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What The Article Says: This JAMA Insights Clinical Update from the CDC's COVID-19 Response Team discusses the association of changes in COVID-19 case rates and death rates with implementation of state-issued mask mandates and allowance of any on-premises restaurant dining.

Authors: Gery P. Guy Jr, Ph.D., M.P.H., of the Centers for Disease Control and Prevention in Atlanta, is the corresponding author.

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

(doi:10.1001/jama.2021.5455)

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

The human body is an incredibly designed machine, and mechanical processes such as those in the lymphatic system play major roles in maintaining healthy tissue and organs.

Donny Hanjaya-Putra is an assistant professor whose work lies at the intersection of engineering and medicine. He studies the lymphatic system -- the part of the immune system that rids the body of toxins and other unwanted materials. He looks at how to restore dysfunctional lymphatic networks, which are associated with a wide range of diseases, including cancer, cardiovascular disease, diabetes, neurological conditions and metabolic syndromes.

Now Hanjaya-Putra and his team -- bioengineering doctoral student Laura Alderfer, along with Elizabeth Russo, a 2019 graduate; Adriana Archilla, a student from Syracuse University; and Brian Coe, class of '19 -- have demonstrated how extracellular matrix stiffness affects lymphatic vessel function.

The team is combining this knowledge with polymer science and mechanical engineering to build new lymphatic cord-like structures, which help restore normal behavior to dysfunctional lymphatic systems and allow the body to fight the disease.

"Cells can sense mechanical stimuli, such as matrix stiffness, and this activates certain genes to promote lymphatic formation," said Hanjaya-Putra. "We used hydrogels made from hyaluronic acid (a natural sugar molecule) to enhance the cell-binding motif with appropriate mechanical stimuli (matrix stiffness) in a 2D model of lymphatic vessels and successfully stimulated new lymphatic vessel formations."

The team has published its findings in The FASEB Journal of the Federation of American Societies for Experimental Biology.

This type of research is only possible, Hanjaya-Putra said, because of advances in imaging and stem cell biology.

"Traditionally, medical students spent hours studying the cardiovascular system, but not as much emphasis was placed on the lymphatic system," said Hanjaya-Putra. "The reason, in large part, was due to the difficulty in visualizing lymphatic vessels, which are transparent.

"Recent advances have allowed us to use specific cell markers to distinguish between blood endothelial cells and lymphatic endothelial cells, so we can now see and study these very important networks in vitro and in vivo."

Hanjaya-Putra and his team are now developing hydrogels that can be implanted under the skin to promote wound healing as well as gels that can be injected into the body at the site of injury.

Alderfer, the lead author on the FASEB article, was awarded a Fulbright U.S. Student Program Grant to study at the University of Helsinki. She will be studying lymphatic vessel formation in vivo in wound and cardiac injury models with Kari Alitalo, a global leader in the research of lymphatic vessels and translational cancer biology.

When we watch a mime seemingly pull rope, climb steps or try to escape that infernal box, we don't struggle to recognize the implied objects -- our minds automatically "see" them, a new study concludes.

To explore how the mind processes the objects mimes seem to interact with, Johns Hopkins University cognitive scientists brought the art of miming into the lab, concluding that invisible, implied surfaces are represented rapidly and automatically. The work appears today in the journal Psychological Science.

"Most of the time, we know which objects are around us because we can just see them directly. But what we explored here was how the mind automatically builds representations of objects that we can't see at all but that we know must be there because of how they are affecting the world," said senior author Chaz Firestone, an assistant professor who directs the university's Perception & Mind Laboratory. "That's basically what mimes do. They can make us feel like we're aware of some object just by seeming to interact with it."

In the experiments, 360 people were tested online. They watched clips where a character (Firestone himself) mimed colliding with a wall and stepping over a box in a way that suggested those objects were there, only invisible. Afterward, a black line appeared in the spot on the screen where the implied surface would have been. This line could be horizontal or vertical, so it either matched or didn't match the orientation of the surface that had just been mimed. Participants had to quickly answer if the line was vertical or horizontal. The team found people responded significantly faster when the line aligned with the mimed wall or box, suggesting that the implied surface was actively represented in the mind - so much so that it affected responses to the real surface participants saw immediately after.

Participants had been told not to pay attention to the miming, but they couldn't help but be influenced by those implied surfaces, said lead author Pat Little, who did the work as an undergraduate at Johns Hopkins, and is now a graduate student at New York University.

"Very quickly people realize that the mime is misleading them, and that there is no actual connection between what the person does and the type of line that appears," Little said. "They think, 'I should ignore this thing because it's getting in my way', but they can't. That's the key. It seems like our minds can't help but represent the surface that the mime is interacting with - even when we don't want to."

The work is partly inspired by a phenomenon in psychology called the Stroop Effect, where the name for one color is written in ink of a different color (e.g., the word "red" is written in blue ink); when a person is given the task of saying the color of the ink (blue), they can't help but read the mismatched text (red), which distracts them and slows them down. In this regard, miming is like reading: Just as you can't help but read the text you see (even when you're supposed to ignore it), you can't help but recognize the object being mimed, even when it's getting in the way of another task.

While it could seem that the findings diminish the work of mimes - since it suggests our brains are going to imagine these objects automatically - the researchers insist mimes still deserve credit.

"This suggests that miming might be different from other kinds of acting," Little said. "If the mime is skilled enough, understanding what's going on doesn't require any effort at all -- you just get it automatically."

The findings could also inform artificial intelligence related to vision.

"If you're trying to build a self-driving car that can see the world and steer around objects, you want to give it all the best tools and tricks," Firestone said. "This study suggests that, if you want a machine's vision to be as sophisticated as ours, it's not enough for it to identify objects that it can see directly -- it also needs the ability to infer the existence of objects that aren't even visible at all."

Space scientists at the University of Bath in the UK have found a new way to probe the internal structure of neutron stars, giving nuclear physicists a novel tool for studying the structures that make up matter at an atomic level.

Neutron stars are dead stars that have been compressed by gravity to the size of small cities. They contain the most extreme matter in the universe, meaning they are the densest objects in existence (for comparison, if Earth were compressed to the density of a neutron star, it would measure just a few hundred meters in diameter, and all humans would fit in a teaspoon). This makes neutron stars unique natural laboratories for nuclear physicists, whose understanding of the force that binds sub-atomic particles is limited to their work on Earth-bound atomic nuclei. Studying how this force behaves under more extreme conditions offers a way to deepen their knowledge.

Step in astrophysicists, who look to distant galaxies to unravel the mysteries of physics.

In a study described in the Monthly Notices of the Royal Astronomical Society, Bath astrophysicists have found that the action of two neutron stars moving ever faster as they spiral towards a violent collision gives a clue to the composition of neutron-star material. From this information, nuclear physicists will be in a stronger position to calculate the forces that determine the structure of all matter.

RESONANCE

It is through the phenomenon of resonance that the Bath team has made its discovery. Resonance occurs when force is applied to an object at its natural frequency, generating a large, often catastrophic, vibrational motion. A well-known example of resonance is found when an opera singer shatters a glass by singing loudly enough at a frequency that matches the oscillation modes of the glass.

When a pair of in-spiralling neutron stars reach a state of resonance, their solid crust - which is thought to be 10-billion times stronger than steel - shatters. This results in the release of a bright burst of gamma-rays (called a Resonant Shattering Flare) that can be seen by satellites. The in-spiralling stars also release gravitational waves that can be detected by instruments on Earth. The Bath researchers found that by measuring both the flare and the gravitational-wave signal, they can calculate the 'symmetry energy' of the neutron star.

Symmetry energy is one of the properties of nuclear matter. It controls the ratio of the sub-atomic particles (protons and neutrons) that make up a nucleus, and how this ratio changes when subjected to the extreme densities found in neutron stars. A reading for symmetry energy would therefore give a strong indication of the makeup of neutron stars, and by extension, the processes by which all protons and neutrons couple, and the forces that determine the structure of all matter.

The researchers stress that measurements obtained by studying the resonance of neutron stars using a combination of gamma-rays and gravitational-waves would be complementary to, rather than a replacement for, the lab experiments of nuclear physicists.

"By studying neutron stars, and the cataclysmic final motions of these massive objects, we're able to understand something about the tiny, tiny nuclei that make up extremely dense matter," said Bath astrophysicist Dr David Tsang. "The enormous difference in scale makes this fascinating."

Astrophysics PhD student Duncan Neill, who led the research, added: "I like that this work looks at the same thing being studied by nuclear physicists. They look at tiny particles and we astrophysicists look at objects and events from many millions of light years away. We are looking at the same thing in a completely different way."

Dr Will Newton, astrophysicist at the Texas A&M University-Commerce and project collaborator, said: "Though the force that binds quarks into neutrons and protons is known, how it actually works when large numbers of neutrons and protons come together is not well understood. The quest to improve this understanding is helped by experimental nuclear physics data, but all the nuclei we probe on Earth have similar numbers of neutrons and protons bound together at roughly the same density.

"In neutron stars, nature provides us with a vastly different environment to explore nuclear physics: matter made mostly of neutrons and spanning a wide range of densities, up to about ten times the density of atomic nuclei. In this paper, we show how we can measure a certain property of this matter - the symmetry energy - from distances of hundreds of millions of light years away. This can shed light on the fundamental workings of nuclei."

Recent research from the University of Vaasa and the University of Jyväskyla shows that speculation and lottery-like behavior is a fundamental factor for the pricing of cryptocurrencies. Speculation could explain the enormous increase in the market capitalizations of cryptocurrencies.

Nowadays more than 8000 cryptocurrencies have been launched. Unlike traditional assets like stocks, research has shown that investments in cryptocurrencies are associated with a considerably higher level of uncertainty. The price of Bitcoin, which is the first traded cryptocurrency, increased by from $7,200.17 to $29,374.15 in January 1, 2020 to January 1, 2021 period corresponding to a return of more than 300 percent in one year.

Interestingly, the sharp increase in the prices for cryptocurrencies happens in a period where the uncertainty in the market for traditional currencies has risen due to the enormous amounts of money that governments worldwide have decided to supply in an attempt to help economies that are on the edge of collapsing due to the ongoing worldwide COVID-19 crisis. The question arises what are the driving forces for pricing cryptocurrencies?

A recently published research article from Klaus Grobys, University of Vaasa and Juha Junttila, University of Jyväskylä in the well-known Journal of International Financial Markets, Institutions and Money explores this current issue.

In their study, the researchers examined the role of speculative behavior in cryptocurrency markets, that is, lottery-like demand. Their study makes use of a set of 20 cryptocurrencies to implement the analysis of the so-called MAX-effect over the January 2016-December 2019 period. These cryptocurrencies exhibited the highest market capitalizations. Their findings indicate that the portfolio of cryptocurrencies that exhibited the lowest daily log-return in the week preceding portfolio formation generates, on average, significantly higher returns than the portfolio of cryptocurrencies that exhibited the highest daily log-return in the week preceding portfolio formation. However, it is important to note that this result is based on portfolio analysis.

The authors also propose a new statistical methodology to compute risk-adjust the payoffs which is based on blocks bootstraps using different block lengths. They show that their new statistical methodology has some benefits because it ensures both (i) latent regimes in the first or second moment in that data generating process are preserved, and (ii) valuable information in the data is not lost.

Moreover, the authors explore the transition probabilities which answers the question of how likely is it that a single cryptocurrency will exhibit an extreme return in the time period that follows the portfolio formation. In this regard, their findings indicate that cryptocurrencies that have experienced extreme positive returns in the past are more likely to generate extreme positive returns in the future than generating extreme negative returns which in turn implies that investors' expectations appear to be rational.

The authors argue that their findings are also interesting from a theoretical point of view because they suggest that similar behavioral mechanisms of underlying investor behavior observed for stock markets are present even in digital financial markets.

- Earlier studies have shown that short-term return reversal and size are priced in the cross section of expected cryptocurrency returns. Another recent stream of research has shown that 50% of Bitcoin turnover is associated with criminal activities. Our study is the first that demonstrates that lottery-like behavior is also an important driving force that plays a role for pricing cryptocurrencies, says Dr. Klaus Grobys.

- Lottery-like behavior might actually explain part of the very recently observed rocket-wise rising valuation of some segments of cryptocurrency markets, too, emphasizes Professor Juha Junttila.

- A good example of this kind of betting behavior is the case of Wallstreetbets forum available from the social media site Reddit. There, the sudden increase in the number of micro level investors investing in some individual stocks has now caused a huge increase in the valuation of these stocks, and the fundamental pricing factors (like the expected future economic performance of the firm in question) have lost their role in the pricing behavior, at least for a short run. In cryptocurrency markets, this kind of behavior has been actually observed, too, so the MAX behavior in cryptocurrency markets can actually be also a reflection of these kinds of activities at the micro investor level. Obviously, our current results deserve much more scrutiny in the near future, says Junttila.

A team of researchers at the University of Alberta has uncovered a long-sought link in the battle to control cholesterol and heart disease.

The protein that interferes with low-density lipoprotein (LDL) receptors that clear "bad" cholesterol from the blood was identified in findings recently published in Nature Communications by Dawei Zhang, associate professor of pediatrics in the Faculty of Medicine & Dentistry. Excess LDL cholesterol can lead to atherosclerosis--a narrowing and hardening of arteries--and ultimately, heart attack.

"We have known for many years that these receptors could be cleaved, but nobody knew which protein was responsible," said Zhang. "There had been several attempts around the world but nobody else was successful."

Now that the culprit has been identified, Zhang's lab is already at work to find a drug to target the protein, allowing the receptors to clear more LDL.

A cholesterol-reducing class of drugs called statins--Lipitor and Crestor are two well-known brand names--has been shown to reduce cardiac events by 20 to 40 per cent, but they have side-effects that mean they can't be given in high enough doses to work for everyone. The new drug would be used in combination with statins to boost their effect, Zhang said.

Zhang's team stumbled upon the role of the protein--membrane type 1 matrix metalloproteinase--by accident while studying another protein involved in heart function. They then set out to repeat and confirm their findings in mouse, rat and human cells, working in collaboration with researchers in China and other faculty members at the U of A. Their study was funded by the Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research. Zhang is also a member of the Women and Children's Health Research Institute.

The protein has other critical physiological functions, Zhang explained, so his lab will work to identify and focus on the specific region within the protein that acts on the LDL receptor. They are also working with a new technique to further target their potential drug so it will work only within the liver, further reducing the likelihood of unwanted side-effects. Their early results are encouraging, Zhang said.

Zhang noted the protein is also critical for cancer tumour invasion, so the team will collaborate with U of A oncology experts to learn more.

"The one protein is a shared risk factor for the two most common diseases in humans--cancer and cardiovascular disease," he said. "We will explore whether we can target one protein to reduce the incidence of the two most common human diseases."

NASA's OSIRIS-REx mission is on the brink of discovering the extent of the mess it made on asteroid Bennu's surface during last fall's sample collection event. On Apr. 7, the OSIRIS-REx spacecraft will get one last close encounter with Bennu as it performs a final flyover to capture images of the asteroid's surface. While performing the flyover, the spacecraft will observe Bennu from a distance of about 2.3 miles (3.7 km) - the closest it's been since the Touch-and-Go Sample Collection event on Oct. 20, 2020.

The OSIRIS-REx team decided to add this last flyover after Bennu's surface was significantly disturbed by the sample collection event. During touchdown, the spacecraft's sampling head sunk 1.6 feet (48.8 centimeters) into the asteroid's surface and simultaneously fired a pressurized charge of nitrogen gas. The spacecraft's thrusters also mobilized a substantial amount of surface material during the back-away burn. Because Bennu's gravity is so weak, these various forces from the spacecraft had a dramatic effect on the sample site - launching many of the region's rocks and a lot of dust in the process. This final flyby of Bennu will provide the mission team an opportunity to learn how the spacecraft's contact with Bennu's surface altered the sample site and the region surrounding it.

The single flyby will mimic one of the observation sequences conducted during the mission's Detailed Survey phase in 2019. OSIRIS-REx will image Bennu for 5.9 hours, which is just over a full rotation period of the asteroid. Within this timeframe, the spacecraft's PolyCam imager will obtain high-resolution images of Bennu's northern and southern hemispheres and its equatorial region. The team will then compare these new images with the previous high-resolution imagery of the asteroid obtained during 2019.

Most of the spacecraft's other science instruments will also collect data during the flyover, including the MapCam imager, the OSIRIS-REx Thermal Emission Spectrometer (OTES), the OSIRIS-REx Visible and Infrared Spectrometer (OVIRS), and the OSIRIS-REx Laser Altimeter (OLA). Exercising these instruments will give the team a chance to assess the current state of each science instrument onboard the spacecraft, as dust coated the instruments during the sample collection event. Understanding the health of the instruments is also part of NASA's evaluation of possible extended mission opportunities after the sample is delivered to Earth.

After the Bennu flyby, it will take several days for the data from the flyover to be downlinked to Earth. Once the data are downlinked, the team will inspect the images to understand how OSIRIS-REx disturbed the asteroid's surface material. At this point, the team will also be able to evaluate the performance of the science instruments.

The spacecraft will remain in asteroid Bennu's vicinity until May 10, when the mission will enter its Return Cruise phase and begin its two-year journey back to Earth. As it approaches Earth, the spacecraft will jettison the Sample Return Capsule (SRC) that contains the rocks and dust collected from Bennu. The SRC will then travel through the Earth's atmosphere and land under parachutes at the Utah Test and Training Range on Sep. 24, 2023.

Once recovered, the capsule will be transported to the curation facility at the agency's Johnson Space Center in Houston, where the sample will be removed for distribution to laboratories worldwide, enabling scientists to study the formation of our solar system and Earth as a habitable planet.

For years, research to pin down the underlying cause of Alzheimer's Disease has been focused on plaque found to be building up in the brain in AD patients. But treatments targeted at breaking down that buildup have been ineffective in restoring cognitive function, suggesting that the buildup may be a side effect of AD and not the cause itself.

A new study led by a team of Brigham Young University researchers finds novel cellular-level support for an alternate theory that is growing in strength: Alzheimer's could actually be a result of metabolic dysfunction in the brain. In other words, there is growing evidence that diet and lifestyle are at the heart of Alzheimer's Disease.

"Alzheimer's Disease is increasingly being referred to as insulin resistance of the brain or Type 3 Diabetes," said senior study author Benjamin Bikman, a professor of physiology and developmental biology at BYU. "Our research shows there is likely a lifestyle origin to the disease, at least to some degree."

For the new study, published in academic journal Alzheimer's & Dementia, the BYU research team examined RNA sequences in 240 post-mortem Alzheimer's Disease-impacted brains. They were looking specifically at the gene expression of nervous system support cells during two types of metabolism: glucose metabolism, where carbohydrates are broken down to provide energy, and something called ketolytic metabolism.

Ketolytic metabolism involves the brain creating energy from ketones, molecules made in our body when the hormone insulin is low and we are burning relatively higher amounts of fat. The popular "Keto Diet" is named after the process since that low-carb, high-protein diet lowers insulin levels and causes the body to burn fat instead of carbs and produce ketones.

The researchers found widespread glucose metabolism impairment in those nervous system support cells of the brains of former Alzheimer's Disease patients, but limited ketolytic metabolism impairment. The finding is significant because the brain is like a hybrid engine, with the ability to get its fuel from glucose or ketones, but in the Alzheimer's brains studied, there appears to be a fundamental genetic deficit in the brain's ability to use glucose.

"We've turned the hybrid engine of our brains into a mono-fuel system that just fails to thrive," Bikman said. "And so, the brain, which is progressively becoming deficient in its ability to use glucose, is now crying out for help; it's starving in the midst of plenty. The body is swimming in a sea of glucose, but the brain just can't use it.

"The inability to use glucose increases the value of ketones. However, because the average person is eating insulin-spiking foods so frequently, there's never any ketones available to the brain," Bikman added. "I look at these findings as a problem we've created and that we're making worse."

Previous research has observed that the brains of people with AD have a quantifiable reduction in the ability to take in and use glucose, but this paper is the first to show it actually happens at the cellular level. It's a significant contribution to the growing paradigm shift in regards to the scientific view of the causes of Alzheimer's.

And since ketolytic metabolism seems to keep working fine in people with AD, even when glucose metabolism gives out, the paper concludes that treatments involving ketones may be able to support brain metabolism and slow the cognitive decline associated with the disease.

Los Angeles (April 1, 2021) -- Overweight children and adolescents receiving chemotherapy for treatment of leukemia are less successful battling the disease compared to their lean peers. Now, research conducted at the Cancer and Blood Disease Institute at Children's Hospital Los Angeles indicates that modest changes in diet and exercise can greatly increase survival in youth treated for acute lymphoblastic leukemia (ALL), the most common childhood cancer.

"To our knowledge, this is the first study to show that by limiting calories and increasing exercise we can make chemotherapy more effective in eliminating leukemia cells within the first month of therapy, decreasing the chances of disease relapse in children and adolescents," says Principal Investigator Etan Orgel, MD, MS, Director of the Medical Supportive Care Service in the Cancer and Blood Disease Institute at Children's Hospital Los Angeles. The study is published in the American Society of Hematology's journal Blood Advances.

Youth who are obese when they begin chemotherapy are more than twice as likely to have remaining cancer cells after one month of treatment--and an increased chance of disease relapse--compared to their lean counterparts. To address this, the investigators worked with registered dietitians and physical therapists who created personalized diet and exercise plans for 40 patients between the ages of 10 and 21 with newly diagnosed leukemia.

The investigators found that patients who reduced their caloric intake by at least 10% and began a modest exercise regimen beginning at diagnosis were, on average, 70% less likely to have remaining leukemia cells in their bone marrow one month after beginning chemotherapy, compared to previously treated patients who did not participate in the diet and exercise intervention. Remaining leukemia cells, called minimal residual disease, is one of the strongest predictors of poor survival outcomes.

"This is proof of concept that it is possible to increase the effectiveness of chemotherapy without adding other medications and their potential side effects," says Dr. Orgel, who is also an associate professor of clinical pediatrics at the Keck School of Medicine of USC. "This short-term intervention is inexpensive and easily available to providers and families everywhere."

The investigators found that by limiting fat, patients also had decreased insulin resistance as well as increased levels of adiponectin, a metabolic hormone associated with glucose regulation. Identification of these potential biomarkers paves the way to using this intervention to impact other types of cancer.

"Changing diet and exercise made the chemotherapy work better-- that's the big news of this study. But we also need to figure out how," says Steven Mittelman, MD, PhD, Chief of Pediatric Endocrinology at UCLA Mattel Children's Hospital and member of UCLA's Jonsson Comprehensive Cancer Center. "Understanding the biological changes responsible for this effect will help us make these interventions even better." Dr. Mittelman co-led the study and was senior author on the paper.

This clinical trial, called Improving Diet and Exercise in ALL (IDEAL-1), builds on basic and preclinical research conducted for more than a decade at Children's Hospital Los Angeles. This "bench-to-bedside and back" approach provides new insights for treating devastating diseases, like cancer. Physicians observe an unmet clinical need in their patients, collaborate with colleagues in the lab and can then deliver an intervention to the clinic to test its effectiveness.

A randomized trial is planned for later this year. Called IDEAL-2, the study will be conducted by Dr. Orgel and Dr. Mittelman through the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium, headquartered at Children's Hospital Los Angeles under the medical leadership of Alan Wayne, MD, and Deepa Bhojwani, MD.

SEATTLE (April 1, 2021) - An international consortium of geneticists, biologists, clinicians, mathematicians, and other scientists is determined to take the study of the human genome to the next level - creating a comprehensive atlas of genetic variants to advance the understanding, diagnosis, and treatment of disease.

"This Herculean undertaking is unprecedented," said Dr. Matthew Hurles, a geneticist at the Wellcome Sanger Institute in Cambridge, England. "Indeed, the scientific community has an increasingly comprehensive catalog of functional DNA elements in the human genome, but that catalog remains incomplete. We have collectively characterized the functional impact of less than 1% of genetic variation in the 1 to 2 percent of our DNA."

Hurles and Dr. Doug Fowler, a member of the Brotman Baty Institute for Precision Medicine (BBI) and professor of Genome Sciences at the University of Washington's UW Medicine, want to increase those percentages significantly.

They are founding members of the Atlas of Variant Effects (AVE) Alliance and co-authors of a white paper outlining what may be the most ambitious task over the past 30 years since the Human Genome Project.

AVE, along with BBI and the Center for the Multiplexed Assessment of Phenotype, is co-hosting the fourth annual "Mutational Scanning Symposium." The event will bring together global experts performing leading edge research in precision medicine, functional genomics, protein science, and variant interpretation and prediction and will be held virtually for three days beginning on Monday, April 5. Those interested in participating in the free symposium may learn more at https://www.varianteffect.org/aveevents/mutational-scanning-symposium.

The launch of the AVE alliance and the consortium's effort to create the atlas of human genome variants are key issues to be covered at the meeting. The atlas will also examine technology development, data generation, data analysis, data coordination and sharing, and clinical and biological translation.

"We've never known so much about naturally occurring variation in the human genome and now is the time to seize the opportunity to understand what that variation means for human health," said Anna L. Gloyn, DPhil, professor of pediatrics at the Stanford University School of Medicine and an AVE Executive Committee member.

The initial efforts of members of the AVE Alliance will focus on quantifying the functional impact of single nucleotide variants at the genomic loci, primarily human protein-coding genes, that offer the greatest and most immediate clinical utility.

"The ultimate goal is to develop a systematic, extensive understanding of the functional impact of variants in human, model organism and pathogen genomes," Fowler said.

"However, the field of variant effect mapping is already yielding major impacts. We believe and expect that a coordinated and phased approach with others globally could be transformative. The first major, 'real world' impact of the atlas of variant effects is expected to be improved genetic diagnosis and precision medicine."

East Hanover, NJ. April 1, 2021. A team of New Jersey researchers has shown that changes in perceptual certainty and response bias, two central metrics of signal detection theory (SDT), correlate with changes in cognitive fatigue. They also show that SDT measures change as a function of changes in brain activation. This finding was reported in Frontiers in Psychology on January 15, 2021, in the open access article "Using Signal Detection Theory to Better Understand Cognitive Fatigue" (doi:10.3389/fpsyg.2020.579188).

The authors are Glenn Wylie, DPhil, Brian Yao, PhD, and John DeLuca, PhD, of Kessler Foundation, and Joshua Sandry, PhD, of Montclair State University.

Cognitive fatigue is a common experience that affects the healthy population as well as individuals with brain injury or neurodegenerative disease. A large body of research shows that subjective feelings of cognitive fatigue do not correlate with performance--that is, a person may experience cognitive fatigue and yet objective measures of their performance, such as their response time or level of accuracy, do not necessarily worsen. As a result, researchers have long lacked an objective behavioral measure that covaries with the subjective experience of fatigue.

While previous research has indicated that one metric of SDT, perceptual certainty, may change as a function of fatigue, it remains unclear whether perceptual certainty covaries with fatigue. Moreover, there has been no research investigating the effect of fatigue on the second key SDT metric, response bias, which is the amount of evidence one requires before releasing a response. Understanding if and how cognitive fatigue covaries with both SDT metrics is essential to the development of effective interventions for people with this condition.

The study was conducted at the Rocco Ortenzio Neuroimaging Center at Kessler Foundation, a specialized facility dedicated solely to rehabilitation research. To investigate cognitive fatigue using SDT, the investigators induced cognitive fatigue in 39 healthy volunteers while acquiring both structural and functional magnetic resonance imaging (fMRI) data. They assessed subjects' cognitive fatigue using a visual analogue scale of fatigue (VAS-F) at baseline and after each of the eight runs of the tasks. This enabled the team to assess whether perceptual certainty and response bias covary with cognitive fatigue, and whether similar patterns of brain activation underlie cognitive fatigue and SDT measures.

Researchers found that both SDT metrics were correlated with changes in cognitive fatigue. As fatigue increased, subjects became more conservative in their response bias and their perceptual certainty declined. This study is the first to show that changes in cognitive fatigue are correlated with changes in perceptual certainty.

Furthermore, the research team found that activation in the striatum of the basal ganglia--an area of the brain Kessler researchers have previously identified as sensitive to changes in cognitive fatigue--was also related to response bias and perceptual certainty.

"Our results show that cognitive fatigue is related to changes in subjects' response bias and perceptual certainty," said lead author Dr. Wylie, director of the Ortenzio Center. "We theorize that as cognitive fatigue increases, subjects make more errors because their perceptual sensitivity declines and they compensate for this by adopting a more conservative response bias," he emphasized. "Our work demonstrates the relevance of SDT measures in the understanding of fatigue and provides researchers with a new set of tools with which to better understand the nature and consequences of cognitive fatigue."

Key Takeaways:

Discounting or couponing is not the most effective way to tap the power of retargeting in online marketing.

Customized seller recommendations may be more powerful than discounting.

Seller auctions that allow marketers to self-select in the retargeting process improve cost efficiency.

CATONSVILLE, MD, April 1, 2021 - Online marketers have seen the pattern: 95%-98% of online visitors search for something, but the search never converts into a purchase and they leave the site without buying. For marketers, this results in speculation and assumptions that can lead to wasted time and investments in ineffective marketing programs.

One of the more common ways online marketers attempt to solve this problem is to "retarget," which tracks those consumers and reconnects with them at a later point by showing display ads when they browse other websites. You've probably noticed this when using Google Search to find something, such as a pair of shoes, and then later when you're reading a separate news site, you're exposed to a number of display ads centered on that very thing you were searching for earlier.

Once that marketer gets your attention, what can they do to increase the likelihood that you will make a purchase? That question is at the center of a new study that reveals what the best approach to increase conversion rates may be.

The research study to be published in the April issue of the INFORMS journal Marketing Science, "Consumer Search and Purchase: An Empirical Investigation of Retargeting Based on Consumer Online Behaviors," is authored by Zhenling Jiang of The Wharton School at the University of Pennsylvania; Tat Chan of Washington University in St. Louis; Hai Che of the University of California; and Youwei Wang of Fudan University in Shanghai.

To conduct their research, the authors analyzed consumer behaviors in response to two distinct marketing strategies. In one approach, they sent out coupons via those retargeted display ads to be redeemed upon purchasing. In the other approach, the authors used the same display ads to provide seller recommendations that centered on a specific product offering customized to the user, but with no coupon or discount.

"We found that while both strategies help increase the conversion rate, the seller recommendations were more effective than coupons," said Jiang. "This told us that providing consumers with the sellers' information that is most relevant to them may be a more effective way to tap the power of retargeting."

To conduct their research, the authors tapped empirical data from Taobao.com, which is owned by Alibaba, and is the largest online retail platform in China. Like other major e-commerce platforms, it collects consumer browsing history and can reach consumers through direct messaging on the platform, either through the website or its mobile app. The researchers built a consumer search model to establish the relationship between consumer preference and search behaviors. They studied the behavior of 104,189 consumers who searched for a specific product among 20 sellers.

"We noticed some predictable patterns," said Jiang. "Consumers who had a higher search intensity for a specific product were more likely to actually make a purchase. Search intensity was measured in the volume of clicks tied to the same search or search term. What we found was that even where the consumer clicked on multiple possible products, it was the first link they clicked on that had the highest potential of generating a sale. In other words, after a more intense search, the consumer is more likely to go back to that initial seller once a decision to make a purchase is made."

In addition to the two basic retargeting strategies - discounting or customization - the authors proposed to use auction as a pricing mechanism to implement the policies. The auction pricing mechanism requires the seller to self-select. This means the seller selects certain criteria for its ideal customer for a specific product at a specific price point, and then bids on how much it will pay to reach that consumer.

"Through our research, we were also able to show that a pricing mechanism, such as an auction, also tends to improve the effectiveness of a retargeting program," said Jiang. "When Taobao used a pricing mechanism such as an auction, the company was able to improve the efficiency of its retargeting campaigns."

Below please find a summary of a new article that is published in Annals of Internal Medicine today. The summary is not intended to substitute for the full article as a source of information.

Physicians must advocate for common sense gun laws for good of public health
#thisisourlane
FREE content: https://www.acpjournals.org/doi/10.7326/M21-1505

A pointed editorial by Douglas DeLong, MD, Chief of the Division of General Internal Medicine at Bassett Healthcare in Cooperstown, NY, suggests that it's time for physicians to move past talking and start taking action to protect patients from gun violence and unintentional injury. Dr. DeLong says that in addition to educating patients and their families about firearm safety, physicians must also act locally to stand up against the NRA and advocate for common sense gun laws.

While mass shootings were down overall in 2020, any cause for celebration was short-lived. In March 2021, the U.S. experienced 2 mass shootings taking a total of 18 lives within the span of less than 1 week. The first shooting targeted women and Asian Americans. The motive for the second shooting is not yet known, but the usual "blah, blah, blah" of "thoughts and prayers" was the predictable response from both sides of the political divide.

Dr. DeLong says that now is the time to educate, advocate, and legislate. This means that physicians, given their respected role in society and obligation to promote individual and public health, need to both command their place in the lane (#thisisourlane) and to be at the head of the line with respect to efforts to reduce firearm injury. Dr. DeLong suggests writing letters to editors of local newspapers and to local politicians advocating sensible firearm policy. Physicians can also work with professional societies, such as the American College of Physicians (ACP), which has published several policy papers, position papers, and recommendations on firearm safety, to lobby at all levels for sane firearm injury prevention laws.

Fewer than half of inmates in jails and prisons surveyed in a study by the CDC and University of Washington said they would accept a COVID-19 vaccine, while the majority either said they wanted to wait before getting the vaccine or would refuse one.

"This is a population already at risk for COVID-19, and outbreaks among incarcerated people can worsen inequities in COVID-19 outcomes as well as contribute to spread in the surrounding community," said lead author Dr. Marc Stern, affiliate assistant professor of health services in the UW School of Public Health. "So culturally and health-literacy informed interventions are needed to help them feel more confident about getting vaccinated."

The study conducted by CDC researchers and led by Stern was published Wednesday on the CDC's Morbidity and Mortality Weekly Report. The researchers surveyed more than 5,000 inmates, men and women, in late 2020 from three prisons and 13 jails in Washington, California, Florida and Texas.

Among those asked about their willingness to receive a vaccine, only 45% said they were willing. More than 45% said they would refuse, and nearly 10% said they might or weren't sure they would receive it.

The most common reasons the participants gave for vaccine hesitancy fell into the response categories of waiting for more information or to see others take it first, and efficacy or safety concerns. The most common reason for given for refusal was distrust of the health care system, correctional or government personnel and institutions.

The survey was conducted before vaccines were available, but at the time Black and younger respondents were the least willing to get the vaccine. The researchers added that a lower willingness to receive a vaccine among Black participants was "not unexpected given historical mistreatment and higher rates of distrust" of these institutions.

"People of color are subject to a 'double whammy' -- they are at higher risk of serious illness from COVID-19 and they are disproportionately incarcerated, living in facilities where they are more likely to become infected," Stern said.

"I hope this study sheds light on the need to find ways of assuring high levels of vaccination of incarcerated individuals," Stern added, "not just for their own health, but for the health of the community. Vaccinating incarcerated individuals not only decreases the risk that officers and other staff will bring COVID-19 home to their family, friends and community, it is also an efficient way to vaccinate a large number of people who are otherwise hard for public health providers to reach once they return to their communities."

ROCHESTER, Minn. -- All too often, patients with high levels of antibodies face major challenges getting a transplant. These highly sensitized patients have a much higher risk of death while waiting for suitable organs they are less likely to reject. But there is new hope for highly sensitized patients in need of a combined heart and liver transplant, thanks to an innovative surgical approach at Mayo Clinic.

Traditionally, surgeons transplant the heart first, followed by the liver. But Mayo Clinic heart transplant team decided to reverse the order for highly sensitized patients in the hopes that the liver would absorb some of the patient's antibodies, removing them from circulation and lowering the risk of antibody-mediated rejection. The strategy worked, according to a study recently published in the Journal of the American College of Cardiology.

"This unique approach to heart-liver transplant opens the door to more highly sensitized patients getting the transplants they desperately need," says Sudhir Kushwaha, M.D., a Mayo Clinic cardiologist and the study's senior author.

More than 107,000 people in the U.S. are on the waitlist for a lifesaving transplant, according to the Organ Procurement and Transplantation Network. An estimated 20% of people waiting for a transplant are highly sensitized, meaning they have high antibody levels that can cause the immune system to reject a transplanted organ. People can become sensitized due to blood transfusions, pregnancies and previous transplants. April is National Donate Life Month, which encourages people to register to be organ, eye and tissue donors, and honor those who have given the gift of life.

The Mayo Clinic team was inspired to try the heart-after-liver transplant procedure after noting that patients who had undergone a traditional heart-liver transplant were much less likely to experience rejection than those who had a heart transplant alone. Previous research has shown a similar phenomenon for patients undergoing a simultaneous kidney-liver transplant.

Mayo Clinic began offering the pioneering heart-after-liver transplant surgery in 2011. The recently published study reviews the outcomes for seven patients who underwent the procedure. The patients were ages 33-51, and six of the seven were women. All experienced a significant drop in antibodies after the procedure was performed, and none of the patients had experienced rejection within four years following surgery. The study's limitations include its small sample size and younger age of typical transplant patients.

While this new procedure is promising, it comes with major challenges. The heart is usually transplanted first because it is more time-sensitive than other organs. The reverse-order procedure requires a complex choreography between the heart and liver transplant teams to accomplish the procedure.

"Timing is everything. These surgeries require the heart and liver transplant teams to work closely together to limit the time it takes to transplant the donated organs," says Richard Daly, M.D., a Mayo Clinic cardiothoracic surgeon and the paper's first author.