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Hamilton, ON (June 1, 2020) - A comprehensive review of existing evidence supports physical distancing of two metres or more to prevent person-to-person transmission of COVID-19, says an international team led by McMaster University and St. Joseph's Healthcare Hamilton.

Face masks and eye protection decrease the risk of infection, too.

The systematic review and meta-analysis was commissioned by the World Health Organization. The findings were published today in The Lancet.

"Physical distancing likely results in a large reduction of COVID-19," said lead author Holger Schünemann, professor of the departments of health research methods, evidence, and impact, and medicine at McMaster.

Schünemann is co-director of the World Health Organization (WHO) Collaborating Centre for Infectious Diseases, Research Methods and Recommendations. He also is director of Cochrane Canada and McMaster GRADE Centre.

"Although the direct evidence is limited, the use of masks in the community provides protection, and possibly N95 or similar respirators worn by health-care workers suggest greater protection than other face masks," Schünemann said. "Availability and feasibility and other contextual factors will probably influence recommendations that organizations develop about their use. Eye protection may provide additional benefits."

The systematic review was conducted by a large, international collaborative of researchers, front-line and specialist clinicians, epidemiologists, patients, public health and health policy experts of published and unpublished literature in any language.

They sought direct evidence on COVID-19 and indirect evidence on related coronaviruses causative of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The team used Cochrane methods and the Grading of Recommendations, Assessment, and Evaluation (GRADE) approach which is used world-wide to assess the certainty of evidence.

They identified no randomized control trials addressing the three coronaviruses but 44 relevant comparative studies in health-care and non-health-care (community) settings across 16 countries and six continents from inception to early May 2020.

The authors noted more global, collaborative, well-conducted studies of different personal protective strategies are needed. For masks, large randomized trials are underway and are urgently needed.

The scientific lead is Derek Chu, a clinician scientist in the departments of health research methods, evidence, and impact, and medicine at McMaster and an affiliate of the Research Institute of St. Joe's Hamilton.

"There is an urgent need for all caregivers in health-care settings and non-health-care settings to have equitable access to these simple personal protective measures, which means scaling up production and consideration about repurposing manufacturing," said Chu.

"However, although distancing, face masks, and eye protection were each highly protective, none made individuals totally impervious from infection and so, basic measures such as hand hygiene are also essential to curtail the current COVID-19 pandemic and future waves."

CHAPEL HILL, NC - June 1, 2020 - In a major scientific study published in the journal Cell, scientists at the UNC School of Medicine and the UNC Gillings School of Global Public Health have characterized the specific ways in which SARS-CoV-2 - the coronavirus that causes COVID-19 - infects the nasal cavity to a great degree - replicating specific cell types - and infects and replicates progressively less well in cells lower down the respiratory tract, including the lungs.

The findings suggest the virus tends to become firmly established first in the nasal cavity, but in some cases the virus is aspirated into the lungs, where it may cause more serious disease, including potentially fatal pneumonia.

"If the nose is the dominant initial site from which lung infections are seeded, then the widespread use of masks to protect the nasal passages, as well as any therapeutic strategies that reduce virus in the nose, such as nasal irrigation or antiviral nasal sprays, could be beneficial," said study co-senior author Richard Boucher, MD, the James C. Moeser Eminent Distinguished Professor of Medicine and Director of the Marsico Lung Institute at the UNC School of Medicine.

The other co-senior author of the study was Ralph Baric, PhD, the William R. Kenan Distinguished Professor of Epidemiology at the UNC Gillings School of Public Health.

"This is a landmark study that reveals new and unexpected insights into the mechanisms that regulate disease progression and severity following SARS-CoV-2 infection," said Baric, who also holds a microbiology faculty appointment at the UNC School of Medicine. "In addition, we describe a new reverse genetic platform for SARS-CoV-2 allowing us to produce key indicator viruses that will support national vaccine efforts designed to control the spread and severity of this terrible disease."

SARS-CoV-2 initially caused outbreaks in late 2019 in China and spread around the world, infecting nearly 6 million people and killing more than 350,000. The United States accounts for almost a third of those infections and deaths.

The UNC-Chapel Hill team in their study sought to understand better a number of things about the virus, including which cells in the airway it infects, and how it gets into the lungs in the patients who develop pneumonia.

In one set of laboratory experiments, the researchers used different isolates of SARS-CoV-2 to see how efficiently they could infect cultured cells from different parts of the human airway. They found a striking pattern of continuous variation, or gradient, from a relatively high infectivity of SARS-CoV-2 in cells lining the nasal passages, to less infectivity in cells lining the throat and bronchia, to relatively low infectivity in lung cells.

The scientists also found that ACE2 - the cell surface receptor that the virus uses to get into cells - was more abundant on nasal-lining cells and less abundant on the surface of lower airway cells. This difference could explain, at least in part, why upper airway nasal-lining cells were more susceptible to infection.

Other experiments focused on TMPRSS2 and furin, two protein-cleaving enzymes found on many human cells. It's thought that SARS-CoV-2 uses those two enzymes to re-shape key virus proteins and enter human cells. The experiments confirmed that when these human enzymes are more abundant, this particular coronavirus has an increased ability to infect cells and make copies of itself.

The researchers found that the virus can infect airway-lining cells called epithelial cells, and to a limited extent the all-important "pneumocyte" lung cells that help transfer inhaled oxygen into the bloodstream. But SARS-CoV-2 infects almost no other airway cells.

Intriguingly, the virus did not infect airway-lining cells called club cells, despite the fact that these cells express both ACE2 and TMPRSS2. Moreover, the same types of airway epithelial cells from different human donors, especially lower-airway epithelial cells, tended to vary significantly in their susceptibility to infection. Such findings suggest that there are undiscovered factors in airway cells that help determine the course of infection in individuals - a course known to vary widely from mild or no symptoms all the way to respiratory failure and death.

The team mapped the sites of coronavirus infection in the lungs of several people who had died from COVID-19, and found that these sites exhibited a sort of patchiness and other characteristics consistent with the hypothesis that these sites had originated from infection higher in the airway.

The hypothesis that aspiration of oral contents into the lung is a significant contributor to COVID-19 pneumonia is consistent with the observations that people at higher risk for severe lung disease - the elderly, obese, and diabetic - are more prone to aspiration, especially at night.

The team also found that previously described individual antibodies capable of neutralizing the original SARS coronavirus of 2002 and the MERS coronavirus, which has been spreading slowly in the Middle East since 2012, did not neutralize SARS-CoV-2. However, blood serum from two of five SARS 2002 patients showed a low level but significant capability to neutralize SARS-CoV-2 infectivity in cultured cells. These data suggests that people who have been exposed to other coronaviruses may carry some other types of antibodies in their blood that provide at least partial protection against SARS-CoV-2.

"These results, using some novel and innovative methodology, open new directions for future studies on SARS-C0V-2 that may guide therapeutic development and practices for reducing transmission and severity of COVID-19," said James Kiley, Director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Boucher, Baric, and colleagues note that their study, apart from its specific findings about SARS-CoV-2 infection in the airway, involved the development of key laboratory tools - including a version of SARS-CoV-2 re-engineered to carry a fluorescent beacon - that should be useful in future investigations of the virus.

Reperfusion therapy, the gold standard for stroke treatment, helps restore blood flow after a stroke caused by a clot, preventing loss of brain tissue. However, only about 10% of stroke patients qualify, in part because of reperfusion therapy's narrow treatment window.

A recent Medical University of South Carolina study suggests that this therapy could be both safer and more effective for both motor and cognitive recovery if administered with a specialized compound that blocks the immune response. The team's preclinical findings, reported in the cover article of the May 13 Journal of Neuroscience, suggest that reducing the immune response in the brain could be a strategy for improving cognitive recovery. It could also extend the treatment window for therapy, allowing stroke specialists to help many more stroke patients.

"With reperfusion therapy, we're restoring the blood flow, which is necessary to save the tissue, but there is an ongoing inflammatory response by the immune system that is not targeted by reperfusion," said Stephen Tomlinson, Ph.D., interim chair of the Department of Microbiology and Immunology at MUSC and senior author of the article.

This could explain why, though mechanical reperfusion has a success rate of 90% in returning blood flow to the brain, only about 40% of treated patients recover enough motor and reasoning skills within three months to tend to their daily needs independently. Even those who do recover motor function can still struggle with cognitive challenges months later.

"I've seen patients who have barely any motor deficits at follow-up, but they're really struggling in their daily life in terms of memory, behavioral consequences and language," said lead author Ali Alawieh, M.D., Ph.D., who completed his graduate studies at MUSC and is now a resident in neurosurgery at Emory University School of Medicine.

Tomlinson and Alawieh think the immune response in the brain is the culprit.

During a stroke, the oxygen and energy supply to the brain is cut off by a clot, causing brain tissue to become stressed and die rapidly.

Just as it is with a cut to the knee, the immune system is activated to heal the wound, which includes clearing the dead tissue.

A family of special immune proteins called complement proteins help to guide and promote this immune response in the damaged areas.

In a 2018 article in Science Translational Medicine, Tomlinson and Alawieh showed that these complement proteins flagged both dead tissue and stressed brain cells for removal.

The stressed brain cells were not yet dead, only damaged by lack of oxygen and energy. As the goal of stroke treatment is to save as much brain tissue as possible to lessen overall damage, this was a concerning result, as it meant salvageable tissue was being destroyed by the immune system.

Therefore, Tomlinson and his team developed a complement protein blocker, named B4Crry, which acts only at the site of stroke injury. This compound blinds the complement proteins to the signals of stressed brain cells, saving the stressed tissue and reducing overall brain damage in a preclinical stroke model.

In the current study, Tomlinson and Alawieh hypothesized that pairing reperfusion therapy and B4Crry would significantly improve stroke recovery beyond reperfusion therapy alone. In particular, they hypothesized this combination treatment would improve cognitive recovery.

As Tomlinson's team expected, reperfusion therapy alone did improve recovery of coordinated movements such as walking in a preclinical model of stroke. With the addition of B4Crry to treatment, coordinated movement improved even faster, with greater recovery seen as early as three days after the stroke.

The improvements to learning and memory were even greater than those seen with motor functions.

Reperfusion therapy alone was equal to no treatment at all for learning and memory recovery after stroke. However, when B4Crry was added to their treatments, mice had greatly improved cognitive recovery, making three times fewer errors on a learning and memory task.

Tomlinson's team further probed into why the addition of B4Crry, and the subsequent reduction of the brain's immune response, aided cognitive recovery so greatly.

They found that after stroke, brain immune cells called microglia began eating the connections between stressed brain cells. Immune system complement proteins were marking these connections for destruction because they displayed the stressed cell signal. Without these connections, brain cells cannot communicate efficiently, and overall brain function decreases.

B4Crry concealed the cells' stress signals from the complement proteins and thereby saved the connections between neurons. Preserving connectivity improved learning and memory brain function after stroke.

A complement inhibitor such as B4Crry might also help stroke specialists overcome the biggest hurdle for reperfusion therapy: the short treatment window.

Tomlinson's team showed that after clot removal adding B4Crry to reperfusion therapy reduced the potential for hemorrhage, or excessive bleeding, even with treatment given up to six hours after the stroke. These findings suggest that complement inhibition could not only make reperfusion therapy safer but extend its treatment window, making it available for many more stroke patients.

Alawieh is excited about the future use of complement inhibition in the clinic.

"Our next step is to see how complement inhibitors work with comorbidities, such as old age, smoking and diabetes, in a preclinical study," he explained. "Collectively, this information will help us design the best clinical trial when we move to humans."

Tomlinson's team at MUSC is also testing the potential for complement inhibitors in other brain injuries, such as traumatic brain injury.

"We have shown that we can administer complement inhibitors as far as two months after a traumatic brain injury and see improvements in cognitive recovery," said Tomlinson. "This is something I'm actually quite excited about. It means that months after an initial event, complement inhibitors could still be beneficial to cognitive recovery after brain injuries, including strokes."

Fluctuating estrogen levels may make alcohol more rewarding to female mice, according to new research in JNeurosci. Untangling the involved signaling pathways could unveil sex-based treatments for alcohol use disorders.

Recreational use of alcohol can escalate into something more dire such as excessive binge drinking or even an alcohol use disorder. Women are more susceptible than men to these negative effects of alcohol, potentially because of the sex hormone estrogen.

Vandegrift et al. activated estrogen receptors in mice and tracked how the activation influenced alcohol's effects on the brain. The research team targeted two subtypes of estrogen receptors in the ventral tegmental area (VTA), a brain region involved in drug reward and reinforcement. Activating the α estrogen receptor subtype caused neurons to fire even more than normal in response to alcohol. Increased neuron firing releases more dopamine and could translate to a greater feeling of reward when drinking, making abuse more likely when estrogen levels rise. The scientists then reduced the number of estrogen receptors in the VTA of both male and female mice. This decreased binge drinking behavior in female mice but had no effect on male mice -- even though they have estrogen in their brains, too.

What happens in the hippocampus even before people attempt to form memories may impact whether they remember.

A new study analyzed neuronal recordings from the brains of epilepsy patients while they committed a series of words to memory. When the firing rates of hippocampal neurons were already high before the patients saw a word, they were more successful in encoding that word and remembering it later.

The findings suggest that the hippocampus might have a "ready-to-encode" mode that facilitates remembering. The study, published in the Proceedings of the National Academy of Sciences with University of California San Diego researcher Zhisen Urgolites as first author, also suggests that when hippocampal neurons are not already spiking very much, novel information is more likely to be poorly encoded and later forgotten.

"A key question going forward is how to put our brains into 'encoding mode' when we wish to do so," said John Wixted, professor of psychology at UC San Diego, and one of the lead authors on the paper.

"'Encoding mode'," Wixted said, "is more than simply paying attention to the task at hand. It is paying attention to encoding, which selectively ramps up activity in the part of the brain that is the most important for making new memories: the hippocampus. Since we know, based on earlier research, that people can actively suppress memory formation, it might be possible for people to get their hippocampus ready to encode as well. But how one might go about doing that, we just don't know yet."

Neuronal recordings from the hippocampus, amygdala, anterior cingulate and prefrontal cortex were collected from 34 epilepsy patients while they underwent clinical monitoring at Barrow Neurological Institute. The experiments were originally performed in Peter Steinmetz's laboratory between 2007 and 2014 when he was at the institute. The data have since been maintained at the Neurtex Brain Research Institute, where Steinmetz is chief scientific officer, and the present research team is newly analyzing the data.

During the experiments, the patients either saw or listened to a steady stream of words and had to indicate whether each word was novel or a repeat. At first, all the words were novel, but after a while most words repeated.

The researchers calculated the average number of times a neuron fired in response to every word the study participants saw or heard. They also calculated the neuronal firing rates immediately preceding each word. Only the average firing rate in the hippocampus approximately one second before seeing or hearing a word for the first time was important: That neuronal activity predicted whether the participants remembered or forgot the word when it was repeated later on.

"If a person's hippocampal neurons were already firing above baseline when they saw or heard a word, their brain was more likely to successfully remember that word later," said Stephen Goldinger, professor of psychology at Arizona State University.

The neuronal activity measured in the amygdala, anterior cingulate, and prefrontal cortex did not predict task performance.

"We think new memories are created by sparse collections of active neurons, and these neurons get bundled together into a memory. This work suggests that when a lot of neurons are already firing at high levels, the neuronal selection process during memory formation works better," Goldinger said.

Climate engineering provides solutions that directly affect the incoming radiation from the sun and are able to rapidly offset the temperature increase. These technologies open new scenarios on the management of the risks related to climate change, on the need to contain the warming of the planet within two degrees Celsius as defined by international agreements, on the strategies that individual states, or coalitions of states, can put in place to avoid negative impacts related to climate.

An international team of scientists conducted the first-of-its-kind laboratory experiment to test how behavioural and strategic factors shape the economic outcomes of climate geoengineering.

Belonging to different research groups in Italy (RFF-CMCC European Institute of the Economics and the Environment, Fondazione Centro Euro-Mediterraneo sui Cambiamenti Climatici, Università Bocconi, Università di Bologna, University of Milano-Bicocca, and Politecnico di Milano), researchers have taken into consideration the governance challenges arising from the prospects opened by geoengineering, and the results are reported in the article "Solar geoengineering may lead to excessive cooling and high strategic uncertainty", recently published in the journal PNAS (Proceedings of the National Academy of Science of the United States).

Based on a geoengineering model, the experiment conducted by the research group showed that countries wanting a cooler climate employ geoengineering to reach it even if by doing so they impose it on others who would prefer a warmer climate - an outcome called 'free driving'. This strategic, rational behaviour leads to too much geo-engineering, and results in increased inequalities and economic losses. The experiment also studied the possibility of retaliation through counter-geoengineering solutions. Here, results how behavioural motives lead to high variability in geoengineering outcomes, with detrimental economic and equity consequences.

"Miscoordination among countries increases under counter-geoengineering," says Anna Abatayo, research fellow at Bocconi University.

Riccardo Ghidoni, Assistant Professor at the University Milano-Bicocca, says: "We find that retaliation through counter-geoengineering is particularly risky when there are many decision makers. This is relevant for international negotations with multiple parties".

"Solar geoengineering brings us into uncharted territory", says Marco Casari, Professor of Economics at Bologna University, "and our experiment can shed light on what to expect in those new situations. If major issues emerge, the rules of governance could be corrected before field implementation. I like the analogy with aeronautical engineering: prototypes of new airplanes go first in 'wind tunnels' to identify and remove design flows. Our experiments serve a similar purpose in the realm of the social sciences".

"This paper shows the relevance of the human factor -both rational and irrational- for climate decision making in general not just climate engineering", says Massimo Tavoni, director of the RFF-CMCC European Institute of the Economics and the Environment and Professor at Politecnico di Milano. "It highlights the necessity of strong institutions to solve global environmental challenges".

CAMBRIDGE, MA -- One promising strategy to treat cancer is stimulating the body's own immune system to attack tumors. However, tumors are very good at suppressing the immune system, so these types of treatments don't work for all patients.

MIT engineers have now come up with a way to boost the effectiveness of one type of cancer immunotherapy. They showed that if they treated mice with existing drugs called checkpoint inhibitors, along with new nanoparticles that further stimulate the immune system, the therapy became more powerful than checkpoint inhibitors given alone. This approach could allow cancer immunotherapy to benefit a greater percentage of patients, the researchers say.

"These therapies work really well in a small portion of patients, and in other patients they don't work at all. It's not entirely understood at this point why that discrepancy exists," says Colin Buss PhD '20, the lead author of the new study.

The MIT team devised a way to package and deliver small pieces of DNA that crank up the immune response to tumors, creating a synergistic effect that makes the checkpoint inhibitors more effective. In studies in mice, they showed that the dual treatment halted tumor growth, and in some cases, also stopped the growth of tumors elsewhere in the body.

Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, and a member of MIT's Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science, is the senior author of the paper, which appears this week in the Proceedings of the National Academy of Sciences.

Removing the brakes

The human immune system is tuned to recognize and destroy abnormal cells such as cancer cells. However, many tumors secrete molecules that suppress the immune system in the environment surrounding the tumor, rendering the T cell attack useless.

The idea behind checkpoint inhibitors is that they can remove this "brake" on the immune system and restore T cells' ability to attack tumors. Several of these inhibitors, which target checkpoint proteins such as CTLA-4, PD-1, and PD-L1, have been approved to treat a variety of cancers. These drugs work by turning off checkpoint proteins that prevent T cells from being activated.

"They work incredibly well in some patients, and they've given what some would call cures, for about 15 to 20 percent of patients with particular cancers," Bhatia says. "However, there's still a lot more to do to open up the possibility of using this approach for more patients."

Some studies have found that combining checkpoint inhibitors with radiation therapy can make them more effective. Another approach that researchers have tried is combining them with immunostimulatory drugs. One such class of drugs is oligonucleotides -- specific sequences of DNA or RNA that the immune system recognizes as foreign.

However, clinical trials of these immunostimulatory drugs have not been successful, and one possible reason is that the drugs are not reaching their intended targets. The MIT team set out to find a way to achieve more targeted delivery of these immunostimulatory drugs, allowing them to accumulate at tumor sites.

To do that, they packaged oligonucleotides into tumor-penetrating peptides that they had previously developed for delivering RNA to silence cancerous genes. These peptides can interact with proteins found on the surfaces of cancer cells, helping them to specifically target tumors. The peptides also include positively charged segments that help them penetrate cell membranes once they reach the tumor.

The oligonucleotides that Bhatia and Buss decided to use for this study contain a specific DNA sequence that often occurs in bacteria but not in human cells, so that the human immune system can recognize it and respond. These oligonucleotides specifically activate immune cell receptors called toll-like receptors, which detect microbial invaders.

"These receptors evolved to allow cells to recognize the presence of pathogens like bacteria," Buss says. "That tells the immune system that there's something dangerous here: Turn on and kill it."

A synergistic effect

After creating their nanoparticles, the researchers tested them in several different mouse models of cancer. They tested the oligonucleotide nanoparticles on their own, the checkpoint inhibitors on their own, and the two treatments together. The two treatments together produced the best results, by far.

"When we combined the particles with the checkpoint inhibitor antibody, we saw a vastly improved response relative to either the particles alone or the checkpoint inhibitor alone," Buss says. "When we treat these mice with particles and the checkpoint inhibitor, we can stop their cancer from progressing."

The researchers also wondered whether they could stimulate the immune system to target tumors that had already spread through the body. To explore that possibility, they implanted mice with two tumors, one on each side of the body. They gave the mice the checkpoint inhibitor treatment throughout the entire body but injected the nanoparticles into only one tumor. They found that once T cells had been activated by the treatment combination, they could also attack the second tumor.

"We saw some signs that you could stimulate in one location and then get a systemic response, which was encouraging," Bhatia says.

The researchers now plan to perform safety testing of the particles, in hopes of further developing them to treat patients whose tumors don't respond to checkpoint inhibitor drugs on their own. To that end, they are working with Errki Ruoslahti of the Sanford Burnham Prebys Medical Discovery Institute, who originally discovered the tumor-penetrating peptides. A company that Ruoslahti founded has already taken other versions of the tumor-penetrating peptides into human clinical trials to treat pancreatic cancer.

"That makes us optimistic about the potential to scale up, manufacture them, and advance them to help patients," Bhatia says.

A study conducted in Sydney during the early epidemic stage of COVID-19 has found an association between lower humidity and an increase in locally acquired positive cases. Researchers discovered a 1 percent decrease in humidity could increase the number of COVID-19 cases by 6 percent.

The research led by Professor Michael Ward, an epidemiologist in the Sydney School of Veterinary Science at the University of Sydney, and two researchers from our partner institution Fudan University School of Public Health in Shanghai, China, is the first peer-reviewed study of a relationship between climate and COVID-19 in the southern hemisphere.

"COVID-19 is likely to be a seasonal disease that recurs in periods of lower humidity. We need to be thinking if it's winter time, it could be COVID-19 time," said Professor Ward.

The study is published today in Transboundary and Emerging Diseases.

Further studies - including during winter in the southern hemisphere - are needed to determine how this relationship works and the extent to which it drives COVID-19 case notification rates.

Previous research has identified a link between climate and occurrence of SARS-CoV cases in Hong Kong and China, and MERS-CoV cases in Saudi Arabia, and a recent study on the COVID-19 outbreak in China found an association between transmission and daily temperature and relative humidity.

"The pandemic in China, Europe and North America happened in winter so we were interested to see if the association between COVID-19 cases and climate was different in Australia in late summer and early autumn," Professor Ward said.

"When it comes to climate, we found that lower humidity is the main driver here, rather than colder temperatures," Professor Ward said. "It means we may see an increased risk in winter here, when we have a drop in humidity. But in the northern hemisphere, in areas with lower humidity or during periods when humidity drops, there might be a risk even during the summer months. So vigilance must be maintained."

Why humidity matters

Professor Ward said there are biological reasons why humidity matters in transmission of airborne viruses.

"When the humidity is lower, the air is drier and it makes the aerosols smaller," he said. "When you sneeze and cough those smaller infectious aerosols can stay suspended in the air for longer. That increases the exposure for other people. When the air is humid and the aerosols are larger and heavier, they fall and hit surfaces quicker."

Method

Professor Ward and his team studied 749 locally acquired cases of COVID-19 - mostly in the Greater Sydney area of the state of New South Wales - between February 26 and March 31. The team matched the patients' postcodes with the nearest weather observation station and studied the rainfall, temperature and humidity for the period January to March 2020.

The study found lower humidity was associated with an increased case notifications; a reduction in relative humidity of 1 percent was predicted to be associated with an increase of COVID-19 cases by 6 percent.

"This means we need to be careful coming into a dry winter," Professor Ward said, adding that the average humidity in Sydney is lowest in August.

"Even though the cases of COVID-19 have gone down in Australia, we still need to be vigilant and public health systems need to be aware of potentially increased risk when we are in a period of low humidity," Professor Ward said. "Ongoing testing and surveillance remain critical as we enter the winter months, when conditions may favour coronavirus spread."

MANHATTAN, KANSAS -- An analysis of more than 200,000 spiral galaxies has revealed unexpected links between spin directions of galaxies, and the structure formed by these links might suggest that the early universe could have been spinning, according to a Kansas State University study.

Lior Shamir, a K-State computational astronomer and computer scientist, presented the findings at the 236th American Astronomical Society meeting in June 2020. The findings are significant because the observations conflict with some previous assumptions about the large-scale structure of the universe.

Since the time of Edwin Hubble, astronomers have believed that the universe is inflating with no particular direction and that the galaxies in it are distributed with no particular cosmological structure. But Shamir's recent observations of geometrical patterns of more than 200,000 spiral galaxies suggest that the universe could have a defined structure and that the early universe could have been spinning. Patterns in the distribution of these galaxies suggest that spiral galaxies in different parts of the universe, separated by both space and time, are related through the directions toward which they spin, according to the study.

"Data science in astronomy has not just made astronomy research more cost-effective, but it also allows us to observe the universe in a completely different way," said Shamir, also a K-State associate professor of computer science. "The geometrical pattern exhibited by the distribution of the spiral galaxies is clear, but can only be observed when analyzing a very large number of astronomical objects."

A spiral galaxy is a unique astronomical object because its visual appearance depends on the observer's perspective. For instance, a spiral galaxy that spins clockwise when observed from Earth, would seem to spin counterclockwise when the observer is located in the opposite side of that galaxy. If the universe is isotropic and has no particular structure -- as previous astronomers have predicted -- the number of galaxies that spin clockwise would be roughly equal to the number of galaxies that spin counterclockwise. Shamir used data from modern telescopes to show that this is not the case.

With traditional telescopes, counting galaxies in the universe is a daunting task. But modern robotic telescopes such as the Sloan Digital Sky Survey, or SDSS, and the Panoramic Survey Telescope and Rapid Response System, or Pan-STARRS, are able to image many millions of galaxies automatically as they survey the sky. Machine vision can then sort millions of galaxies by their spin direction far faster than any person or group of people.

When comparing the number of galaxies with different spin directions, the number of galaxies that spin clockwise is not equal to the number of galaxies that spin counterclockwise. The difference is small, just over 2%, but with the high number of galaxies, there is a probability of less than 1 to 4 billion to have such asymmetry by chance, according to Shamir's research.

The patterns span over more than 4 billion light-years, but the asymmetry in that range is not uniform. The study found that the asymmetry gets higher when the galaxies are more distant from Earth, which shows that the early universe was more consistent and less chaotic than the current universe.

But the patterns do not just show that the universe is not symmetric, but also that the asymmetry changes in different parts of the universe, and the differences exhibit a unique pattern of multipoles.

"If the universe has an axis, it is not a simple single axis like a merry-go-round," Shamir said. "It is a complex alignment of multiple axes that also have a certain drift."

The concept of cosmological multipoles is not new. Previous space-based observatories -- such as the Cosmic Background Explorer, or COBE, satellite; the Wilkinson Microwave Anisotropy Probe, or WMAP mission; and the Planck observatory -- showed that the cosmic microwave background, which is electromagnetic radiation from the very early universe, also exhibits multiple poles. But the measurement of the cosmic microwave background is sensitive to foreground contamination -- such as the obstruction of the Milky Way -- and cannot show how these poles changed over time. The asymmetry between spin directions of spiral galaxies is a measurement that is not sensitive to obstruction. What can obstruct galaxies spinning in one direction in a certain field will necessarily also obstruct galaxies spinning in the opposite way.

"There is no error or contamination that could exhibit itself through such unique, complex and consistent patterns," Shamir said. "We have two different sky surveys showing the exact same patterns, even when the galaxies are completely different. There is no error that can lead to that. This is the universe that we live in. This is our home."

Cambridge, Mass. - It is well known that rates of transmission of some respiratory viruses, including influenza, tend to fall during the summer months. As COVID-19 has spread across the globe, questions have been raised about whether warming temperatures, humidity and UV index might slow, or even halt, the spread of SARS-CoV-2, the virus that causes COVID-19. These effects on virus transmission will be important to understand as warmer months ease in and states across the country consider and implement reopening plans.

To answer these questions, researchers at Mount Auburn Hospital looked at the impact of temperature, precipitation, and UV index on COVID-19 case rates in the United States during the spring months of 2020. Published in the journal Clinical Infectious Diseases, the findings reveal that while the rate of COVID-19 incidence does decrease with warmer temperatures up until 52 degrees F, further warmer temperatures do not decrease disease transmission significantly. A higher UV index also assists in slowing the growth rate of new cases, but the overall impact remains modest. Precipitation patterns did not appear to have any effect on virus transmission.

The research team analyzed daily reported cases of SARS-CoV-2 infection across the United States from January 22, 2020 through April 3, 2020, as tracked by John Hopkins University's COVID-19 Dashboard, and estimated associations between temperature, precipitation, UV Index, as tracked from the National Centers for Environmental Information, and rate of case increase.

"While the rate of virus transmission may slow down as the maximum daily temperature rises to around 50 degrees, the effects of temperature rise beyond that don't seem to be significant," said first author Shiv T. Sehra, MD, Director of the Internal Medicine Residency Program at Mount Auburn Hospital and Assistant Professor of Medicine at Harvard Medical School. "Based on our analysis, the modest association suggests that it is unlikely that disease transmission will slow dramatically in the summer months from the increase in temperature alone."

In addition to examining how temperature changes between January and April of 2020 impacted the spread of SARS-CoV-2, the team modeled what the impact would be if a state remained within a maximum temperature range, demonstrating five different scenarios: less than 30 degrees F, between 30-40 degrees F, between 40-50 degrees F, between 50-60 degrees F, and over 60 degrees F. The lowest rate of new cases was observed on days where the temperature was above 50 degrees F five days earlier. The highest increase in infection rates were detected on days when the maximum temperature was below 30 degrees F.

The Centers for Disease Control and Prevention has stated that the COVID-19 pandemic may worsen in the fall and winter as temperatures drop. "Our results are in line with those predictions," Sehra noted. "We also caution that the disease may get worse in the fall and winter months."

While previous studies on SARS-CoV-2 in the lab setting showed that the virus survives for shorter duration in higher temperatures and is inactivated by UV light, few have looked at the effects of temperature, precipitation or UV light on the rates of virus transmission in the community.

"To the best of our knowledge, this is probably one of the first peer-reviewed studies that examine the influence that temperature, precipitation and UV light have in terms of virus transmission in the general population across the United States," said Sehra.

The study had several important limitations and considerations. Climate data for state capitals was extrapolated to the entire state, as sourced from National Centers for Environmental Information. Also, the data in the study was collected when much of the country had maximum daily temperatures below 70 degrees F. While average summer temperatures will far exceed that in most of the country, this study cannot evaluate what effect, if any, temperatures over 70-75 degrees F may have on virus transmission.

The researchers note that during the pandemic, reporting methods of COVID-19 patient numbers have varied geographically. Containment strategies, stay-at-home policies, and access to testing, variability of testing formats, and number of tests performed also varied across states, though the study did try to account for these factors.

Some of the most essential processes on the planet involves water and energy entering and leaving cells.

The cellular doormen responsible for this access are known as aquaporins and glucose transporters, two families of proteins that facilitate the rapid and yet selective flux of water, glucose and other small substances across biological membranes.

Aquaporins are present in all kingdoms of life, demonstrating their central role in maintaining the health of all organisms. The first aquaporin was discovered in 1992, earning its discoverer, Peter Agre, the Nobel Prize in Chemistry in 2003. Since that time, more than 450 individual aquaporins have been identified.

Computer-based experiments -- in particular molecular dynamics (MD) simulations -- have proven to be important in determining how materials permeate through channel proteins at the molecular level.

According to Liao Chen, textbook descriptions of glucose transporters have underestimated the complexity of how these proteins operate. Experiments and x-ray crystallography can only capture so much details, and computer simulations have been limited in their ability to model large-scale systems that include the membrane complexities involved in the gating, and other factors.

Chen has studied this problem using supercomputers at the Texas Advanced Computing Center (TACC) for more than a decade, with increasing accuracy and complexity.

"As a theoretical physicist, I firmly believe in what Richard Feynman said: that everything that living things do can be understood in terms of the jigglings and wigglings of atoms," Chen said. "We've tried to build a bridge from the jiggling and wiggling of millions of atoms to very simple deterministic behavior of biological systems."

Since 2019, he has applied the modeling power of Frontera -- one of the most powerful supercomputers in the world -- to investigate how the aquaporins and glucose transporters in human red blood cells move water and glucose in and out of the cell.

"We're building models of membrane proteins from atoms including their immediate environment in the membrane," Chen said. "The membrane is composed of lipids and the inner and outer leaflets are asymmetrical. Qualitatively, we understand how water and glucose move, but no one has modeled the membrane correctly for quantitative accuracy that is a norm in other branches of physics. We are moving in that direction."

Chen's research has found significant differences between the results produced by simple models and the more realistic ones he uses.

"With Frontera, we have been able to get closer to reality and achieve quantitative agreement between experiments and computer simulations," he said.

Beyond the basic biological function of aquaporins and glucose transporters, these proteins are implicated in diseases such as de Vivo's syndrome, a neurological disorder, and multiple forms of cancer. In April 2020, Chen published a paper in Frontiers in Physics applying the research to a disease-causing parasite that is a useful analogue for the virus that causes malaria in humans. Researchers are also investigating the manipulation of these proteins as a treatment for certain types of cancers -- limiting the availability of needed nutrients to stop the growth of tumors.

Water movement in and out of cells involves the simplest of membrane transporters. However, the glucose transporters that conduct glucose -- which provides the energy needed by all cells -- across cell membranes are more complicated.

"The mechanism of how glucose is transported is controversial, but I believe we are now very close to the answer," Chen said.

It was long assumed glucose transporters obey the alternating access theory like many other proteins in the major facilitator superfamily. Proteins in this superfamily have two groups of transmembrane helices that are theorized to swing relative to each other. In that way, the protein can be open on the extracellular side to allow a sugar into the protein. Then the two groups swing so that protein becomes open to the intracellular side allowing the sugar to leave the protein and enter the cytoplasm. The protein keeps alternating between the conformations open to the outside and open to the inside to ferry the energy needed in cellular metabolism.

However, glucose transporters are distinct from the other members of this huge superfamily of transporter proteins. Unlike the other members that are active transporters with energy supplies available to them, glucose transporters are passive facilitators; they do not have an energy supply to enable them to operate. Chen believed glucose transporters may not obey the alternating access theory and started to examine glucose transporters 1 and 3 very closely.

"Our studies indicate that once we put this simple transporter in cells, if you use an asymmetrical membrane, the transporter does not have to go through an alternating access mechanism," Chen said. "It actually has a gate on the extracellular side that fluctuates between being open and closed based on body temperature. So that's an example of diversity in the mechanism of transporter proteins."

Chen has published two papers on this specific topic so far. Writing in ACS Chem. Neuroscience, his team provided a quantitative study of glucose transporter 3, which is common in the central nervous system and thus called the neuronal glucose transporter. In a more recent paper in Biochemical and Biophysical Research Communications, they suggested the new possibility for how glucose transporters operate.

Chen's team also does laboratory experiments to see the overall behavior of cell, and to get a baseline truth to compare his models to. But supercomputers are required to get to the specific mechanistic details.

In April 2020, Chen was awarded 200,000 node hours on Frontera to model the protein channels in greater detail.

"On Frontera, each core is faster and the system is massive, so we can model larger systems a lot quicker," he said. "Larger systems are a must. When you deal with small systems, you're not close to reality."

ITHACA, N.Y. - Men participated more in an active learning course in science, technology, engineering and math, while women reported lower perceptions of their scientific abilities, were more aware of gender identity and more likely to feel judged based on gender, a new Cornell-led study has found.

In "Gender Differences in Student Participation in an Active Learning Classroom," published May 26 in CBE-Life Sciences Education, researchers in the Department of Ecology and Evolutionary Biology (EEB), in the College of Arts and Sciences, analyzed student behavior in an introductory biology course at Cornell.

These results suggest that "active learning in itself is not a panacea for STEM equity," the researchers wrote. "Rather, to maximize the benefits of active learning pedagogy, instructors should make a concerted effort to use teaching strategies that are inclusive and encourage equitable participation by all students."

Doctoral students Stepfanie Aguillon and Gregor-Fausto Siegmund led the study, which included former EEB graduate student teaching assistants, lecturers and postdoctoral fellows. Cissy Ballen, a former EEB postdoc who's now at Auburn University, and Abby Drake, a senior lecturer in the department and an Active Learning Initiative fellow, were instrumental in developing the study.

The "flipped classroom" approach of the active learning model incorporates in-class activities, group work, real-time surveys and other tools to help students apply knowledge through deliberate practice during class time.

Numerous studies documenting the benefits of active learning for many demographic groups have led to a shift in teaching that requires students to interact more in the classroom, particularly in STEM courses.

"A lot of work has been done showing that the transition to active learning in this course was beneficial for students from underrepresented backgrounds," said Aguillon, who was a teaching assistant in the course during the study. "We wanted to go one step further to understand how students actually experience the classroom environment once active learning methods are used."

They focused on student gender because research suggests women participate less in interactions in front of whole classes. They sought to determine whether active learning strategies such as structured activities or clicker questions promote equitable participation by all students.

To find out, researchers observed students in this course over two semesters, recording students' interactions with the instructor across seven categories, including unprompted comments and questions; prompted responses from individuals; prompted responses from groups; and student interaction with the instructor during small group activities.

The researchers also collected student grades and conducted surveys to assess students' awareness of gender identity in the classroom (salience of gender identity) and to measure their perceptions of their own capability to undertake science tasks (self-efficacy).

Before the study, the researchers hypothesized that active learning practices such as peer discussion and clicker questions would result in parity between genders. Instead, they observed that men participated more than women in all interaction types except for group work (in one semester of the study). This result, together with men's higher rates of scientific self-efficacy and relative lack of worry about gender stereotypes, points to a need to further adjust participation plans in active learning classroom, they said.

"Research from Cornell and elsewhere suggests that active learning reduces performance gaps in STEM classes, and we thought that might translate to reducing participation gaps, as well," said Siegmund. "For us, it emphasizes that the instructor is really setting the stage for the students to act - and what that stage looks like can matter."

This study grew out of a project with Cornell's Scholarship of Teaching and Learning Program, now part of the Future Faculty and Academic Careers program.

A team of researchers, led by astrophysicist Sumner Starrfield of Arizona State University (ASU), has combined theory with both observations and laboratory studies and determined that a class of stellar explosions, called classical novae, are responsible for most of the lithium in our galaxy and solar system.

The results of their study have been recently published in the Astrophysical Journal of the American Astronomical Society.

"Given the importance of lithium to common uses like heat-resistant glass and ceramics, lithium batteries and lithium-ion batteries, and mood altering chemicals; it is nice to know where this element comes from," says Starrfield who is a Regents Professor with ASU's School of Earth and Space Exploration and a Fellow of the American Astronomical Society. "And improving our understanding of the sources of the elements out of which our bodies and the solar system are made is important."

The team has gone on to determine that a fraction of these classical novae will evolve until they explode as supernovae of type Ia. These exploding stars become brighter than a galaxy and can be discovered at very large distances in the universe.

As such, they are being used to study the evolution of the universe and were the supernovae used in the mid-1990's to discover Dark Energy, which is causing the expansion of the universe to accelerate. They also produce much of the iron in the galaxy and solar system, an important constituent of our red blood cells, which carry oxygen throughout the body.

Classical Novae

The formation of the universe, commonly referred to as the "Big Bang," primarily formed the elements hydrogen, helium, and a little lithium. All the other chemical elements, including the majority of lithium, are formed in stars.

Classical novae are a class of stars consisting of a white dwarf (a stellar remnant with the mass of the Sun but the size of Earth) and a larger star in close orbit around the white dwarf.

Gas falls from the larger star onto the white dwarf and when enough gas has accumulated on the white dwarf, an explosion, or nova, occurs. There are about 50 explosions per year in our galaxy and the brightest ones in the night sky are observed by astronomers world-wide.

Simulations, Observations, and Meteorites

Several methods were used by the authors in this study to determine the amount of lithium produced in a nova explosion. They combined computer predictions of how lithium is created by the explosion, how the gas is ejected and what its total chemical composition should be, along with telescope observations of the ejected gas, to actually measure the composition.

Starrfield used his computer codes to simulate the explosions and worked with co-author and American Astronomical Fellow Charles E. Woodward of the University of Minnesota and co-author Mark Wagner of the Large Binocular Telescope Observatory in Tucson and Ohio State to obtain data on nova explosions using ground-based telescopes, orbiting telescopes, and the Boeing 747 NASA observatory called SOFIA.

Co-authors and nuclear astrophysicists Christian Iliadis of the University of North Carolina at Chapel Hill and W. Raphael Hix of the Oak Ridge National Laboratory and University of Tennessee, Knoxville provided insight into the nuclear reactions within stars that were essential to solving the differential equations needed for this study.

"Our ability to model where stars get their energy depends on understanding nuclear fusion where light nuclei are fused to heavier nuclei and release energy," says Starrfield. "We needed to know under what stellar conditions we can expect the nuclei to interact and what the products of their interaction are."

Co-author and isotope cosmochemist Maitrayee Bose of ASU's School of Earth and Space Exploration analyzes meteorites and interplanetary dust particles that contain tiny rocks that formed in different kinds of stars.

"Our past studies have indicated that a small fraction of stardust in meteorites formed in novae," says Bose. "So the valuable input from that work was that nova outbursts contributed to the molecular cloud that formed our solar system." Bose further states that their research is predicting very specific compositions of stardust grains that form in nova outbursts and have remained unchanged since they were formed.

"This is ongoing research in both theory and observations," says Starrfield. "While we continue to work on theories, we're looking forward to when we can use NASA's James Webb Space Telescope and the Nancy Grace Roman Telescope to observe novae and learn more about the origins of our universe."

Plant biologists have long sought a deeper understanding of foundational processes involving kinases, enzymes that catalyze key biological activities in proteins. Analyzing the processes underlying kinases in plants takes on greater urgency in today's environment increasingly altered by climate warming.

Certain "SnRK2" kinases (sucrose-non-fermenting-1-related protein kinase-2s) are essential since they are known to be activated in response to drought conditions, triggering the protective closure of small pores on leaf surfaces known as stoma. These pores allow carbon dioxide to enter leaves, but plants also lose more than 90 percent of their water by evaporation through them. Pore opening and closing functions help optimize growth and drought tolerance in response to changes in the environment.

Now, plant biologists at the University of California San Diego have developed a new nanosensor that allows researchers to monitor SnRK2 protein kinase activity in live plant cells. The SnRK2 activity sensor, or "SNACS," is described in the journal eLife.

Prior efforts to dissect protein kinase activities involved a tedious process of grinding up plant tissues and measuring kinase activities through cell extracts. More than 100 leaves were required per experiment for analyses of the stomatal pore forming "guard cells." SNACS now allows researchers to analyze changes in real time as they happen.

"Previously, it was not possible to investigate time-resolved SnRK2 activity in living plant cells," said Biological Sciences Distinguished Professor Julian Schroeder, a member of the Section of Cell and Developmental Biology and senior author of the new paper. "The SNACS sensor reports direct real-time visualization of SnRK2 kinase activity in single live plant cells or tissues."

The new biosensor is already paying dividends. The researchers describe using SNACS to provide new evidence about longstanding questions about SnRK2 and foundational interactions with carbon dioxide. The researchers show that abscisic acid, a drought stress hormone in plants, activates the kinases, but that elevated carbon dioxide does not, resolving a recently debated question.

"Our findings could benefit researchers investigating environmental stress responses in plants and analyzing how different signaling pathways interact with one another in plant cells," said Yohei Takahashi, a UC San Diego project scientist and co-corresponding author of the study. "The ability to investigate time-resolved SnRK2 kinase regulation in live plants is of particular importance for understanding environmental stress responses of plant cells."

The new nanosensor was developed using an approach pioneered by the late UC San Diego Professor Roger Tsien, in part for which he was awarded a Nobel Prize.

A paper recently published online in the journal Chest reports on a study of the palliative ventilator withdrawal (PVW) procedure performed in intensive care units (ICU) at end of life. The study's goal was to determine the level of distress patients experience and identify treatments that could bring relief. Findings show that up to one-third of PVW patients experience an episode of rapid breathing called tachypnea as a marker of distress, and administration of opiates before PVW could help with symptom control. Corey Fehnel, M.D., M.P.H., a palliative care researcher in the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, and Assistant Professor of Neurology at Harvard Medical School, is lead author on the paper.

On average, nearly one in five Americans will die in an ICU each year, and many of these deaths occur after the decision has been made to extubate and move from curative- to comfort-focused care. Although numerous professional societies and patient groups have advocated for improved management of ventilated ICU patients transitioning to palliative care, the process of PVW and the discomfort that patients experience has remained understudied. As a result, the practice varies widely across ICUs, and little is known about the indicators of patient distress and how to better control symptoms.

Monitoring symptoms of distress among hospitalized COVID-19 patients at end of life presents even more of a challenge. COVID-19 patients who are intubated on mechanical ventilation require providers to observe special aerosolized droplet isolation precautions. They must wear N95 masks, face shields, hats, gowns, and run HEPA filters in the room when opening the "circuit" to the ventilator or performing procedures, including extubation. These precautions make it difficult for critically ill patients to use non-verbal cues as a means of communication with their care providers.

In addition, patients are physically isolated with similar patients, and providers try to limit the number of times they enter the patient's room to prevent transmission of the virus. But most importantly, families are not allowed in the hospital to be with these patients during extubation, and they are an important part of easing patient distress and assuring patient comfort at end of life. Taken all together, the combined effect is a perfect storm of barriers to effective symptom assessment for these patients.

"We fervently hope that all patients will be comfortable at end of life in the ICU but unfortunately some people experience discomfort, and we identified one tactic to alleviate that distress," said Dr. Fehnel. "The results of this study, which point to administration of opiates before PVW and in anticipation of distress, could help with symptom control and can be readily applied to COVID-19 and all critically ill patients during this time of great need."