genetic information. This way, we identified 472 genomic locations that have an impact on the shape of our brain. 351 of these locations have never been reported before. To our surprise, we found that as many as 76 genomic locations predictive of the brain shape had previously already been found to be linked to the face shape. This makes the genetic link between face and brain shape a convincing one.”
The team also found evidence that genetic signals that influence both brain and face shape are enriched in the regions of the genome that regulate gene activity during embryogenesis, either in facial progenitor cells or in the developing brain. This makes sense, Wysocka explains, as the development of the brain and the face are coordinated. “But we did not expect that this developmental cross-talk would be so genetically complex and would have such a broad impact on human variation.”
No genetic link with behaviour or neuropsychiatric disorders
At least as important is what the researchers did not find, says Dr Sahin Naqvi from the Stanford University School of Medicine, who is the first author of this study. “We found a clear genetic link between someone’s face and their brain shape, but this overlap is almost completely unrelated to that individual’s behavioural-cognitive traits.”
Concretely: even with advanced technologies, it is impossible to predict someone’s behaviour based on their facial features. Peter Claes continues: “Our results confirm that there is no genetic evidence for a link between someone’s face and that individual’s behaviour. Therefore, we explicitly dissociate ourselves from pseudoscientific claims to the contrary. For instance, some people claim that they can detect aggressive tendencies in faces by means of artificial intelligence. Not only are such projects completely unethical, they also lack a scientific foundation.”
In their study, the authors also briefly address conditions such as Alzheimer’s, schizophrenia, and bipolar disorder. Claes: “As a starting point, we used the results that were previously published by other teams about the genetic basis of such neuropsychiatric disorders. The possible link with the genes that determine the shape of our face had never been examined before. If you compare existing findings with our new ones, you see a relatively large overlap between the genetic variants that contribute to specific neuropsychiatric disorders and those that play a role in the shape of our brain, but not for those that contribute to our face.” In other words: our risk of developing a neuropsychiatric disorder is not written on our face either.
This research is a collaboration between KU Leuven, Stanford University School of Medicine, University of Pittsburgh, Pennsylvania State University, Indiana University Purdue University Indianapolis, Cardiff University, and George Mason University.
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Nearly 40,000 kids who lost a parent to COVID-19 need immediate support

Approximately 40,000 children in the United States may have lost a parent to COVID-19 since February 2020, according to a statistical model created by a team of researchers. The researchers anticipate that without immediate interventions, the trauma from losing a parent could cast a shadow of mental health and economic problems well into the future for this vulnerable population.
In the researchers’ model, for approximately every 13th COVID-related death, a child loses one parent. Children who lose a parent are at higher risk of a range of problems, including traumatic prolonged grief and depression, lower educational attainment, economic insecurity and accidental death or suicide, said Ashton Verdery, associate professor of sociology, demography and social data analytics and Institute for Computational and Data Sciences co-hire, Penn State.
“When we think of COVID-19 mortality, much of the conversation focuses on the fact that older adults are the populations at greatest risk. About 81% of deaths have been among those ages 65 and older according to the CDC (Centers for Disease Control and Prevention),” said Verdery, who is also an affiliate of the Population Research Institute at Penn State. “However, that leaves 19% of deaths among those under 65 — 15% of deaths are among those in their 50s and early 60s and 3% are among those in their 40s. In these younger age groups, substantial numbers of people have children, for whom the loss of a parent is a potentially devastating challenge.”
Three-quarters of the children who lost a parent are adolescents, but one quarter are elementary-aged children, Verdery said.
The statistics of parental death are grimmer for Black families, which have been disproportionately impacted by the pandemic, according to the researchers, who report their findings in today’s (April 5) issue of JAMA Pediatrics. The team estimated that 20% of the children who lost a parent are Black even though only 14% of children in the U.S. are Black.
The model also suggests that parental deaths due to COVID-19 will increase the country’s total cases of parental bereavement by 18% to 20% over what happens in a typical year, further straining an already stretched system that does not connect all children who are eligible to adequate resources.

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Scientists scour genes of 53,000+ people to better battle dangerous diseases

A new analysis of the entire genetic makeup of more than 53,000 people offers a bonanza of valuable insights into heart, lung, blood and sleep disorders, paving the way for new and better ways to treat and prevent some of the most common causes of disability and death.
The analysis from the Trans-Omics for Precision Medicine (TOPMed) program examines the complete genomes of 53,831 people of diverse backgrounds on different continents. Most are from minority groups, which have been historically underrepresented in genetic studies. The increased representation should translate into better understanding of how heart, lung, blood and sleep disorders affect minorities and should help reduce longstanding health disparities.
“The Human Genome Project has generated a lot of promises and opportunities for applying genomics to precision medicine, and the TOPMed program is a major step in this direction,” said Stephen S. Rich, PhD, a genetics researcher at the University of Virginia School of Medicine who helped lead the project. “An important feature of TOPMed is not only publishing the genomic data on 53,000 people with massive amounts of data related to heart, lung, blood and sleep disorders but also the great diversity of the participants who donated their blood and data.”
Historic Genome Analysis
The groundbreaking work identified 400 million genetic variants, of which more than 78% had never been described. Nearly 97% were extremely rare, occurring in less than 1% of people. This sheds light on both how genes mutate and on human evolution itself, the researchers say.
Of the groups studied, people of African descent had the greatest genetic variability, the researchers found. The resulting data is the best ever produced on people of African ancestry, the scientists report in the journal Nature.
The work also offers important new insights into certain gene variants that can reduce people’s ability to benefit from prescription drugs. This can vary by race and ethnic group.
“TOPMed is an important and historic effort to include under-represented minority participants in genetic studies,” said Rich, who served on the project’s Executive Committee and chaired the Steering Committee. “The work of TOPMed should translate not only into better scientific knowledge but increase diversity at all levels — scientists, trainees, participants — in work to extend personalized medicine for everyone.”
Rich was joined in the effort by UVA’s Ani Manichaikul, PhD; Joe Mychaleckyj, DPhil; and Aakrosh Ratan, PhD. All four are part of both the Center for Public Health Genomics and UVA’s Department of Public Health Sciences.
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New blueprint of brain connections reveals extensive reach of central regulator

Thousands of our daily activities, from making coffee to taking a walk to saying hello to a neighbor, are made possible through an ancient collection of brain structures tucked away near the center of the cranium.
The cluster of neurons known as the basal ganglia is a central hub for regulating a vast array of routine motor and behavior functions. But when signaling in the basal ganglia is weakened or broken, debilitating movement and psychiatric disorders can emerge, including Parkinson’s disease, Tourette’s syndrome, attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder.
Despite its central importance in controlling behavior, the specific, detailed paths across which information flows from the basal ganglia to other brain regions have remained poorly charted. Now, researchers at the University of California San Diego, Columbia University’s Zuckerman Institute and their colleagues have generated a precise map of brain connectivity from the largest output nucleus of the basal ganglia, an area known as the substantia nigra pars reticulata, or SNr. The findings offer a blueprint of the area’s architecture that revealed new details and a surprising level of influence connected to the basal ganglia.
The results, spearheaded by Assistant Project Scientist Lauren McElvain and carried out in the Neurophysics Laboratory of Professor David Kleinfeld at UC San Diego, and the laboratory of Zuckerman Institute Principal Investigator Rui Costa, are published April 5 in the journal Neuron.
The research establishes a new understanding of the position of the basal ganglia in the hierarchy of the motor system. According to the researchers, the newly identified pathways emerging from the connectivity map could potentially open additional avenues for intervention of Parkinson’s disease and other disorders tied to the basal ganglia.
“With the detailed circuit map in hand, we can now plan studies to identify the specific information conveyed by each pathway, how this information impacts downstream neurons to control movement and how dysfunction in each output pathway leads to the diverse symptoms of basal ganglia diseases,” said McElvain.
With support from the NIH’s Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, the researchers developed the new blueprint working in mice by applying a modern neuroscience toolset that combines techniques from genetics, virus tracing, automated microscopic imaging of whole-brain anatomy and image processing. The results revealed surprising new insights about the breadth of connections.
“These results are an example of how researchers supported by the BRAIN Initiative are using the latest brain mapping tools to change in a fundamental way our understanding of how the connections in the brain’s circuits are organized,” said John J. Ngai, director of the NIH’s BRAIN Initiative.
Previous work had emphasized that the basal ganglia architecture is dominated by a closed-loop with output projections connecting back to input structures. The new study reveals the SNr broadcasts even to lower levels of the motor and behavior system. This includes a large set of brainstem regions with direct connections to the spinal cord and motor nuclei that control muscles via a small number of intervening connections.
“The new findings led by Dr. McElvain offer an important lesson in motor control,” said Kleinfeld, a professor in the Division of Biological Sciences (Section of Neurobiology) and Division of Physical Sciences (Department of Physics). “The brain does not control movement though a hierarchy of commands, like the ‘neural networks’ of self-driving cars, but through a scheme of middle management that directs motor output while informing the executive planners.”
Remarkably, according to the researchers, the SNr neurons that project to the low levels of the motor system have branched axons that simultaneously project back up to the brain regions responsible for higher-order control and learning. In this way, the newly described connectivity of SNr neurons fundamentally links operations across high and low levels of the brain.
“The fact that specific basal ganglia output neurons project to specific downstream brain nuclei but also broadcast this information to higher motor centers has implications for how the brain chooses which movements to do in a particular context, and also for how it learns about which actions to do in the future,” said Costa, a professor of neuroscience and neurology at Columbia’s Vagelos College of Physicians and Surgeons, as well as director and chief executive officer of the Zuckerman Institute.

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