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Currently, there are over 10 million confirmed cases and more than 240,000 casualties attributed to COVID-19 in the U.S. Researchers at Louisiana State University have applied computational models to investigate infection rates in relation to social distancing measures. Their paper, Effect of mitigation measures on the spreading of COVID-19 in hard-hit states in the U.S., was recently published in PLOS ONE.

This research compiles the data for each state in the U.S. and calculates the change in the infection rate before and after social distance measures were imposed last spring.

"We investigate the change in the infection rate due to mitigation efforts and project death and infection counts through September 2020 for some of the most heavily impacted states: New York, New Jersey, Michigan, Massachusetts, Illinois, and Louisiana," said co-author Juana Moreno, LSU Department of Physics & Astronomy and the Center for Computation & Technology associate professor.

Many of the current predictive models of the development of COVID-19, especially after mitigation efforts, partially rely on extrapolations from data collected in other countries. However, understanding the effects of mitigation efforts based on local data is important, since data extrapolated from other areas may not be reliable. As states and countries have implemented different degrees of social distancing measures, the effects on controlling the pandemic simply cannot be translated between regions.

"The interactions among people are complicated and often difficult to model at the individual level. The challenge is similar to the study of a large ensemble of particles where monitoring the motion of each particle is virtually impossible. Mean field approximation is often used to study large populations by coarse graining the individual, or microscopic, details to the population, or macroscopic, averaged quantity," said lead author Ka-Ming Tam, LSU Department of Physics & Astronomy research assistant professor.

With the current mitigation efforts, five of those six states with the exception of Illinois, have reduced their base reproduction number to a value less than one, stopping the exponential growth of the pandemic.

"The infection rate is an important indicator of the evolution of an epidemic. If it is larger than one, the number of infections is exponentially increasing," said Nicholas Walker, LSU Department of Physics & Astronomy alumnus and current postdoctoral fellow. "We found that the infection rate is substantially suppressed by social distancing measures. Almost all states had the infection rate dropped below one by the end of the April."

The analyses by the researchers clearly shows a drop in infection rates following public policy measures such as social distancing and stay-at-home orders.

"We are currently working on the effects of reopening and how the reopening policies in different states have affected the number of fatalities," Moreno said. "Our current analysis suggests that the face mask mandate is the most important policy for lowering the death count."

Metabolic robustness, the ability of a metabolic system to buffer changes in its environment, is not always a welcome feature for microbiologists: it interferes with metabolic engineering or prevents that antibiotics kill bacteria. Therefore it is important to understand the mechanisms that enable metabolic robustness. A massively parallel CRISPRi screen demonstrated that E. coli metabolism is very robust against knockdowns of enzymes, and multi-omics data revealed the mechanisms behind it. In the future, the researchers want to apply this knowledge to build better models of metabolism, which enable rational-design of industrial microbes.

In their natural habitat, bacteria like E. coli are confronted with constant changes in the composition of nutrients. But under laboratory conditions, they can also be real specialists, and grow for instance on a single carbon source like glucose. To do so, their metabolic network must synthesize all cellular building blocks from scratch. This task requires that hundreds of enzyme-catalyzed reaction in the metabolic network work at the right pace, and that no reaction accidently falls below a critical threshold. Otherwise, a single bottleneck in the network may have wide-spread consequences and eventually stop cellular growth.

To understand how E. coli accomplishes this task, researchers led by Dr. Hannes from the Max Planck Institute for terrestrial Microbiology applied the CRISPR interference (CRISPRi) technology. By inducing knockdowns of each protein in the metabolic network of E. coli, they created a CRISPRi library with 7177 strains. Deep sequencing of the library during a pooled competition assay allowed the researchers to track fitness of each CRISPRi strain for 14 hours. The results of this massively parallel CRISPR screen were somewhat surprising. While knockdowns of only seven genes - keypoints in the metabolic network, like biosynthesis of deoxynucleotides for DNA synthesis - caused immediate and strong fitness defects, hundreds of other knockdowns had little effects.

As Dr. Hannes Link explains: "Our results demonstrated that E. coli cells accomplish a very high metabolic robustness. In general, robustness enables living organisms to survive despite external and internal disturbances, and there are different mechanisms that mediate it, such as feedback mechanisms or redundancy. In this context, organisms are always in a trade-off situation: either they express high enzyme concentrations, which is costly; or the express low enzyme concentrations which can limit the metabolic capacity. For us researchers, robustness is not always a welcome feature in bacteria, for example in the course of biotechnological applications, if we want to engineer metabolism to overproduce chemicals with bacteria. Therefore it is important to understand how E. coli accomplishes this task."

To answer this question, the team measured the proteome and metabolome of 30 CRISPRi strains. In some strains the proteome responses revealed mechanisms that actively buffered the CRISPRi knockdowns. For example, knockdown of homocysteine transmethylase (MetE) in the methionine pathway caused a compensatory upregulation of all other enzymes in the methionine pathway. In other words, E. coli cells sensed that the knockdown caused a bottleneck in methionine biosynthesis and then mounted a very precise and local response around the methionine pathway. The other 30 CRISPRi strains revealed similar buffering mechanisms that were surprisingly specific, but whether all metabolic pathways are equipped with such precise and localized buffering mechanisms remains open. Therefore, the Link Lab is currently innovating new mass spectrometry methods to probe the complete metabolism of the complete CRISPRi library.

This comprehensive approach creates new possibilities for the development of industrially useful microbes, as Dr. Hannes Link points out: "In the future, we want to use these data to construct metabolic models that are dynamic and predictive. We used a very small dynamic model in the current study, but building larger models remains one of the big challenges. Such models would allow us to engineer E. coli cells that stop growing upon a certain signal and then concentrate all metabolic resources on the synthesis of a desired chemical. This controlled decoupling of growth from overproduction would break new ground in metabolic engineering and opens new applications in industrial biotechnology."

Reduced food intake, known as dietary restriction, leads to a longer lifespan in many animals and can improve health in humans. However, the molecular mechanisms underlying the positive effects of dietary restriction are still unclear. Researchers from the Max Planck Institute for Biology of Ageing have now found one possible explanation in fruit flies: they identified a protein named Sestrin that mediates the beneficial effects of dietary restriction. By increasing the amount of Sestrin in flies, researchers were able to extend their lifespan and at the same time these flies were protected against the lifespan-shortening effects of a protein-rich diet. The researchers could further show that Sestrin plays a key role in stem cells in the fly gut thereby improving the health of the fly.

The health benefits of dietary restriction have long been known. Recently, it has become clear that restriction of certain food components, especially proteins and their individual building blocks, the amino acids, is more important for the organism's response to dietary restriction than general calorie reduction. On the molecular level, one particular well-known signalling pathway, named TOR pathway, is important for longevity.

"We wanted to know which factor is responsible for measuring nutrients in the cell, especially amino acids, and how this factor affects the TOR pathway", explains Jiongming Lu, researcher in the department of Linda Partridge at the Max Planck Institute for Biology of Ageing. "We focused on a protein called Sestrin, which was suggested to sense amino acids. However, no one has ever demonstrated amino acid sensing function of Sestrin in a living being." Therefore, Lu and his colleagues focused on the role of Sestrin in the model organism Drosophila melanogaster, commonly known as fruit fly.

Sestrin as a potential anti-ageing factor

"Our results in flies revealed Sestrin as a novel potential anti-ageing factor", says Linda Partridge, head of the research team. "We could show that the Sestrin protein binds certain amino acids. When we inhibited this binding, the TOR signalling pathway in the flies was less active and the flies lived longer", adds Lu. "Flies with a mutated Sestrin protein unable to bind amino acids showed improved health in the presence of a protein-rich diet."

Particularly interesting: If the researchers increased the amount of Sestrin protein in stem cells located in the fly gut, these flies lived about ten percent longer than control flies. In addition, the increased Sestrin amounts only in the gut stem cells also protected against the negative effect of a protein-rich diet. Lu continues: "We are curious whether the function of Sestrin in humans is similar as in flies. Experiments with mice already showed that Sestrin is required for the beneficial effects of exercise on the health of the animal. A drug that increases the activity of the Sestrin protein might therefore be in future a novel approach to slow down the ageing process."

WOODS HOLE, Mass. — When you think of swimming, you probably imagine pushing through the water—creating backwards thrust that pushes you forward. New research at the Marine Biological Laboratory (MBL) suggests instead that many marine animals actually pull themselves through the water, a phenomenon dubbed “suction thrust.”

The study, published in Scientific Reports, found that small marine animals with multiple propulsers—including larval crabs, polychaete worms, and some types of jellyfish—don’t push themselves forward when they move their appendages, but instead create negative pressure behind them that pulls them through the water.

When the front appendage moves, it creates a pocket of low pressure behind it that may reduce the energy required by the next limb to move. “It is similar to how cyclists use draft to reduce wind drag and to help pull the group along,” says lead author Sean Colin of Roger Williams University, a Whitman Center Scientist at the MBL.

This publication builds on the team’s previous work, also conducted at the MBL, on suction thrust in lampreys and jellyfish. For the current study, they focused on small marine animals that use metachronal kinematics also known as “metachronal swimming,” a locomotion technique commonly used by animals with multiple pairs of legs in which appendages stroke in sequence, rather than synchronously.

“We came into this study looking for the benefits of metachronal swimming, but we realized the flow around the limbs looks very similar to the flow around a jellyfish or a fish fin,” said Colin. “Not only does the flow look the same, but the negative pressure is the same.”

For this study, the researchers worked with two crab species, a polychaete worm, and four species of comb jellies. All are smaller than a few millimeters in length. They found that the fluid flow created while swimming was the same as in the larger animals they had previously studied.

“Even at these really small scales, these animals rely on negative pressure to pull themselves forward through the water,” said Colin, who added that this could be a common phenomenon among animals.

“It’s not unique to the fish or the jellyfish we looked at. It’s probably much more widespread in the animal kingdom,” says Colin, who added that something like suction thrust has been observed in birds and bats moving themselves through the air. These creatures have the same degree of bend in their limbs (25-30 degrees) that the observed marine animals do.

Moving forward, Colin and colleagues want to study a larger variety of marine organisms to determine the range of animal sizes that rely on suction thrust to propel through the water.

“That’s one of our main goals — to get bigger, get smaller, and get a better survey of what animals are really relying on this suction thrust,” Colin says.

Palo Alto, CA-- Anthraquinones are a class of naturally occurring compounds prized for their medicinal properties, as well as for other applications, including ecologically friendly dyes. Despite wide interest, the mechanism by which plants produce them has remained shrouded in mystery until now.

New work from an international team of scientists including Carnegie's Sue Rhee reveals a gene responsible for anthraquinone synthesis in plants. Their findings could help scientists cultivate a plant-based mechanism for harvesting these useful compounds in bulk quantities.

"Senna tora is a legume with anthraquinone-based medicinal properties that have long been recognized in ancient Chinese and Ayurvedic traditions, including antimicrobial and antiparasitic benefits, as well as diabetes and neurodegenerative disease prevention," Rhee explained.

Despite its extensive practical applications, genomic studies of Senna have been limited. So, led by Sang-Ho Kang of the Korean National Institute of Agricultural Sciences and Ramesh Prasad Pandey of Sun Moon University and MIT, the research team used an array of sophisticated genetic and biochemical approaches to identify the first known anthranoid-forming enzyme in plants.

"Now that we've established the first step of the ladder, we can move quickly to elucidate the full suite of genes involved in the synthesis of anthraquinone," said lead author Kang.

Once the process by which plants make these important compounds is fully known, this knowledge can be used to engineer a plant to produce high concentrations of anthraquinones that can be used medicinally.

"The same techniques that we use to help improve the yields of agricultural or biofuel crops can also be applied to developing sustainable production methods for plant-based medicines," Rhee concluded.

November 24, 2020 - In mid-March, public health officials across the San Francisco area issued the first U.S. regional shelter-in-place order in response to the emerging COVID-19 pandemic. A "field report" on the crisis decision-making approach followed in that effective early response is featured in a special COVID-19 supplement to the Journal of Public Health Management and Practice. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"With the benefit of hindsight and reflection, we recount our story through the lens of public health legal authority, meta-leadership, and decision intelligence," according to the new article, authored by Tomás J. Aragón, MD, DrPH, of the San Francisco Department of Public Health along with local health officers (LHOs) from six other Bay Area jurisdictions. Their paper appears as part of a JPHMP supplement titled "COVID-19 and Public Health: Looking Back, Moving Forward."

On March 15, 2020, LHOs in Alameda, Contra Costa, Marin, San Francisco, San Mateo, and Santa Clara Counties and the City of Berkeley issued legal orders for 6.7 million residents to shelter-in-place to prevent the spread of SARS-CoV-2. Within days, other regions issued similar orders. Studies have confirmed that early shelter-in-place orders prevented many COVID-19 cases, hospitalizations, and deaths across the United States.

But even in a crisis, outcomes can't determine whether a decision was good or bad. "The quality of a decision depends only on the quality of the decision-making process at the time the decision was made," Dr. Aragón and coauthors write. They review key elements of good crisis decision making during complex public health emergencies:

Crisis Decision Making. Public health decision makers bring epidemiologic (causal and probabilistic) reasoning and the ability to balance tradeoffs from competing objectives to tackle a health crisis. In the face of "volatility, uncertainty, complexity, and ambiguity," team deliberations must be built on trust-based, collaborative relationships and approached with "genuine intellectual humility ... embrac[ing] curiosity over certainty."

Legal Authority. In California, LHOs are authorized to take measures as necessary to control the spread of communicable diseases. This enabled the Bay Area LHOs to act "quickly and decisively" to issue shelter-in-place orders to protect the public health and healthcare system from a COVID-19 surge like that occurring at the time in New York City.

Meta-Leadership. Longstanding state and regional health official networks have played an important role in responding, adapting, and scaling to public health threats. In the Bay Area, years of experience in preparing for pandemic influenza, and responding to other microbial threats, enabled the spontaneous activation of "swarm leadership"--a key characteristic of good disaster responses where a group, without formal hierarchical authority, coalesces to tackle effectively a complex emergency.

Decision Intelligence. Dr. Aragón and colleagues define decision intelligence as "the integration of problem-solving and decision quality within a performance improvement framework, ensuring quality and continuous improvement in crisis decision making." While recognizing that a shelter-in-place order was a "drastic measure," the LHOs agreed that immediate action would maximize the benefits of interrupting transmission: "flattening the curve" of COVID-19 cases, hospitalizations, and deaths while providing time to ensure public health systems readiness and to learn about SARS-CoV-2 biology and transmission.

The Bay Area LHOs hope their experience will draw attention to the elements of crisis decision making - throughout the pandemic and in preparing for future public health emergencies. "Decision intelligence provides practical tools to improve crisis decision making," Dr. Aragon and coauthors conclude. "We hope that with experimentation and practice, public health officials will improve their routine team decisions, and thereby be capable and ready to make better decisions in new crisis situations."

When you take a time-release drug, you count on it doing what the package says: release the drug slowly into your bloodstream to provide benefits over the specified period of time. When the drug dissolves too slowly or too quickly, the results can range from inconvenient-- a decongestant that lets your sinuses get stuffed up too soon-- to tragic, as many who were prescribed OxyContin discovered.

OxyContin, which contains the opiate oxycodone, was supposed to offer 12-hour pain relief. Instead, in some patients it dissolved much more quickly, causing them to take it more frequently and ultimately become addicted.

But assessing how a drug dissolves in the body is surprisingly tricky. Drug dissolution has to be measured under laboratory conditions that come as close as possible to mimicking what happens in the body.

In a paper published in Scientific Reports, UC Riverside researchers describe a simple, inexpensive way to measure drug dissolution that should help pharmaceutical companies develop better and more consistent time-release drug products.

"We directly measured dissolution profiles of single drug granules, which are the little spheres you see when you open up a capsule," said corresponding author William Grover, an associate professor of bioengineering at the Marlan and Rosemary Bourns College of Engineering. "We accomplished this using a vibrating tube sensor, which is just a piece of glass tubing bent in the shape of a tuning fork."

Many factors affect drug dissolution in the body, including the pH and chemical composition of the gastrointestinal fluid, the hydrodynamics of the fluid caused by gastrointestinal contractions, the patient's sex, and metabolism. For example, the makers of OxyContin note taking the drug with a high-fat meal can increase the amount of oxycodone in the patient's blood by 25%.

Pharmaceutical companies usually test drugs by placing them in a vessel filled with fluid that mimics the contents of the gastrointestinal, or GI, tract, and stir the fluid to recreate GI tract dynamics. Small samples of the fluid are taken at intervals and the concentration of the drug, which should be increasing over time, measured using ultraviolet-visible spectroscopy or high-performance liquid chromatography. The data from this testing is used to construct a model of how the drug is expected to behave in the body.

The common ways of testing all have drawbacks. Small differences in the placement of tablets in a vessel can double the measured dissolution rate in one method, for example. Other methods can experience clogged equipment, impeded flow, and air bubbles, all of which affect how the drug dissolves. Moreover, the measurement process is time-consuming, laborious, often irreproducible, and involves expensive equipment. The existing methods also offer only "snapshots" of dissolution, taken at sampling points, providing limited information.

Grover, doctoral student Heran Bhakta, and undergraduate student Jessica Lin took a radically different approach. Rather than measure the increasing concentration of the drug in the fluid, they decided to measure the decreasing mass of a solid pellet as it dissolves.

The group used a glass tube bent like a tuning fork, kept vibrating by a circuit at its resonance frequency, which was determined by the mass of the tube and its contents. When they filled the tube with simulated stomach and intestine contents and passed an over-the-counter time-release drug granule through the tube, they observed a brief change in the frequency.

When plotted, they could compare the peaks of resonance frequency against the time to learn the buoyant mass of the drug granule at that moment.

"By passing the granule back-and-forth through the vibrating tube while it dissolves, we can monitor its weight throughout the dissolution process and obtain single-granule dissolution profiles," Grover said.

The group tested three different controlled-release proton pump inhibitor drugs: omeprazole, lansoprazole, and esomeprazole. Though they all have the same intended function in the body, they have very different granule sizes and dissolution mechanisms.

"We also found different dissolution behaviors between name-brand and generic formulations of the same drug. These differences in single-particle dissolution behavior could lead to different rates of drug absorption in patients," Grover said.

The researchers write that the technique addresses many of the shortcomings of existing testing methods, requires no additional analytical instruments, and is suitable for both fast-dissolving and slow-dissolving formulations. By giving dissolution profiles for individual pellets the method can capture variations in pellet dissolution behavior that other methods can't.

"Our technique is much cheaper and easier to perform than conventional methods, and that enables pharmaceutical companies to do more tests in a wider variety of conditions," said Grover. "We can also easily see differences in dissolution between individual particles in a drug. That should help pharmaceutical companies improve and monitor the consistency of their manufacturing processes."

The technique measures not just active ingredients, but also the inert ingredients in each drug particle.

"That's helpful for manufacturers who want to study how each layer of a controlled-release granule behaves during dissolution," said Bhakta.

The authors hope this data can augment existing dissolution methods and help pharmaceutical developers and manufacturers create better controlled-release drugs.

In a paper published in the journal of Ocular Immunology and Inflammation, physicians from the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine reported that several patients using germicidal lamps in an attempt to sanitize against the coronavirus, developed painful inflammation of the cornea, a condition called photokeratitis. These consumer-available ultraviolet (UV) emitting devices were being used in an attempt to eliminate coronavirus from homes and offices.

"During the height of the pandemic, we noticed an increased number of patients coming in with irritation, pain and sensitivity to light," said first author and Bascom Palmer resident Jesse Sengillo, M.D. "We realized this was after direct exposure to germicidal lamps that emit UV light in the C range to kill bacteria and viruses. This can be quite a painful experience for the patient, but with prompt topical lubrication and antibiotics to prevent infection, patients often do very well."

UV photokeratitis occurs when the cornea is overexposed to ultraviolet radiation. This can happen at high elevation, where less UV rays are absorbed by the atmosphere, or near water, snow or other reflective surfaces in the environment. A few hours after exposure, patients experience burning in their eyes and sometimes intense light sensitivity.

Numerous germicidal lamps are on the market, and while they may be safe for at-home use, customers need to pay close attention to manufacturer recommendations to prevent damage to the eyes and skin.

"The patients we met were not aware of these recommendations, and many were unknowingly exposed at work" said co-author and fellow resident Anne Kunkler, M.D., B.S. "For UV-C emitting devices, it is best to leave the room while the device is on. Our patients were directly exposed to the light for various lengths of time. A few hours later, they felt discomfort and sought medical attention."

Dr. Sengillo and colleagues encourage anyone feeling eye discomfort after exposure to one of these devices to promptly seek medical attention a medical professional from an ophthalmologist.

While germicidal lamps are being purchased to protect people during the pandemic, this study did not attempt to address whether they are effective in destroying coronaviruses. "There are many COVID-19 related publications recently. It is important that we disseminate information accurately and responsibly to avoid public confusion." Dr. Sengillo and colleagues note that some UV-C emitting germicidal devices are proven to be effective in killing various microbes and viruses, but to the authors knowledge, they have not been tested against COVID-19 specifically yet. "Our study was not designed to answer that question. If you choose to use these lamps, just make sure to follow manufacturer recommendations closely to avoid unnecessary injury," said Dr. Sengillo.

Dolphins actively slow down their hearts before diving, and can even adjust their heart rate depending on how long they plan to dive for, a new study suggests. Published in Frontiers in Physiology, the findings provide new insights into how marine mammals conserve oxygen and adjust to pressure while diving.

The authors worked with three male bottlenose dolphins (Tursiops truncatus), specially trained to hold their breath for different lengths of time upon instruction. "We trained the dolphins for a long breath-hold, a short one, and one where they could do whatever they want", explains Dr Andreas Fahlman of Fundación Oceanogràfic, Valencia, Spain. "When asked to hold their breath, their heart rates lowered before or immediately as they began the breath-hold. We also observed that the dolphins reduced their heart rates faster and further when preparing for the long breath-hold, compared to the other holds".

The results reveal that dolphins, and possibly other marine mammals, may consciously alter their heart rate to suit the length of their planned dive. "Dolphins have the capacity to vary their reduction in heart rate as much as you and I are able to reduce how fast we breathe", suggests Fahlman. "This allows them to conserve oxygen during their dives, and may also be key to avoiding diving-related problems such as decompression sickness, known as "the bends"".

Understanding how marine mammals are able to dive safely for long periods of time is crucial to mitigate the health impacts of man-made sound disturbance on marine mammals. "Man-made sounds, such as underwater blasts during oil exploration, are linked to problems such as "the bends" in these animals", continues Fahlman. "If this ability to regulate heart rate is important to avoid decompression sickness, and sudden exposure to an unusual sound causes this mechanism to fail, we should avoid sudden loud disturbances and instead slowly increase the noise level over time to cause minimal stress. In other words, our research may provide very simple mitigation methods to allow humans and animals to safely share the ocean".

The practical challenges of measuring a dolphin's physiological functions, such as heart rate and breathing, have previously prevented scientists from fully understanding changes in their physiology during diving. "We worked with a small sample size of three trained male dolphins housed in professional care", Fahlman explains. "We used custom-made equipment to measure the lung function of the animals, and attached electrocardiogram (ECG) sensors to measure their heart rates".

"The close relationship between the trainers and animals is hugely important when training dolphins to participate in scientific studies", explains Andy Jabas, Dolphin Care Specialist at Siegfried & Roy's Secret Garden and Dolphin Habitat at the Mirage, Las Vegas, United States, home of the dolphins studied here. "This bond of trust enabled us to have a safe environment for the dolphins to become familiar with the specialized equipment and to learn to perform the breath-holds in a fun and stimulating training environment. The dolphins all participated willingly in the study and were able to leave at any time".

DALLAS, Nov. 24, 2020 -- Even with regular physical activity, older women (ages 50-79) who spend more waking hours in sedentary behaviors, such as sitting or lying down, have an increased risk of heart failure serious enough to require hospitalization, according to new research published today in Circulation: Heart Failure, an American Heart Association journal.

"For heart failure prevention, we need to promote taking frequent breaks from prolonged sitting or lying down, in addition to trying to achieve guideline levels of physical activity, such as those recommended by the American Heart Association," said Michael J. LaMonte, Ph.D., M.P.H., lead author of the study and research associate professor of epidemiology in the School of Public Health and Health Professions at the University at Buffalo in Buffalo, New York. "Very few studies have been published on sedentary time and heart failure risk, and even fewer have focused on older women in whom both sedentary behavior and heart failure are quite common."

To determine if increased sedentary time raised the risk of increased heart failure in older women, researchers examined the records of almost 81,000 postmenopausal women (average age of 63 years) from the Women's Health Initiative (Women's Health Initiative Observational Study). Women participating self-reported the amount of time spent daily, while awake, either sitting, lying down or being physically active.

Researchers divided participants by the total daily sedentary time (sitting and lying down combined): 6.5 hours or less; 6.6-9.5 hours; and more than 9.5 hours. Total number of daily hours spent sitting for each participant was also itemized: 4.5 hours or less; 4.6-8.5 hours; and more than 8.5 hours. None of the participants had been diagnosed with heart failure when the study began, and all were able to walk the distance of at least one block without any assistance.

During an average of 9 years of follow-up, 1,402 women were hospitalized due to heart failure. Compared with women who reported spending less than 6.5 hours per day sitting or lying down, the risk of heart failure hospitalization was:

15% higher in women reporting 6.6-9.5 hours daily spent sitting or lying down; and

42% higher in women reporting more than 9.5 hours daily spent sitting or lying down.

Compared with women who reported sitting less than 4.5 hours a day, the risk of heart failure hospitalization was:

14% higher in women who sat between 4.6 and 8.5 hours each day; and

54% higher in women who sat more than 8.5 hours a day.

"These findings are consistent with other studies confirming that people with more daily sedentary time are more likely to develop chronic health conditions such as diabetes, high blood pressure, heart attack, stroke and premature death from heart disease and other causes," LaMonte said.

The association between sedentary time and heart failure hospitalization risk remained after accounting for known heart failure risk factors such as high blood pressure, diabetes, obesity and previous heart attack. An important finding in this study was that the association between more sedentary time and a higher risk of heart failure hospitalization was found even in the subgroup of women who were the most physically active and meeting recommended activity levels.

"Our message is simple: sit less and move more. Historically, we have emphasized promoting a physically active lifestyle for heart health - and we should continue to do so! However, our study clearly shows that we also need to increase efforts to reduce daily sedentary time and encourage adults to frequently interrupt their sedentary time. This does not necessarily require an extended bout of physical activity; it might simply be standing up for 5 minutes or standing and moving one's feet in place. We do not have sufficient evidence on the best approach to recommend for interrupting sedentary time. However, accumulating data suggest that habitual activities such as steps taken during household and other activities of daily living are an important aspect of cardiovascular disease prevention and healthy aging," said LaMonte.

Although the analysis only included postmenopausal women, the findings are similar to those reported in a multiethnic study of men in California and are likely to be generalizable to men. Because the study was observational, it cannot establish a cause-and-effect relationship between sedentary time and heart failure risk. The study was limited by assessing hours of sedentary time via questionnaire rather than a wearable device to track movement. Researchers do note that they were able to find a significantly elevated risk of heart failure even after statistically controlling for confounding factors, which raises their confidence in the accuracy of the direction and magnitude of association measured.

Algorithm was trained, tested on the largest COVID-era dataset (17,002 X-ray images)

Algorithm analyzed X-ray images of lungs about 10 times faster, 1-6% more accurately than individual specialized radiologists

Algorithm is now publicly available for other researchers to continue to train it with new data

System could also potentially flag patients for isolation and testing who are not otherwise under investigation for COVID-19

'It would take seconds to screen a patient and determine if they need to be isolated,' researcher says

EVANSTON, Ill. -- Northwestern University researchers have developed a new artificial intelligence (A.I.) platform that detects COVID-19 by analyzing X-ray images of the lungs.

Called DeepCOVID-XR, the machine-learning algorithm outperformed a team of specialized thoracic radiologists -- spotting COVID-19 in X-rays about 10 times faster and 1-6% more accurately.

The researchers believe physicians could use the A.I. system to rapidly screen patients who are admitted into hospitals for reasons other than COVID-19. Faster, earlier detection of the highly contagious virus could potentially protect health care workers and other patients by triggering the positive patient to isolate sooner.

The study's authors also believe the algorithm could potentially flag patients for isolation and testing who are not otherwise under investigation for COVID-19.

The study will be published on Nov. 24 in the journal Radiology.

"We are not aiming to replace actual testing," said Northwestern's Aggelos Katsaggelos, an A.I. expert and senior author of the study. "X-rays are routine, safe and inexpensive. It would take seconds for our system to screen a patient and determine if that patient needs to be isolated."

"It could take hours or days to receive results from a COVID-19 test," said Dr. Ramsey Wehbe, a cardiologist and postdoctoral fellow in A.I. at the Northwestern Medicine Bluhm Cardiovascular Institute. "A.I. doesn't confirm whether or not someone has the virus. But if we can flag a patient with this algorithm, we could speed up triage before the test results come back."

Katsaggelos is the Joseph Cummings Professor of Electrical and Computer Engineering in Northwestern's McCormick School of Engineering. He also has courtesy appointments in computer science and radiology. Wehbe is a postdoctoral fellow at Bluhm Cardiovascular Institute at Northwestern Memorial Hospital.

A trained eye

For many patients with COVID-19, chest X-rays display similar patterns. Instead of clear, healthy lungs, their lungs appear patchy and hazy.

"Many patients with COVID-19 have characteristic findings on their chest images," Wehbe said. "These include 'bilateral consolidations.' The lungs are filled with fluid and inflamed, particularly along the lower lobes and periphery."

The problem is that pneumonia, heart failure and other illnesses in the lungs can look similar on X-rays. It takes a trained eye to tell the difference between COVID-19 and something less contagious.

Katsaggelos' laboratory specializes in using A.I. for medical imaging. He and Wehbe had already been working together on cardiology imaging projects and wondered if they could develop a new system to help fight the pandemic.

"When the pandemic started to ramp up in Chicago, we asked each other if there was anything we could do," Wehbe said. "We were working on medical imaging projects using cardiac echo and nuclear imaging. We felt like we could pivot and apply our joint expertise to help in the fight against COVID-19."

A.I. vs. human

To develop, train and test the new algorithm, the researchers used 17,002 chest X-ray images -- the largest published clinical dataset of chest X-rays from the COVID-19 era used to train an A.I. system. Of those images, 5,445 came from COVID-19-positive patients from sites across the Northwestern Memorial Healthcare System.

The team then tested DeepCOVID-XR against five experienced cardiothoracic fellowship-trained radiologists on 300 random test images from Lake Forest Hospital. Each radiologist took approximately two-and-a-half to three-and-a-half hours to examine this set of images, whereas the A.I. system took about 18 minutes.

The radiologists' accuracy ranged from 76-81%. DeepCOVID-XR performed slightly better at 82% accuracy.

"These are experts who are sub-specialty trained in reading chest imaging," Wehbe said. "Whereas the majority of chest X-rays are read by general radiologists or initially interpreted by non-radiologists, such as the treating clinician. A lot of times decisions are made based off that initial interpretation."

"Radiologists are expensive and not always available," Katsaggelos said. "X-rays are inexpensive and already a common element of routine care. This could potentially save money and time -- especially because timing is so critical when working with COVID-19."

Limits to diagnosis

Of course, not all COVID-19 patients show any sign of illness, including on their chest X-rays. Especially early in the virus' progression, patients likely will not yet have manifestations on their lungs.

"In those cases, the A.I. system will not flag the patient as positive," Wehbe said. "But neither would a radiologist. Clearly there is a limit to radiologic diagnosis of COVID-19, which is why we wouldn't use this to replace testing."

The Northwestern researchers have made the algorithm publicly available with hopes that others can continue to train it with new data. Right now, DeepCOVID-XR is still in the research phase, but could potentially be used in the clinical setting in the future.

Increased consumption of flavanols - a group of molecules which occur naturally in fruit and vegetables - can increase your mental agility, according to new research at the University of Birmingham.

A team in the University's School of Sport, Exercise and Rehabilitation Sciences found that people given a cocoa drink containing high levels of flavanols were able to complete certain cognitive tasks more efficiently than when drinking a non-flavanol enriched-drink.

The study participants also underwent non-invasive brain imaging to measure blood oxygenation levels in the brain. Working with experts at the University of Illinois, the researchers showed that participants who had consumed the flavanol-rich drink produced a faster and greater increase in blood oxygenation levels in response to artificially elevated levels of CO2 (hypercapnia).

Flavanols, a sub-group of plant flavonoids, are present in cocoa, grapes, apples, tea, berries and other foods. They are known to have a beneficial effect on cardiovascular health, but their effects on brain health are not well understood. This study, published in Scientific Reports, is the first time the cognitive effects of flavanols in young, healthy subjects and the link with brain blood oxygenation have been investigated.

Lead author, Dr Catarina Rendeiro, of the University of Birmingham's School of Sport, Exercise and Rehabilitation Sciences, explains: "We used cocoa in our experiment, but flavanols are extremely common in a wide range of fruit and vegetables. By better understanding the cognitive benefits of eating these food groups, as well as the wider cardiovascular benefits, we can offer improved guidance to people about how to make the most of their dietary choices."

In the study, 18 healthy male participants aged between 18 and 40 underwent a standard procedure to challenge the brain's blood circulation that involves breathing 5% carbon dioxide - about 100 times the normal concentration in air, producing an effect called hypercapnia. Non-invasive near-infrared spectroscopy, a technique that uses light to capture changes in blood oxygenation levels, was used to track the increases in brain oxygenation in the frontal cortex in response to this carbon dioxide challenge.

Each participant underwent the test before and after drinking a cocoa drink on two occasions and on one of those occasions, the drink was enriched with flavanols. Following the carbon dioxide test, the participants were asked to complete a number of progressively complex cognitive tests.

The researchers found that the participants who had taken the flavanol-enriched drink had the highest levels of blood oxygenation in response to hypercapnia, reaching levels up to three times higher than participants drinking the non-flavanol-enriched drink. They also achieved these elevated levels 1 minute faster than participants who drank the non-enriched cocoa.

In the cognitive tests, the researchers found significant differences in the speed and accuracy with which volunteers completed the higher complexity tasks, with volunteers who had taken the flavanol-enriched drink performing the tasks 11 per cent faster on average.

"Our results showed a clear benefit for the participants taking the flavanol-enriched drink - but only when the task became sufficiently complicated," explains Dr Rendeiro. "We can link this with our results on improved blood oxygenation - if you're being challenged more, your brain needs improved blood oxygen levels to manage that challenge. It also further suggests that flavanols might be particularly beneficial during cognitively demanding tasks".

The researchers also noted a further outcome. Within the study cohort, there was a small group who did not benefit at all from the flavanol-enriched drink in terms of blood oxygenation levels, and who also did not derive any cognitive benefit. This group was shown to have existing high levels of brain oxygenation responses to start with that were not increased further by drinking the enriched cocoa. "This may indicate that some individuals, that perhaps are already very fit, have little room for further improvement" explain Dr. Rendeiro.

"The small group of participants who did not react to the flavanol gives us additional evidence to confirm the link between increased brain blood oxygenation and cognitive ability," adds Dr Rendeiro.

PITTSBURGH, Nov. 24, 2020 - In today's issue of the Annals of Surgery, epidemiologists from the University of Pittsburgh published two separate analyses that could help guide clinicians and policymakers in counseling bariatric surgery patients to improve their quality of life for many years to come.

A study led by Gretchen White, Ph.D., assistant professor of medicine and clinical and translational science at Pitt's Institute for Clinical Research and Education, identified several patient characteristics pre- and post-surgery - such as insufficient social support and unrealistic weight loss expectations - that can predict not being satisfied long-term with Roux-en-Y gastric bypass surgery.

In a second paper, White's colleague and collaborator Wendy King, Ph.D., associate professor of epidemiology at Pitt's Graduate School of Public Health, found that higher physical activity levels after bariatric surgery lessen depressive symptoms and improve mental and physical quality of life, irrespective of weight loss.

Every year, tens of thousands of Americans who struggle with obesity undergo gastric bypass surgery to manage their body weight and comorbidities, such as diabetes. Yet, the Pitt scientists found, while most patients are at least somewhat satisfied with their surgery long-term, satisfaction decreased from 85% to 77% three to seven years post-surgery. Most patients also continue to lead sedentary lives, which contributes to weight regain and negatively affects their mental well-being.

Knowing which patients are more likely to be dissatisfied with their surgery can help doctors guide a conversation about expectations and maximize beneficial effects of the procedure, White said. Similarly, providing quantitative data that show being more physically active has positive effects on a person's well-being might help shift a patient's perspective on exercise.

"Our data support why it's important to counsel patients regarding their physical activity behaviors," said King.

"Although patients in general are not meeting physical activity recommendations post-surgery, we found a dose-response relationship - the more active patients were, the better improvement they had in depressive symptoms and health-related quality of life. Every bit matters."

Both studies analyzed data collected from 1,700 adults who underwent Roux-en-Y gastric bypass surgery between March 2006 and April 2009 and were followed for up to seven years.

In a pre-operation assessment, younger age, lower body mass index (BMI), higher percent weight loss needed to reach "dream weight," worse physical and mental health status, and less social support all independently predicted higher risk of not being satisfied with surgery. In addition, less weight loss, worsening physical and mental health status, less social support and greater depressive symptomology after the surgery were associated with not being satisfied.

"Knowing these characteristics can be useful for clinicians when talking to patients about how realistic their post-surgery expectations are, particularly when having conversations about achieving their dream weight," said White. "Modifying expectations early may lead to better satisfaction long-term."

In a separate study, King found that improvements in mental and physical health-related quality of life differed by physical activity level. By analyzing objective measures collected from wearable activity monitors -- step count, amount of time spent sedentary and amount of time spent doing moderate-to-vigorous activity -- she found that higher levels of physical activity related to improvements independent of weight loss.

In her recent work, also published in the Annals of Surgery, King showed that higher activity level predicted better weight loss and less weight regain - but that study didn't look at quality-of-life measures.

Even after the surgery, an average bariatric surgery patient leads a significantly more sedentary lifestyle than recommended by physicians.

King says this may explain why the magnitude of associations between physical activity level and improvement in health-related quality of life and depressive symptoms in their cohort was small. Still, the findings provide support for expanding measures that increase physical activity in bariatric surgery patients to influence mental and physical health outcomes.

"Most insurance providers include coverage for dietary counseling but don't reimburse expenses for hiring a health coach or getting a gym membership," said King. "There needs to be more systemic support to help patients increase their activity level and maintain an active lifestyle post-surgery."

Users expressed a stronger preference for Vype ePen 3 versus previous generation Vype ePen 2
Study supports BAT’s commitment to conduct and publish scientific research which helps build A Better Tomorrow by reducing the health impact of its business

Innovation drives significant product improvements to encourage current smokers to switch to scientifically-substantiated, reduced-risk alternatives

MONDAY, 30th NOVEMBER 2020: New research shows that Vype ePen 3, BAT’s flagship vapour product, can provide smokers with similar levels of nicotine as standard cigarettes. If used exclusively, ePen3 could help smokers avoid many of the risks associated with smoking.

The study, which has been published in Scientific Reports, compared both Vype ePen 3 and Vype ePen 2 to combustible cigarettes. It assessed a variety of e-liquids and nicotine strengths for each product, and how nicotine concentration and delivery device combined to affect user preference.

Results from the study show that Vype ePen 3 was superior to Vype ePen 2 for nicotine delivery and ranked significantly higher for user satisfaction, with the newer device scoring nearly double for likability compared to its predecessor.

The study showed that the maximum concentration of nicotine in the blood after using the Vype ePen 3 (18mg/mL protonated nicotine) was on average twice that achieved using Vype ePen 2 (18mg/mL unprotonated nicotine).

BAT is committed to building A Better Tomorrow by reducing the health impact of its business through providing a range of enjoyable and lower risk products. The company continues to be clear that combustible cigarettes pose serious health risks, and the only way to avoid these risks is not to start or to quit. BAT encourages those who would otherwise continue to smoke, to switch completely to scientifically-substantiated, reduced-risk alternatives.

This study is a part of a comprehensive programme of scientific research designed to assess and substantiate the reduced-risk potential of non-combustible products.

Dr David O’Reilly, BAT’s Director of Scientific Research said:
“The results of this study are very impressive and show how through continued innovation and research we have improved our understanding of what consumers want, but importantly how to deliver greater satisfaction with our products.

“We know that for many smokers, nicotine levels are an important factor in choosing a vaping product, particularly when initially switching. They want it to work for them, delivering the nicotine they want in a device they like. We think we have achieved this with Vype ePen 3 and hope that through continued product innovation we can encourage and enable those who would otherwise continue to smoke to switch to a reduced-risk alternative which has been scientifically substantiated.”

Study Design

This was a randomised study during which each participant was given 8 different options. The subjects were all current smokers, who were dual users of cigarettes and vapour products. Over a period of 9 days, each morning, following an overnight wash-out period (12hrs), participants used one of the available options. The level of nicotine in the blood (plasma) was assessed before, during and after their use. These data were used to evaluate changes in nicotine concentration in the user. Participants were also asked to rate their liking of each product after use.

BAT’s Vype ePen 3 was designed to provide consumers with the same high-quality product they expect but to deliver an improved user experience. Early generations of e-cigarettes often delivered lower nicotine yields than combustible cigarettes, which many associate with a lower acceptance or continuation by user.

BAT has continued to innovate the Vype ePen to develop its nicotine delivery capabilities and enhance user satisfaction. This study was designed to validate the acceptance and preference of consumers who frequently use cigarettes and vapour products.

One of the improved design features of the Vype ePen 3 is its increased power, which, together with its ability to deliver a nicotine salt, known as protonated nicotine, provides a higher aerosol mass, resulting in a greater absorption of nicotine. The ability to increase the aerosol mass also reduces the potential for irritation of the pharynx, which has been associated with higher levels of unprotonated nicotine.

Yangon, Myanmar: In September 2020, 59 percent of 1000 households surveyed in urban Yangon and 66 percent of 1000 households surveyed in the rural Dry Zone earned less than $1.90/day (a common measure of extreme poverty), according to a new study from researchers at the International Food Policy Research Institute (IFPRI). The study provides new insight into the economic impacts of the COVID-19 pandemic and strict lockdowns, as well as the additional efforts needed to protect Myanmar's vulnerable people and fragile economic recovery.

"Only 16% of our respondents were poor in January this year before the COVID crisis hit, but now 62% are poor. What is really worrying is that during the second COVID-19 wave one-third of our households said they earned zero income in the last month. That level of poverty poses huge risks for food insecurity and malnutrition" said IFPRI Senior Research Fellow and lead author of the study, Derek Headey.

"Though necessary to control the virus, lockdown periods have resulted in disastrous impacts on poverty and need to be accompanied by larger and better targeted cash transfers if Myanmar is to successfully contain the economic destruction of COVID-19's second wave."

The study, "Poverty, food insecurity, and social protection during COVID-19 in Myanmar: Combined evidence from a household telephone survey and micro-simulations," analyzed data from over 2000 women in Yangon and the Dry Zone between June and September. The findings were recently highlighted in a recent IFPRI policy seminar, "Assessments of the impact of COVID-19 on Myanmar's food security and welfare". In that seminar, officials from several government ministries acknowledged the challenge of expanding social protection in response to COVID-19, as well as the need to strengthen monitoring and evaluation of COVID-19 economic relief programs.

"The government of Myanmar has rapidly expanded social protection in 2020 and they should be commended for that. However, the scale of the second wave simply means they must do more. Over half of poor households in our survey received cash transfers by September, so unfortunately a lot of poor people are still falling through the cracks", said Headey.

The study also used a forward-looking simulation analysis to show that extreme poverty at the national level triples in lockdowns but can be reduced by cash transfers larger than those the government is currently employing. The Myanmar government has been giving 20,000 kyat transfers to most households, which can reduce national poverty by 18 percent. However, increasing those transfers to 40,000 kyat would cut the lockdown poverty rate by half.

"I think there is a growing consensus both within government and among development partners that greater social protection efforts are needed", said Headey. "We know the disease is not going away soon, so we must do better to protect households from the economic ravages of this disease."