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WASHINGTON, D.C, (April 29, 2021) - An analysis of growth patterns in transcatheter aortic valve replacement (TAVR) programs across United States hospitals is being presented as late-breaking clinical science at the Society for Cardiovascular Angiography& Interventions (SCAI) 2021 Scientific Sessions. The findings indicate that TAVR hospital programs are predominately located in metropolitan areas serving patients with higher socioeconomic status, potentially contributing to the disparities in cardiac care.

TAVR is a minimally invasive procedure for patients in need of a valve repair or replacement and is an alternative to surgical aortic valve replacement (SAVR), a treatment option requiring open heart surgery. TAVR also provides eligible patients with quicker procedure times and a shorter recovery. Yet, despite the benefits of novel therapeutics such as TAVR, some patients are still referred to SAVR even if they are ideal candidates - prompting a deeper analysis of how the technology is disseminated in certain populations.

The study involved a cross-sectional analysis of Medicare claims data between January 1, 2012 to December 31, 2018. Linear regression models were used to compare socioeconomic characteristics of patients treated at hospitals that did and did not establish TAVR programs to determine the association between area-level markers of socioeconomic status and TAVR rates.

The findings reveal inequitable access to TAVR programs for non-metropolitan or lower income areas across the country. Between 2012 and 2018, 554 hospitals developed new TAVR programs including 543 (98.0%) in metropolitan areas, and 293 (52.9%) in metropolitan areas with pre-existing TAVR programs. Compared with hospitals that did not start TAVR programs, hospitals that did start TAVR programs treated patients with higher median household incomes (difference $1,305, 95% CI $134 to $12,477, p=0.03). Furthermore, TAVR rates per 100,000 Medicare beneficiaries were higher in areas with higher median income, despite adjusting for age and clinical comorbidities.

"TAVR has the potential to be an innovative and effective treatment option for heart valve patients, but can only work to its full potential if all patients have access to it. Our study results show a gap, and as clinicians, we know that these inequities can unfortunately translate into differing outcomes," said Ashwin Nathan MD, Fellow, Cardiovascular Medicine, Hospital of the University of Pennsylvania. "While this is just one example of health inequities, our hope is that these findings will activate a change in how we introduce high-tech solutions, so that all communities can access the care they need."

The authors also acknowledge that increasing access to TAVR and structural heart programs will require foresight into how clinical trials and approval for procedures and technologies at hospitals are distributed.

Improved Desalination Process Also Removes Toxic Metals to Produce Clean Water

-Adapted from UC Berkeley news release by Bob Sanders

Desalination - the removal of salt - is only one step in the process of producing drinkable water, or water for agriculture or industry, from ocean water or wastewater. Either before or after the removal of salt, the water often has to be treated to remove boron, which is toxic to plants, and heavy metals like arsenic and mercury, which are toxic to humans. Often, the process leaves behind a toxic brine that can be difficult to dispose of.

Now, a UC Berkeley-led research team in collaboration with Berkeley Lab has discovered a way to simplify the removal of toxic metals, like mercury and boron, during desalination to produce clean water, while at the same time potentially capturing valuable metals, such as gold. The study was recently published in the journal Science.

The new technique, which can easily be added to current membrane-based electrodialysis desalination processes, removes nearly 100% of these toxic metals, producing a pure brine along with pure water and isolating the valuable metals for later use or disposal.

Lead author Adam Uliana, a UC Berkeley graduate student, and senior author Jeffrey Long- a faculty scientist in Berkeley Lab's Materials Sciences Division and UC Berkeley chemistry professor, collaborated closely with Ngoc Bui, then a postdoctoral researcher in Berkeley Lab's Molecular Foundry and now an Assistant Professor at the University of Oklahoma, and Jeff Urban, director of the Molecular Foundry's Inorganic Nanostructures facility, to develop and implement the project.

"Virtually every element in the periodic table can be found in water, and being able to perform precise separations of critical elements is essential for achieving meaningful resource recovery," said Urban, who along with Bui pioneered a water-remediation technology called ZIOS that captures copper from wastewater with unprecedented atomic precision. "Performing remediation in concert with recovery would represent a huge step forward for water and energy technologies."

This work was supported by the National Science Foundation, and the Department of Energy's Office of Science and Laboratory Directed Research and Development (LDRD) Program.

Read the full UC Berkeley release here.

Infant-Warming Device Proven Effective and Safe in Reducing Neonatal Mortality

-By Kiran Julin

Newborn babies, particularly those born under-weight or preterm, are susceptible to hypothermia, since newborns are not yet able to maintain their own body heat. Hypothermia is recognized to be a significant contributor to newborn disease and death, particularly in low- and middle-income countries.

The World Health Organization and public health leaders have recommended best practices to prevent hypothermia in newborns. These include skin-to-skin contact with the mother, and if available, a supplemental external heat source. A new infant-warming device developed at Berkeley Lab and UC Berkeley offers a promising solution that does not require electricity, and is low-cost, convenient, and reusable.

A recent study in The Lancet found that the infant-warming device, known as the Dream Warmer, proved to be safe and effective at significantly lowering newborn mortality rates associated with hypothermia in Rwanda. The findings from a field trial led by Harvard Medical School showed that use of the infant warmer resulted in a drop in infant mortality from 2.8% to 0.9% in hospitals in Rwanda.

The Dream Warmer is a wrap-around pad containing a phase-change material, which is a substance that can absorb and release large amounts of thermal energy or heat when it melts or freezes. The Dream Warmer maintains a temperature of 98.6 degrees Fahrenheit, the average 020202boiling water and allowed to cool prior to use with newborn infants.

The technology was developed by Berkeley Lab scientists Ashok Gadgil and Vi Rapp, and builds upon an earlier design by Mike Elam, Jonathan Slack, and others at Berkeley Lab and UC Berkeley.

Gadgil and Rapp expected to see some effect on infant mortality but were thrilled to see the threefold drop. "That was a huge and quite unexpected result," said Gadgil.

"These results demonstrate the effectiveness and safety of the warmer, which will support its progression to an article of routine widespread use, first in Rwanda and then elsewhere," added Rapp.

The Harvard Medical School trial in Rwanda was conducted in collaboration with researchers at Berkeley Lab and UC Berkeley, and physicians at Partners in Health, Boston Children's Hospital, and the Rwanda Ministry of Health. The field research in Rwanda was funded by the Banyan Gates Foundation.

New Cuff-Based Technology Monitors Endothelial Function to Aid Prevention, Treatment of Heart Disease

-By Ruby Barcklay

Blood pressure monitors are a common at-home tool for monitoring heart health, but they don't look at the health of the endothelium, the lining of the blood vessels. And endothelial function is a powerful predictor of heart attack and stroke. It has also been linked to COVID-19 in a number of studies.

The trouble is, the current state-of-the-art method to monitor endothelial health, flow-mediated dilation (FMD), which measures the change in diameter in the brachial artery before and after shutting off blood flow, requires the use of an ultrasound scanner or expensive systems. The cost of these systems, and the technical skills needed to perform the measurement preclude frequent testing or continuous monitoring. And some FMD systems that are based on microvascular tone aren't always accurate, as they are sensitive to "sympathetic nervous activation," which can confound the results.

Berkeley Lab has developed a technology using cuffs, like those used for taking blood pressure, to monitor both endothelial function and endothelium-independent vasodilation. Studies on human subjects have verified that the cuff-based method is 37% more sensitive to arterial relaxation than brachial artery imaging. In addition, the apparatus costs one-fifteenth as much as an ultrasonic imager and eliminates the need for an ultrasound technician.

The lower cost and non-invasive method allows for routine detection and monitoring of endothelial health. That means earlier identification of cardiovascular disease and closer management of endothelial health.

"The cuffs are similar to the blood pressure devices many people already use," said bioscientist Jonathan Maltz, who developed the technology with fellow bioscientist Thomas Budinger. "With this technology, people can regularly monitor their endothelial health, in addition to their blood pressure, either at the doctor's office or in the comfort of their own homes."

Maltz also invented a way to calibrate the cuff-based measurements with those of ultrasound-based flow-mediated dilation. The calibrations allow health providers to monitor the effects of interventions such as exercise, smoking cessation, dietary modification, and cholesterol-lowering therapy, on patient health.

The Berkeley Lab technology is now available for licensing.

Meteorites Reveal Magnetic Record of Protoplanet Churn

-By Lori Tamura

If you stumble upon an unusual rock that could be a meteorite, do not place a magnet on it to see if it's magnetic - you'd end up erasing 4.5 billion years of magnetic history. Meteorites are remnants of our solar system's first protoplanets and, in some cases, retain a record of the magnetic fields they've experienced in the distant past.

"As planetary scientists, we're interested in understanding how protoplanets formed and evolved prior to the formation of the planets we know today," said Clara Maurel, a Ph.D. student at MIT's Department of Earth, Atmospheric, and Planetary Sciences. "There are many different areas of research that tackle these questions, and our angle of approach is to use magnetism."

In a recent paper published in the journal Geophysical Research Letters, Maurel and colleagues from MIT, Oxford, Arizona State, NASA's Jet Propulsion Laboratory, and Berkeley Lab detected the signatures of ancient magnetic fields imprinted in a meteorite's ferromagnetic grains at Berkeley Lab's Advanced Light Source (ALS).

The results revealed a bias in the magnetization directions found in different regions of the sample, indicating that the meteorite was exposed to a substantial, stable magnetic field that magnetized its ferromagnetic grains upon cooling. The team interpreted this as evidence for a dynamo-generated magnetic field powered by the parent body's churning, molten-metal core. A similar mechanism powers the Earth's magnetic field today.

Combined with earlier measurements of two other meteorites from the same parent and radioisotopic dating of the samples, the results support an extended time frame for the cooling of molten protoplanetary cores. Despite its small size compared to planets, this protoplanet did not cool quickly, but instead sustained a molten metallic core for tens of millions of years after the birth of the solar system.

"For people who are interested in modeling the evolution of protoplanets, experimental constraints like this are essential," said Maurel. "These data points represent an important first step toward a better understanding of the chronological activity of protoplanets, from their formation to the time they completely solidify and become inactive."

Lacticaseibacillus rhamnosus GG, or LGG, is the most studied probiotic bacterium in the world. However, its features are not perfect, as it is unable to utilise the milk carbohydrate lactose or break down the milk protein casein. This is why the bacterium grows poorly in milk and why it has to be separately added to probiotic dairy products.

In fact, attempts have been made to make L. rhamnosus GG better adjust to milk through genetic engineering. However, strict restrictions have prevented the use of such modified bacteria in human food.

Thanks to a recent breakthrough made at the University of Helsinki, Finland, with researchers from the National Institute for Biotechnology and Genetic Engineering, Pakistan, features have now been successfully added to the LGG probiotic without gene editing, making it thrive and grow in milk.

The method used is known as conjugation, which is a technique utilised by certain bacterial groups to transfer their traits to other bacteria. In the process, a bacterium produces a copy of its plasmid, a ring-shaped piece of DNA in the bacterium. Next, the bacterium transfers the plasmid to an adjacent bacterium. The spread of plasmids, which carry traits useful for bacteria, can be rapid among bacterial communities.

In the case of Lacticaseibacillus rhamnosus GG, the plasmid that provided the ability to make use of lactose and casein originated in a specific Lactococcus lactis bacterial strain grown in the same place.

"The new LGG strain is not genetically modified, which makes it possible to consume it and any products containing it without any permit procedures," says the project leader, Professor of Microbiology Per Saris from the Faculty of Agriculture and Forestry, University of Helsinki.

The new strain can be used as a starting point in the development of new dairy products where the probiotic concentration increases already in the production stage. In other words, the probiotic need not be separately added to the final product.

Furthermore, the new LGG strain can potentially be better equipped to grow, for example, in the infant gut where it would be able to utilise the lactose and casein found in breastmilk, producing more lactic acid than the original strain.

"Lactic acid lowers the pH of the surface of the intestine, reducing the viability of many gram-negative pathogenic bacteria, such as E. coli, Salmonella and Shigella, which threaten the health of infants. Moreover, in larger numbers the new LGG strain can potentially be more effective at protecting infants than the old strain. After all, LGG has previously been shown to alleviate infantile atopic dermatitis and boost the recovery of the gut microbiota after antibiotic therapies."

The researchers are in negotiations on the further application of their discovery.

A third of children and adolescents develop a mental health problem after a concussion, which could persist for several years post-injury, according to a new literature review.

The research, led by the Murdoch Children's Research Institute (MCRI) and published in the British Journal of Sports Medicine, found mental health should be evaluated as part of standard pediatric concussion assessment and management.

MCRI researcher and Monash University PhD candidate Alice Gornall said despite many post-concussion and mental health symptoms overlapping, the relationship between delayed recovery and mental health had remained poorly understood until this literature review.

The review of 69 articles published between 1980 to June 2020, involved almost 90,000 children, aged 0-18 years, from nine countries including Australia, US, Canada and New Zealand, who had a concussion. Falls (42.3 per cent) and sporting injuries (29.5 per cent) were the most common cause of injury, followed by car accidents (15.5 per cent).

It found up to 36.7 per cent experienced significantly high levels of internalising problems such as withdrawing, anxiety, depression and post-traumatic stress and 20 per cent externalising problems such as aggression, attention problems and hyperactivity after concussion compared with healthy children or children who sustained other injuries such as an arm fracture.

Pre-existing mental health problems were a strong predictor of post-concussion mental health issues. The review stated 29 per cent of children with a pre-injury mental health diagnoses received a new mental health diagnosis post-concussion. Up to 26 per cent without prior mental health problems went onto develop symptoms.

Ms Gornall said while significant improvements in mental health emerged between three and six months post-injury, a minority of children experienced persisting symptoms for several years afterwards.

The findings come after a recent study, led by MCRI and published in The Journal of Head Trauma Rehabilitation, found having a traumatic brain injury in early childhood was associated with lower IQ scores that persist up to seven years post-injury.

Ms Gornall said concussion was a growing public health concern with a third of children experiencing a head injury before 13 years of age.

"Despite the high incidence of concussion among children and adolescents, identifying those at risk of ongoing difficulties after concussion remains a prominent challenge for clinicians," she said.

"On top of this, children take twice as long to recover from concussion than adults, with one in four children experiencing symptoms beyond one-month post-injury."

Melbourne resident Emma, 17, has been seeking mental health support after suffering two concussions, a year apart.

In 2019 while playing netball she knocked her head on a goal post and last March she was hit with a ball in the back of the head.

Emma said after the second concussion she developed anxiety, headaches, a sense of hopelessness and had trouble concentrating.

"After my last concussion I found it very hard to be motivated for school and everyday life. Doing the simplest of tasks such as a walk was difficult for me, not being able to complete these tasks got me quite disheartened which impacted on my mental health," she said.

Emma's dad Bruce Henry said he welcomed the push for mental health to be part of paediatric concussion assessment and management as many cases would be going untreated.

"When a child has a concussion they might look fine but you can't see the underlying impact," he said. It's so important for mental health to form part of concussion management, which has been essential to Emma's recovery process."

MCRI researchers are also trialling an intervention, Concussion Essentials, to prevent children suffering long term post-concussion symptoms.

The eight session intervention combines physiotherapy and psychology treatments that target presenting symptoms with education around common concerns such as headache, fatigue and return to exercise, school and sports. Early data shows that the intervention is effective in accelerating recovery.

MCRI Professor Vicki Anderson said assessment, prevention and intervention of mental health difficulties after concussion should be integrated into standard concussion management.

"Mental health is central to concussion recovery. Concussion may both precipitate and exacerbate mental health difficulties, impacting delayed recovery and psychosocial outcomes," she said.

"Incorporating mental health risk into post-injury management represents an opportunity to engage children and adolescents with mental health services to either prevent unnecessary problems emerging or to treat already existing issues."

Developed by world-leading concussion experts at MCRI and The Royal Children's Hospital and in collaboration with the AFL, the HeadCheck app also helps parents, coaches and first aiders to recognise the signs of concussion and manage the child's safe return to school, play and organised sport.

A collaboration between experts and a Danish-based, global reaching patient organization has resulted in a groundbreaking medical publication, where guidelines are being presented on how to manage patients with unexplained low blood sugar.

Danielle Drachmann, founder of Ketotic Hypoglycemia International (KHI), spent years being dismissed by doctors due to the outdated perception that her children's dangerous low blood glucose (sugar) and high ketone levels were a normal variation.

Professor Henrik Christesen, Head of the Complex Hypoglycemia Center, Odense University Hospital, Denmark, could not identify the cause of the condition despite intense efforts, but recognized the severity of the children's condition and implemented strict monitoring and management guidelines to support the family.

Closing the gap: Uniting the patients and the experts

Henrik and Danielle shared frustrations due to the lack of knowledge of severe, unexplained ("idiopathic") ketotic hypoglycemia across the wider medical field.

This led Danielle to establish Ketotic Hypoglycemia International with Professor Christesen leading the Scientific Advisory Board.

The patient organization gathered leading experts from the fields of endocrinology and inborn errors of metabolism, uniting them with patient representatives from across the globe. The result is a shared publication in the international medical journal Orphanet Journal of Rare Diseases.

Low blood sugar in children is not just normal

For the first time since the term idiopathic ketotic hypoglycemia was coined in 1964, the the condition is now being divided in two, a physiological and a pathological (severe) form.

The key message is that pathological ketotic hypoglycemia of unknown cause is more than normal variation in small children. Pathological ketotic hypoglycemia should be diagnosed and treated as any other disease, according to the authors.

"The problem is that an old perception of ketotic hypoglycemia just being a normal variation of childhood has kept children from getting the medical investigations and help they need. The medical textbooks must be rewritten" Professor Christesen states.

Parents and experts are excited

With this paper, the severity-range of the condition has been recognized and family members are labeling the news of the upcoming paper as life changing;

"Multiple seizures and ER visits, and we are still being told that this is normal for children. The news of the paper gives me hope that Ketotic Hypoglycemia International has started a revolution. Hope for my child's future and hope that our voices are finally going to be heard," proclaims Victoria, a KHI group member from the United States.

Hypoglycemia expert Dr. David Weinstein, the former director of the Glycogen Storage Disease Program in the US and co-author of the paper, states;

"These children deserve to get answers and they deserve proper treatment. My one regret is that I never was able to get the medical field to take ketotic hypoglycemia seriously."

Be a part of the revolution

Ketotic hypoglycemia is placed somewhere between the two expert fields, pediatric endocrinology and inborn metabolic diseases, as a real orphan disease. The new patient organization has succeeded in bringing experts from the two different medical fields together in this publication.

On top of giving guidelines for diagnosis and treatment, the new patient organization, Ketotic Hypoglycemia International, is presented in the paper.

The organization urges all medical professionals to increase their knowledge and improve their clinical practice by reading this crucial publication about ketotic hypoglycemia,

The organization aims to help this misunderstood patient-group gain access to critical medical supplies, referrals to specialist providers and finally receive the professional validation that their symptoms warrant a full investigation.

"It's been a fantastic journey from feeling alone with two untreated children to become recognized together with hundreds of other families as having a real disease that deserves treatment", first author Danielle Drachmann says.

Facts about ketotic hypoglycemia

In ketotic hypoglycemia, the glucose metabolism works poorly, which is why the body switches to fat burning more quickly. The poor glucose metabolism results in low blood sugar (hypoglycemia) and the increased fat metabolism results in ketone bodies such as acetone. A patient can therefore directly smell of acetone if he or she has an attack of ketotic hypoglycemia. Both sugar and fat burning are enzymatic processes controlled by a number of hormones. In order to have unexplained (idiopathic) ketotic hypoglycemia, a number of enzyme defects in cell metabolism and a number of hormonal diseases must be ruled out. However, an explanation can be found in some of the patients if the cases are being investigated thoroughly, including major genetic analysis packages.

Over the past ten years, Henrik Christesen has met about 100 children with ketotic hypoglycemia and 15 parents who also had the condition in adulthood. Based on the new research, he estimates that 150 new children and adults annually need medical investigation due to hypoglycemia in Denmark alone.

Toxic pollution hits poorer populations hardest as firms experience more pollutant releases and spend less money on waste management in areas with lower average incomes.

Research from Lancaster University Management School and Texas Tech University, published in European Economic Review looked into the relationship between the location choices of potentially polluting firms and levels of local income to discover if firms made strategic decisions on site locations based on population demographics.

The team studied potentially polluting firms across Texas, and found a correlation between lower income locations and the probability of potentially polluting firms choosing to locate there. Their data, from the US Environment Agency's Toxic Release Inventory also showed the relative frequency of toxic releases decreased as household income rose.

"We looked both at whether firms made decisions on their location based on demographics - particularly income - of the local areas, and also whether firms made different choices on limiting the possibilities of toxic release through waste management based on those same statistics," said co-author Professor Dakshina De Silva, of Lancaster University's Department of Economics.

"Firms reduced their releases and increased spending on waste management in higher income areas - evidenced by a greater number of waste management services - while lower income areas were disproportionately subject to toxic releases.

"The patterns we observed lead us to conclude that, at least partially, potentially polluting firms seek to maximise their expected profits and recognise the financial risk associated with a release in different areas."

Releasing toxic chemicals in the environment is costly for firms because they will have to implement clean-up programmes, pay penalties and compensate local residents for damages. Higher incomes - and associated property values - increase the costs as damages are linked to reduced property values and lost income due to limitations on working.

"Potentially polluting firms seeking to maximise profits will be concerned with the liability of toxic releases and the threat such releases pose to their financial results," said co-author Dr Anita Schiller, of Lancaster University. "They will therefore take into account the demographics of an area when valuing the legal costs and compensation they would have to pay out in the event of a toxic release, and balance this with the cost of reducing the likelihood of such a release.

"In areas where there is a higher income and higher property prices, compensation levels will go up in the event of an incident, with the possibility of collective action by residents and businesses also increasing. Potentially polluting firms must also consider the financial risk of a release and the costs of managing such an incident's likelihood."

The researchers found that levels of toxic release had declined steadily since 2000 - by 34% between 2000 and 2006 and by a further 21% since 2006 - but suggested this drop was not uniform, with potentially polluting firms reducing releases through waste management where local opposition to their presence was the highest.

Co-author Dr Aurelie Slechten added: "Combined with our finding that economic activity and local income are linked with spending on waste management and with levels of toxic releases, this implies that the group most affected by releases will be poorer populations in industrial areas.

"Without further action, the disparity in exposure to toxic releases faced by certain groups will not be reduced by simply requiring that firms report their releases. Serious thought needs to be given to regulation on compensation schemes."

Coral reefs provide shelter, sustenance and stability to a range of organisms, but these vital ecosystems would not exist if not for the skeletal structure created by stony corals. Now, KAUST scientists together with an international team have revealed the underlying genetic story of how corals evolved from soft-bodied organisms to build the myriad calcified structures we see today.

"While the processes involved in coral calcification are well understood, it is less clear how corals' ability to grow calcium carbonate skeletons actually evolved," says Xin Wang, a former KAUST Ph.D. student who worked on the project under the supervision of Manual Aranda.

"How did a squishy anemone-like organism begin to build reefs?" asks Aranda. "Did the 'tools' already exist in their genetic code?"

There is a debate surrounding when calcified corals first began to emerge; the earliest fossils found to date are around 265 million years old, but their evolution began far earlier.

"We conducted a genomic search for conserved genes that might be involved in calcification," says Wang. "Our findings suggest that corals evolved to calcify somewhere between 308 and 265 million years ago."

The team compared the genomes of six different related species -- two evolutionary divergent reef-building corals, two of their closest noncalcifying relatives and two sea anemones. The complex analysis took two years using the KAUST supercomputer.

"We found that the necessary proteins to make coral skeletons were already present in the soft-bodied ancestor and that various existing proteins were recruited to boost the calcifying process. Essentially, we believe we've found the genetic toolkit for coral skeleton creation," says Wang.

To calcify, corals must draw in positively charged calcium ions from seawater. To make this process as efficient as possible, the coral proteins that help the calcium precipitate should be negatively charged and the pH balance of the calcifying fluid must be just right.

The team pinpointed the genes responsible for transporting calcium and removing protons in the soft-bodied organisms, and they showed that two of the three gene copies found in corals have been recruited to the calcifying tissue. The researchers then identified a gene encoding an acid-rich protein that was duplicated in corals twice and then recruited to precipitate and stabilize calcium carbonate in the initial stage of skeleton building. They also highlighted transmembrane proteins involved in bone matrix adhesion.

"This is a great example of how latent traits can evolve to become dominant given certain environmental pressures," says Aranda. "Next we hope to verify which of these components is critical to calcification and investigate how coral reefs might be influenced by the changing pH of future oceans."

LAWRENCE -- Researchers commonly work with the criminal justice system to implement reforms, bringing with them the latest science and data pointing to why a certain practice will help improve outcomes. New research from the University of Kansas shows if community corrections agencies are to sustain evidence-based reforms, they need to view them as legitimate.

Researchers worked with eight federal community corrections agencies to implement Contingency Management, an evidence-based practice used to help people convicted of drug offenses set and achieve goals to end addiction, avoid repeat offenses and increase pro-social behavior. Such evidence-based practices and reforms are frequently put in place across the criminal justice system.

Shannon Portillo"We've seen millions of dollars spent by institutions on evidence-based practices in community corrections settings, but there is very little research on if the reforms stick after researchers leave," said Shannon Portillo, associate professor of public affairs & administration at KU and co-author of the study. "We followed up after our original study with community corrections agencies, and we found reform only sticks when staff viewed the reform as legitimate. It is not enough to show that reforms are effective or efficient. Workers must view them as legitimate and aligned with their organization's goals."

The study, co-written with Danielle Rudes and Faye Taxman of George Mason University, was published in the British Journal of Criminology.

The researchers returned to the eight community corrections sites five years after implementing Contingency Management. While all sites saw the reformed practices as legitimate enough to initially consider adoption, two sites never adopted them, four sites experimented with reform, and two sites continued to use the reform after the study was over. The research team evaluated the legitimacy of the reform on three levels: Pragmatic, or if staff recognized that the practice could fit with their site routines and operations; moral, or if it was viewed as the right thing to do to help their clients; and cognitive, or if they could understand how this reform was different from current practices and was a shift in behaviors that could fit their agency.

Results showed that sites that sustained Contingency Management rated it moderately or strongly in all three areas but that it had to be viewed strongly in terms of cognitive legitimacy. Sites in which it was not sustained gave various reasons for scoring it lower; for example, one employee did not use the software provided to keep track of data, instead logging it manually and reporting it was additional work, resulting in a low score in pragmatic legitimacy. Leadership was key in implementing reforms but could not make others view them as legitimate simply by requiring staff to implement the new practice. In fact, leadership views of legitimacy, efficiency and effectiveness of the measure was not a key factor at all, compared to staff views of legitimacy.

"This shows it really had to be the workers who saw this change as worthwhile and saw how the reform was worth their time to change their behaviors and workplace practices," Portillo said.

In some of the sites where the evidence-based practice was not sustained, workers and management discussed the reform, but they indicated they were not sure exactly what it meant or how they could find a way to make it fit in their operations, meaning it did not score well in cognitive or pragmatic legitimacy. Contingency management works by helping individuals set goals for recovery, meet requirements set in terms of their probation or by courts and rewarding them with gift cards or points toward purchases when certain benchmarks are met.

"It sounds simple, but this is a huge shift in mindset for the criminal justice system, because the system is so punishment-oriented. So, it was not always viewed as legitimate," Portillo said.

Presenting such a fundamental change in operations shows that reform cannot be implemented or sustained without demonstrating to those tasked with carrying it out of its value. Demonstrating the efficacy or leadership simply telling workers it is something they have to do was not enough. While much effort and money have been invested in criminal justice reform, a deeper understanding of what reforms work as well as how to make them stick is vital to improving the criminal justice system and helping individuals successfully transition back to society.

"This is definitely an area that needs more research, as the federal government invests a lot, and individual organizations invest a lot of time and resources in reforms and evidence-based practices," Portillo said. "We need to know more about how reform can be successful and how it is sustained for the long term."

Nanopore technology shows promise for making it possible to develop small, portable, inexpensive devices that can sequence DNA in real time. One of the challenges, however, has been to make the technology more accurate.

Researchers at The University of Texas at Dallas have moved closer toward this goal by developing a nanopore sequencing platform that, for the first time, can detect the presence of nucleobases, the building blocks of DNA and RNA. The study was published online Feb. 11 and is featured on the back cover of the April print edition of the journal Electrophoresis.

"By enabling us to detect the presence of nucleobases, our platform can help improve the sensitivity of nanopore sequencing," said Dr. Moon Kim, professor of materials science and engineering and the Louis Beecherl Jr. Distinguished Professor in the Erik Jonsson School of Engineering and Computer Science.

Currently, most DNA sequencing is done through a process that involves preparing samples in the lab with fluorescent dye and using lasers to determine the sequence of the four nucleobases, the fundamental units of the genetic code: adenine (A), cytosine (C), guanine (G) and thymine (T). Each nucleobase emits a different wavelength when illuminated, allowing scientists to determine the sequence.

In nanopore sequencing, a DNA sample is uncoiled, and the hairlike strand is fed through a tiny hole, or nanopore, typically in a fabricated membrane. As it moves through the nanopore, the DNA strand disturbs the electrical current flowing through the membrane. The current responds differently based on the characteristics of a DNA molecule, such as its size and shape.

"The electrical signal changes as the DNA moves through the nanopore," Kim said. "We can read the characteristics of the DNA by monitoring the signal."

One of the challenges in advancing nanopore sequencing has been the difficulty of controlling the speed of the DNA strand as it moves through the nanopore. The UT Dallas team's research focused on addressing that by fabricating an atomically thin solid-state -- or nonbiological -- membrane coated with titanium dioxide, water and an ionic liquid to slow the speed of the molecules through the membrane. The water was added to the liquid solution to amplify the electrical signals, making them easier to read.

"By enabling us to detect the presence of nucleobases, our platform can help improve the sensitivity of nanopore sequencing."

The next step for researchers will be to advance the platform to identity each nucleobase more quickly. Kim said the platform also opens possibilities for sequencing other biomolecules.

"The ultimate goal is to have a hand-held DNA sequencing device that is fast, accurate and can be used anywhere," Kim said. "This would reduce the cost of DNA sequencing and make it more accessible."

A study by University of Guam researchers has found that shade can mitigate the effects of heat stress on corals. The study, which was funded by the university's National Science Foundation EPSCoR grant, was published in February in the peer-reviewed Marine Biology Research journal.

"We wanted to see what role light has in coral bleaching," said UOG Assistant Professor Bastian Bentlage, the supervisor and co-author of the study. "Usually, people talk about temperature as a cause for bleaching, but we show that both light and temperature work together."

Previous UOG research led by Laurie J. Raymundo found that more than one-third of all coral reefs in Guam were killed from 2013 to 2017 over the course of multiple bleaching events. Coral bleaching is the process in which corals stressed by environmental changes expel the essential symbiotic algae that live in their tissues, causing them to turn white and often die.

This latest study examined the resilience of staghorn corals (Acropora cf. pulchra) in heightened seawater temperatures. This species of coral is one of Guam's dominant reef-builders, and its habitats experience temperatures up to 97 degrees Fahrenheit during the hottest months of the year, leaving it vulnerable to bleaching episodes and population decline.

A team of researchers -- including lead author Justin T. Berg, a UOG graduate student studying biology; Charlotte M. David, an undergraduate student from the University of Plymouth (England), and Melissa Gabriel, a UOG graduate student studying environmental science -- took coral samples from the Hagåtña reef flat and examined their health in the UOG Marine Laboratory under normal and elevated temperatures.

"One group was subjected to consistent baseline temperatures observed on Guam's reef flats," Bentlage said, "and another was set to temperatures that are projected to become the new normal over the next couple of decades."

The researchers found that the corals took three weeks to recover from a week-long heat stress event. The experiment was then replicated to see how the corals would react if they were given shade while subjected to warmer temperatures.

"We found that when we put the shading over coral with increased seawater temperatures, it greatly increased photosynthetic yield of the symbiotic algae. Shade made a huge difference for coral health when you have high temperatures," Berg said.

Implications for reef management

Shading is a practice already used in coral nurseries, Bentlage said, but it may not be practical to shade whole reefs in the ocean. Future studies can look into practical ways to reduce the impact of light on corals, particularly as they recover from periods of elevated temperatures.

"We saw the corals recover rather slowly," Berg said. "The length of recovery indicates that corals are vulnerable during this time and management efforts may be particularly necessary during this period to reduce coral mortality."

Berg said the new knowledge may also help inform the best locations to successfully outplant corals.

"For example, slightly turbid waters could provide some shading to corals, making them less likely to bleach during periods of elevated sea surface temperatures," Berg said.

COLUMBUS, Ohio - Hispanic Americans have died of COVID-19 at a disproportionately high rate compared to whites because of workplace exposure to the virus, a new study suggests.

It's widely documented that Hispanics are overrepresented among workers in essential industries and occupations ranging from warehousing and grocery stores to health care and construction, much of which kept operating when most of the country shut down last spring.

The analysis of federal data showed that, considering their representation in the U.S. population, far higher percentages of Hispanics of working age - 30 to 69 years old - have died of COVID-19 than whites in the same age groups. A separate look at case estimates showed a similar pattern of unequally high COVID-19 infection rates for Hispanics - meaning that the elevated deaths in the working-age Hispanic population is consistent with elevated exposure to the virus.

"There was no evidence before this paper that really demonstrated that the excess cases were precisely in these working age groups," said Reanne Frank, professor of sociology at The Ohio State University and co-author of the study.

"Particularly for front-line and essential workers, among whom Hispanics are overrepresented, COVID-19 is an occupational disease that spreads at work. Hispanics were on the front lines and they bore a disproportionate cost."

Identifying a link between essential work and a higher rate of COVID-19 deaths should lead to better workplace protections, said study co-author D. Phuong (Phoenix) Do, associate professor of public health policy and administration at the University of Wisconsin-Milwaukee.

"If we know the source of the spread, then we can tackle it head on," she said. "This finding is applicable to any disease that is highly infectious. We can't stop the economy - we've learned that. There has to be a way to protect the workers and enforce protection."

All analyses were based on the most recent data as of Sept. 30, 2020. The research is published in the journal Demographic Research.

Because COVID-19 death rates are highest among older ages, the fact that a much higher percentage of Hispanics are in the younger age groups compared to whites meant that excess Hispanic deaths were initially masked. Centers for Disease Control and Prevention (CDC) age-adjusted data from 2020 showed that Hispanics constituted 19% of the population, but almost 41% of COVID-19 deaths.

When it became apparent that COVID-19 deaths were disproportionately high among minorities, commentators frequently suggested that unequal access to quality health care, higher levels of pre-existing conditions and multigenerational households were key causes, along with exposure as front-line workers.

At the time, however, "there wasn't any case data to support this workplace vulnerability hypothesis, which to us seemed most compelling in trying to understand the excess deaths among Hispanics," said Frank, also a faculty affiliate in Ohio State's Institute for Population Research.

Using CDC death counts stratified by age within racial/ethnic groups, the researchers compared the proportion of COVID-19 deaths attributed to whites and Hispanics with each group's relative population size. Nationally and in most states, in every range below age 75, Hispanic deaths were disproportionately high and deaths among whites were disproportionately low. One example from national data: Hispanics ages 35 to 44 and 55 to 64 experienced a higher-than-expected proportion of deaths of 15.4 and 8 percentage points, respectively. In contrast, whites in those same age groups faced mortality advantages of 23 and 17 percentage points, respectively.

Turning to CDC case surveillance data, the researchers found the same patterns at the county level. Overall and within each age group, whites were disproportionately underrepresented among COVID-19 cases, while Hispanics were overrepresented, with the greatest excess in cases among those of working age: 30 to 59.

Among the reported cases, Hispanics had fewer pre-existing health conditions than whites and there were no significant differences between working-age Hispanics and whites in the percentage of infections that resulted in death. Hence, the researchers said, the case data is not supportive of pre-existing comorbidities and/or lower-quality health care being driving factors in the excess Hispanic mortality.

"If case fatality rates are comparable across racial and ethnic groups, and they are, but we see big differences in the amount of death, which we do, then we have to focus on differential exposure," Do said. "So what we see is that these two patterns are consistent with higher case burden being the driving factor of the higher mortality burden among Hispanics.

"The evidence does not support the other hypotheses. The data in this case supported the workplace exposure hypothesis but not unequal access to health care or unequal quality of care, not pre-existing conditions, and not multigenerational household exposure."

The researchers said the patterns revealed in the data ideally will discourage what amounts to victim-blaming - attributing an unequally high rate of COVID-19 deaths among Hispanics to risks associated with individual health behaviors or living arrangements rather than their overrepresentation in the essential workforce, often in low-wage jobs.

"There's this impulse when we're trying to understand racial health disparities - even new ones like COVID that appeared very quickly - to obscure the role of structural factors, which includes work environments," Frank said. "This evidence can hopefully set the record straight about why the Hispanic community, along with other groups overrepresented among front-line workers, took such a heavy hit from this pandemic - that it was because they were doing their jobs, and putting themselves on the line."

#

Contacts:
Phoenix Do, dphuong@uwm.edu
Reanne Frank, frank.219@osu.edu

Written by Emily Caldwell, Caldwell.151@osu.edu

DALLAS - April 28, 2021 - Depression screening among cancer patients improved by 40 percent to cover more than 90 percent of patients under a quality improvement program launched by a multidisciplinary team at UT Southwestern Medical Center and Southwestern Health Resources.

Cancer patients with depression are at an increased risk of mortality and suicide compared with those without depression. Although rates vary based on cancer type and stage, depression is estimated to affect 10 to 30 percent of patients with cancer compared with 7 to 8 percent of adults without a diagnosis or history of cancer, and impact both men and women equally.

Due to the higher risk, medical and scientific authorities including the National Institutes of Health, the Institute of Medicine, and the National Comprehensive Cancer Network recommend routine screening to identify untreated symptoms of depression in cancer patients.

"Identifying those with depressive symptoms through earlier detection, diagnosis, and treatment can greatly improve the quality of life for these patients and their families, and prevent minor symptoms from progressing to severe psychopathology and potential self-harm," says Jason Fish, M.D., chief medical officer at Southwestern Health Resources and associate professor of internal medicine at UT Southwestern. "The findings from our study have the potential ability to not only positively impact treatment outcomes and slow disease progression, but to save health care resources."

A multidisciplinary team collaboratively applied Lean Six Sigma methods and tools among more than 14,000 oncology patients within oncology and psychiatry clinics in the Southwestern Health Resources network and at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center.

The ongoing quality improvement initiative enhanced screening and follow-up rates in individual clinics by more than 40 percent and achieved the project goal of reaching 90 percent of patients in fewer than six months, according to Fish, who oversees quality and performance improvement activities for Southwestern Health Resources, a clinically integrated health care network formed by UT Southwestern and Texas Health Resources. If the ending performance rate of 89.8 percent had been in effect at the beginning of the project, an additional 1,290 patients could have received screening in a single month, the authors wrote.

Considerable gap in evidence around whether portable air filters reduce the incidence of COVID-19 and other respiratory infections

There is an important absence of evidence regarding the effectiveness of a potentially cost-efficient intervention to prevent indoor transmission of respiratory infections, including COVID-19, warns a study by researchers at the University of Bristol.

Respiratory infections such as coughs, colds, and influenza, are common in all age groups, and can be either viral or bacterial. Bacteria and viruses can become airborne via talking, coughing or sneezing. The current global coronavirus (COVID-19) pandemic is also spread primarily by airborne droplets, and to date has led to over three million deaths worldwide.

Controlling how we acquire and transmit respiratory infections is of huge importance, particularly within indoor environments such as care homes, households, schools/day care, office buildings and hospitals where people are in close contact. Several manufacturers of portable air filters have claimed their products remove potentially harmful bacteria and viruses from indoor air, including COVID-19 viral particles. However, there is often no detailed evidence provided on their websites to corroborate their claims for potential consumers to review before purchasing.

A team of UK researchers from the University of Bristol reviewed previous studies to investigate whether portable air filters used in any indoor setting can reduce incidence of respiratory infections and thus, whether there is any evidence to recommend their use in these settings to reduce the spread of COVID-19 and other respiratory infections. The team also explored whether portable air filters in indoor settings capture airborne bacteria and viruses within them, and if so, what specifically is captured.

The researchers found no studies investigating the effects of portable, commercially available air filters on the incidence of respiratory infections in any indoor community setting. Two studies reported removal or capture of airborne bacteria in indoor settings (an office and emergency room), demonstrating that the filters did capture airborne bacteria and reduced the amount of airborne bacteria in the air. Neither tested for the presence of viruses in the filters, nor a reduction in viral particles in the air.

The study, funded by Professor Alastair Hay's National Institute for Health Research Senior Investigator Award and published in PLoS One, was a systematic review of studies published after 2000 reporting (i) effects of portable air filters on incidence of respiratory infection, or (ii) whether filters capture and/or remove aerosolised bacteria and viruses from the air, including information of what is captured. Studies reporting non-portable air filters were excluded from this study.

Lead author, Dr Ashley Hammond, an Infectious Disease Epidemiologist at the Centre for Academic Primary Care, University of Bristol, said: "Our study highlights the considerable gap in evidence related to the effectiveness of portable air filters in preventing respiratory infections, including COVID-19. Whilst we found some evidence suggesting use of air filters could theoretically contribute to reducing the spread of COVID-19 and other respiratory infections by capturing airborne particles, there is a complete absence of evidence as to whether they actually reduce the incidence of these infections."

Professor Alastair Hay, a GP and Professor of Primary Care at the Centre for Academic Primary Care, University of Bristol, and the research group lead, said: "Randomised controlled trials are urgently needed to demonstrate the effects of portable air filters on incidence of respiratory infections, including COVID-19. The main research questions should focus primarily on whether use of portable air filters in any indoor environment can reduce respiratory infections compared to those environments without portable air filters."

LAWRENCE -- For thousands of years during the last ice age, generations of maritime migrants paddled skin boats eastward across shallow ocean waters from Asia to present-day Alaska. They voyaged from island to island and ultimately to shore, surviving on bountiful seaweeds, fish, shellfish, birds and game harvested from coastal and nearshore biomes. Their island-rich route was possible due to a shifting archipelago that stretched almost 900 miles from one continent to the other.

A new study from the University of Kansas in partnership with universities in Bologna and Urbino, Italy, documents the newly named Bering Transitory Archipelago and then points to how, when and where the first Americans may have crossed. The authors' stepping-stones hypothesis depends on scores of islands that emerged during the last ice age as sea level fell when ocean waters were locked in glaciers and later rose when ice sheets melted. The two-part study, just published in the open-access journal Comptes Rendus Geoscience, may answer what writer Fen Montaigne calls "one of the greatest mysteries of our time . . . when humans made the first bold journey to the Americas."

The "stepping-stones" idea hinges on retrospective mapping of sea levels while accounting for isostacy -- deformation of the Earth's crust due to the changing depth and weight of ice and water, reaching its greatest extreme during the Last Glacial Maximum about 20,500 years ago.

"We digitally discovered a geographic feature of considerable size that had never been properly documented in scientific literature," said principal author Jerome Dobson, professor emeritus of geography at KU. "We named it the Bering Transitory Archipelago; it existed from about 30,000 years ago through 8,000 years ago. When we saw it, we immediately thought, 'Wow, maybe that's how the first Americans came across.' And, in fact, everything we've tested seems to bear that out -- it does seem to be true."

For more than a decade, researchers have pondered a mystery within a mystery. Mitochondrial DNA indicates that migrants were isolated somewhere for up to 15,000 years on their way over from Asia to North America. The Beringian Standstill Hypothesis arises from the fact that today Native American DNA is quite different from Asian DNA, a clear indication of genetic drift of such magnitude that it can only have happened over long periods of time in nearly complete isolation from the Asian source population. The Bering Transitory Archipelago provides a suitable refugium with internal connectivity and outward isolation.

Dobson said people crossing the Bering Sea probably didn't have sails but could have been experienced in paddling skin boats like the kayaks and umiaks that Inuits use today.

"They probably traveled in small groups," he said, "either from Asia or islands off the coast of Asia. Some maritime people are known to have existed 27,000 years ago on northern Japanese islands. They probably were maritime people -- not just living on islands, but actually practicing maritime culture, economy and travel."

Dobson recently received the American Geographical Society's Cullum Geographical Medal (the same gold medal that Neil Armstrong won for flying to the moon and Rachel Carson won for writing "Silent Spring"). He named and continuously champions "aquaterra" -- all lands that were exposed and inundated repeatedly during the Late Pleistocene ice ages -- thus creating a zone of archeological promise scattered offshore from all coastal regions around the globe.

Recently, Dobson and co-authors Giorgio Spada of the University of Bologna and Gaia Galassi of Urbino University "Carlo Bo" applied an improved Glacial Isostatic Adjustment model to nine global choke points, meaning isthmuses and straits that have funneled transport and trade throughout history. Significant human migrations are known to have occurred across some of them, including "Beringia"-- all portions of the Bering Sea that were exposed before, during and after the Last Glacial Maximum.

"These Italian ocean scientists read my 'Aquaterra' paper and took it upon themselves to refine the boundaries of aquaterra for the whole world at coarse resolution and for Beringia itself at fine resolution," Dobson said. "Later we agreed to join forces and tackle those nine global choke points. At the end of that study, we suddenly spotted these islands in the Bering Sea, and that became our focus. This had an immediate potential because it could be a real game-changer in terms of all sciences understanding how migration worked in the past. We found startling results in certain other choke points and have begun analyzing them as well."

In Beringia, the three investigators contend, this action produced a "conveyor belt" of islands that rose from the sea and fell back again, pushing bands of people eastward. "The first islands to appear were just off the coast of Siberia," the KU researcher said. "Then islands appeared ever eastward. Most likely migrants kept expanding eastward, too, generally to islands within view and an easy paddle away."

By 10,500 years ago, when the Bering Strait itself first appeared, almost all islands in the west had submerged. Only three islands remained, and paddling distances had increased accordingly. Thus, occupants were forced to evacuate, and they faced a clear choice: return to Asia, which they knew to be populated and may even have left due to population pressures and resource constraints, or paddle east to less known territory, perhaps less populated islands with ample resources.

To fully confirm the idea set forth in the new paper, Dobson said researchers from many fields will need to collaborate as one geographer and two ocean scientists have done here.

"We ourselves are at a stage where we definitely need underwater confirmation," he said. "No doubt underwater archaeologists by title will prevail in that quest, but other disciplines, specialties and fields are essential. Working together plus scouring diverse literature, we presented a fundamentally new physical geography for scientists to contemplate. That should entice every relevant discipline to question conventional theory and explore new ideas regarding how, when and where people came to North America. More broadly, aquaterra can serve as a unifying theme for understanding human migrations, demic expansions, evolutionary biology, culture, settlement and endless other topics."

NEW YORK, NY (April 29, 2021)--A new study is drawing the most detailed picture yet of SARS-CoV-2 infection in the lung, revealing mechanisms that result in lethal COVID-19, and may explain long-term complications and show how COVID-19 differs from other infectious diseases.

Led by researchers at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, the study found that in patients who died of the infection, COVID-19 unleashed a detrimental trifecta of runaway inflammation, direct destruction and impaired regeneration of lung cells involved in gas exchange, and accelerated lung scarring.

Though the study looked at lungs from patients who had died of the disease, it provides solid leads as to why survivors of severe COVID may experience long-term respiratory complications due to lung scarring.

"It's a devastating disease, but the picture we're getting of the COVID-19 lung is the first step towards identifying potential targets and therapies that disrupt some of the disease's vicious circuits. In particular, targeting cells responsible for pulmonary fibrosis early on could possibly prevent or ameliorate long-term complications in survivors of severe COVID-19," says Benjamin Izar, MD, PhD, assistant professor of medicine, who led a group of more than 40 investigators to complete in several months a series of analyses that usually takes years.

This study and a companion paper led by researchers at Harvard/MIT, to which the Columbia investigators also contributed, were published the journal Nature on April 29.

Study Creates Atlas of Cells in COVID Lung

The new study is unique from other investigations in that it directly examines lung tissue (rather than sputum or bronchial washes) using single-cell molecular profiling that can identify each cell in a tissue sample and record each cell's activity, resulting in an atlas of cells in COVID lung.

"A normal lung will have many of the same cells we find in COVID, but in different proportions and different activation states," Izar says. "In order to understand how COVID-19 is different compared to both control lungs and other forms of infectious pneumonias, we needed to look at thousands of cells, one by one."

Izar's team examined the lungs of 19 individuals who died of COVID-19 and underwent rapid autopsy (within hours of death)--during which lung and other tissues were collected and immediately frozen--and the lungs of non-COVID-19 patients. In collaboration with investigators at Cornell University, the researchers also compared their findings to lungs of patients with other respiratory illnesses.

Drugs Targeting IL-1beta May Reduce Inflammation

Compared to normal lungs, lungs from the COVID patients were filled with immune cells called macrophages, the study found.

Typically during an infection, these cells chew up pathogens but also regulate the intensity of inflammation, which also helps in the fight.

"In COVID-19, we see expansion and uncontrolled activation of macrophages, including alveolar macrophages and monocyte-derived macrophages," Izar says. "They are completely out of balance and allow inflammation to ramp up unchecked. This results in a vicious cycle where more immune cells come in causing even more inflammation, which ultimately damages the lung tissue."

One inflammatory cytokine in particular, IL-1beta, is produced at a high rate by these macrophages.

"Unlike other cytokines such as IL-6, which appears to be universally prevalent in various pneumonias, IL-1beta production in macrophages is more pronounced in COVID-19 compared to other viral or bacterial lung infections," Izar says. "That's important because drugs exist that tamp down the effects of IL-1beta."

Some of these drugs are already being tested in clinical trials of COVID patients.

Severe COVID also Prevents Lung Repair

In a typical infection, a virus damages lung cells, the immune system clears the pathogen and the debris, and the lung regenerates.

But in COVID, the new study found that not only does SARS-CoV-2 virus destroy alveolar epithelial cells important for gas exchange, the ensuing inflammation also impairs the ability of the remaining cells to regenerate the damaged lung. Though the lung still contains cells that can do the repairs, inflammation permanently traps these cells in an intermediate cell state and leaves them unable to complete the last steps of differentiation needed for replacement of mature lung epithelium.

"Among others, IL-1b appears to be a culprit in inducing and maintaining this intermediate cell state," says Izar, "thereby linking inflammation and impaired lung regeneration in COVID-19. This suggests that in addition to reducing inflammation, targeting IL-1beta may help take the brakes off cells required for lung repair."

Preventing Accelerated Fibrosis

The researchers also found a large number of specific fibroblast cells, called pathological fibroblasts, that create rapid scarring in COVID-19 lungs. When the fibroblast cells fill the lung with scar tissue, a process called fibrosis, the lung has less space for cells involved in gas exchange and is permanently damaged.

Given the importance of pathological fibroblasts in the disease, Izar's team closely analyzed the cells to uncover potential drug targets. An algorithm called VIPER, developed previously by Andrea Califano, Dr, chair of systems biology at Columbia University Vagelos College of Physicians and Surgeons, identified several molecules in the cells that play an important role and could be targeted by existing drugs.

"This analysis predicted that inhibition of STAT signaling could alleviate some of the deleterious effects caused by pathological fibroblasts," Izar says.

"Our hope is that by sharing this analysis and massive data resource, other researchers and drug companies can begin to test and expand on these ideas and find treatments to not only treat critically ill patients, but also reduce complications in people who survive severe COVID-19."

Team Effort by Several Columbia Labs

"Pulling this study together in such a short period of time was only possible with the help of several teams of researchers at Columbia," Izar says.

Critically, in the first few months of the pandemic, Columbia's Department of Pathology & Cell Biology decided to flash-freeze many tissues from deceased COVID patients to preserve the cells' molecular state. Hanina Hibshoosh, MD, director of the department's tissue bank, initiated the collaboration with Izar's lab, which has expertise in conducting single-cell analyses with frozen tissue. Pathologist Anjali Saqi, MD, professor of pathology & cell biology, was also instrumental in procuring and evaluating the samples.

Jianwen Que, MD, PhD, professor of medicine, and his laboratory provided expertise in identifying and characterizing cells in the lung and their regenerative potential. Fibrosis expert Robert Schwabe, MD, associate professor of medicine, was essential in dissecting mechanisms by which COVID-19 propelled lung scarring. "We are incredibly grateful to all the labs contributing to this effort and very fortunate to be at Columbia with all the necessary expertise at hand in one collaborative environment."