Brain

The remote learning experience of parents who had their children at home in Spring 2020, as schools across the US closed during the United States' COVID-19 lockdown, was more positive than widely believed.

That is the suggestion from a new study published in the Journal of School Choice, which looked at the experience of a nationally representative sample of 1,700 parents stretching right across America.

On average only 44% of parents reported the online learning program required too much of parents, while 38% of parents said it was difficult for them to manage the online provisions.

However, worryingly, most parents (63%) believed remote learning caused their child to fall behind.

While the study focused on 3,414 children's parents' experiences, the results revealed to the experts from the University of Colorado, at Colorado Springs, a broad picture of the provision different types of schools offered too.

These findings show more than 80% of schools provided some type of remote learning after closing because of the pandemic. Parents generally rated the programs as effective and the resources as helpful, however most (67%) characterized their engagement as heavily involved daily.

Almost 30% of the time mothers and fathers managed the responsibility equally. Parents spent about 2.5 hours per day helping with schoolwork; children spent about an hour more each day in remote learning.

82% of participants reported their schools eventually developed some type of remote learning. 10% reported schools cancelled classes and provided no remote learning, with the remainder resuming or continuing classes until the end of the school year.

For families in schools cancelling classes and providing no resources, most students (49%) spent their time primarily watching TV and playing games. Only 28% engaged in a learning program created by parents. The remainder worked around the house, worked for pay, or pursued other interests.

Results were not, however, uniform across school type. According to parents, private schools frequently appeared to be the most responsive, engaged, and innovative, followed by charters and then traditional public schools.

Also contrary to predictions throughout summer 2020 about parents' school choices for Fall 2020, only a small percentage of survey respondents said they were going to homeschool in the new school year. However, more than a third planned to send their child to a virtual school. Of those who were not going to send their children to brick and mortar schools, concern about their child's health was the dominant and predictable motivation.

"This suggests if there was going to be a significant shift in the education sector, it would be to virtual schools rather than homeschooling," said the study's lead author, Dr Dick Carpenter, "and the shift would likely be temporary, assuming COVID-19 is mitigated."

The study results, although specific only to Spring 2020, provide important information about remote learning in the future.

"Schools rated as most effective were those that more often chose to communicate with students, create real-time, online programs, and set higher expectations," described Dr Carpenter.

The survey featured 44 mostly closed-ended questions about the resources families had during at-home schooling, how children spent their day, how much time was spent on schoolwork, communication with school, assessment of the experience, plans for the 2021 school year, and basic demographics.

Correspondents were spread across various schools - public (84%), private (10%), and charter (6%).

Hopefully, as remote learning continues in schools internationally, officials can apply these findings "to offer the most effective learning possible to students," report co-author, Dr Joshua Dunn, also a professor at UCCS, says.

"Despite the better-than-expected experience in the spring, many parents we surveyed were still concerned about their child's academic future because of school closures. Schools need to apply lessons learned from this study to provide the best and most equitable remote learning possible under circumstances like this," Dunn concluded.

The majority of survey correspondents were white females. More than 50% held at least a college degree. Slightly more than 60% reported household incomes of greater than $50,000. Additionally, respondents' mean age was 39 and the mean number of children per respondent was two.

Almost 76% of respondents were married. A little more than half of respondents were working full time when data were collected. The next largest percentage (18%) classified themselves as homemakers. A little more than 60% of their spouses were working full time. Equal percentages of respondents and spouses were working part-time.

With this in mind, the study therefore has a slight limitation with the sample "perhaps skewing more toward women and people who have higher education levels completing the survey," the authors state.

"Moreover, by necessity, parents were instructed to answer questions thinking of their youngest child in a certain school type. This may result in responses more representative of children in younger grade levels," they add.

CLEVELAND--The combined effectiveness of three COVID-prevention strategies on college campuses--mask-wearing, social distancing, and routine testing--are as effective in preventing coronavirus infections as the Pfizer and Moderna vaccines approved by the U.S. Food and Drug Administration (FDA), according to a new study co-authored by a Case Western Reserve University researcher.

The research, published in Annals of Internal Medicine, has immediate significance as college semesters are poised to start again--and as the distribution of approved vaccines lags behind goals.

The study found that a combination of just two common measures--distancing and mandatory masks--prevents 87% of campus COVID-19 infections and costs only $170 per infection prevented.

Adding routine lab-based testing to the mix would prevent 92% to 96% of COVID infections. Still, the cost per infection prevented increases substantially, to $2,000 to $17,000 each, depending on test frequency.

As the infection rate continues to rise during the winter, the findings are especially meaningful for institutions of higher learning aiming to strike a balance between in-person and remote instruction, while managing costs to promote safety and reduce transmissions.

"While some measures are highly effective, implementing them is entirely up to each college's financial situation, which may have already become strained because of the pandemic," said Pooyan Kazemian, co-senior author of the study and an assistant professor of operations at the Weatherhead School of Management at Case Western Reserve.

"It is clear that two common non-medical strategies are very effective and inexpensive--and allow for some in-person instruction," said Kazemian. "While it's true routine testing of the asymptomatic helps catch some infections early and reduce transmissions, they also pose the highest financial and operational burden, even if performed every 14 days."

Among the study's other findings:

About three of every four students--and nearly one in six faculty--would become infected over the semester in the absence of all mitigation efforts.
Minimal social distancing policies would only reduce infections by 16% in students.

While closing the campus and switching to online-only education would reduce infections by 63% among students, it would be less effective than opening the campus and implementing a mask-wearing and social distancing policy, which would reduce infections by 87% among students.

The study

Researchers examined 24 combinations of four common preventive strategies--social distancing, mask-wearing, testing and isolation--and calculated their effectiveness and cost per infection prevented.

The team took into account interactions between three groups: students, faculty, and the surrounding community (including staff), and used a computer simulation model Kazemian and his colleagues developed--known as Clinical and Economic Analysis of COVID-19 interventions, or CEACOV--that simulated a semester of a mid-sized college (5,000 students and 1,000 faculty).

"While states have started offering COVID-19 vaccine to healthcare workers, first responders, and long-term care facilities, it is unlikely that most students and university faculty and staff will be offered a vaccine until late in the spring semester," said Kazemian. "Therefore, commitment to mask-wearing and extensive social distancing, including canceling large gatherings and reducing class sizes with a hybrid education system, remains the primary strategy for minimizing infections and keeping the campus open during the spring semester."

New research has found as climate change causes the world's oceans to warm, baby sharks are born smaller, exhausted, undernourished and into environments that are already difficult for them to survive in.

Lead author of the study Carolyn Wheeler is a PhD candidate at the ARC Centre of Excellence for Coral Reef Studies at James Cook University (Coral CoE at JCU) and the University of Massachusetts. She examined the effects of increased temperatures on the growth, development and physiological performance of epaulette sharks--an egg-laying species found only on the Great Barrier Reef. She and her team studied the sharks as embryos and as hatchlings.

"We tested shark embryos in waters up to 31°C," Ms Wheeler said.

"The hotter the conditions, the faster everything happened, which could be a problem for the sharks. The embryos grew faster and used their yolk sac quicker, which is their only source of food as they develop in the egg case. This led to them hatching earlier than usual."

This meant hatchlings were not only smaller, they needed to feed almost straight away--while lacking significant energy.

Co-author Associate Professor Jodie Rummer, also from Coral CoE at JCU, says the waters of the Great Barrier Reef will likely experience summer averages close to or even in excess of 31°C by the end of the century.

Since sharks don't care for their eggs after they are laid, a shark egg must be able to survive unprotected for up to four months. Dr Rummer flags rising ocean temperatures as a major concern for the future of all sharks--both egg-laying and live-bearing species.

"The epaulette shark is known for its resilience to change, even to ocean acidification," Dr Rummer said. "So, if this species can't cope with warming waters then how will other, less tolerant species fare?" she said.

Sharks and the class of animals they belong to, which includes rays and skates, are slow growing. They also don't reproduce that often compared to other fishes. The populations of these creatures are already threatened across the globe.

The study suggests the sharks of the future will be born--or hatch, in this case--not only at a disadvantage but into environments that are already at the warmest they can tolerate.

"The study presents a worrying future given that sharks are already threatened," Ms Wheeler said.

"Sharks are important predators that keep ocean ecosystems healthy. Without predators, whole ecosystems can collapse, which is why we need to keep studying and protecting these creatures."

"Our future ecosystems depend us taking urgent action to limit climate change," Dr Rummer said.

Curtin University researchers have used ancient crystals from eroded rocks found in stream sediments in Greenland to successfully test the theory that portions of Earth's ancient crust acted as 'seeds' from which later generations of crust grew.

The findings not only advance an understanding of the production of the Earth's crust through deep time, along with its structure and composition, but reveal a planet-wide crustal growth spurt three billion years ago when mantle temperatures peaked.

Lead author Professor Chris Kirkland, from Curtin University's Timescales of Mineral Systems Group, said the research used the chemistry of old crystals preserved within stream sediments in arctic Greenland to test the idea that portions of ancient crust served as seeds for later growth of continents.

"We found there was a widespread bloom in crust production three billion years ago, during a peak in mantle temperatures," Professor Kirkland said.

"Three-billion-year-old magmas from the mantle had penetrated even more ancient four-billion-year-old crust to create rocks of mixed composition.

"Old crust appeared to be critical in continent production as it acted much like a life raft to preserve crust through later stages of earth history.

"The spike in the age of crust production in Greenland matches other regions across the globe and points to a significant widespread event that formed crust relatively early in the history of our planet."

Professor Kirkland said understanding the production of crust improved the understanding of its structure and composition.

"The Earth's crust hosts concentrations of economically valuable ores and minerals but finding them is becoming increasingly challenging as more near-surface deposits are exhausted," Professor Kirkland said.

"Understanding that later crust is 'seeded' on older pre-existing crust refines our understanding of the generation of where certain metals are hosted and ultimately explains the habitable part of our planet."

To properly monitor and help curb the spread of COVID-19, several millions of diagnostic tests are required daily in just the United States alone. There is still a widespread lack of COVID-19 testing in the U.S. and many of the clinical diagnostics protocols require extensive human labor and materials that could face supply shortages and present biosafety concerns.

The current gold standard for COVID-19 diagnostic testing in the U.S., developed by the U.S. Centers for Disease Control and Prevention (CDC), is quantitative PCR-based (qPCR) molecular tests that detect the presence of the viral nucleic acid. Although highly accurate, these CDC-approved tests require specialized reagents, equipment, and personnel training. In addition, multiple diagnostic kits that have been rapidly developed and introduced into the market have accuracy, cost and distribution limitations. Moreover, the test systems currently utilized are not easily scalable to a high-throughput platform to deliver the required millions of tests per day.

Given the urgent need to develop alternative reagents and approaches to provide nucleic-acid testing in the face of heightened demand and potential shortages, a research team from Florida Atlantic University's Schmidt College of Medicine has developed a simplified COVID-19 testing protocol that offers a distinct advantage over the standard viral or universal transport medium (VTM). This testing protocol can detect minimal quantities of the SARS-CoV-2 using samples from both upper respiratory tract swabs (nasal and throat) as well as saliva, and can be used in research laboratories with minimal molecular biology equipment and expertise.

The protocol, published in PLOS ONE, utilizes TRIzol (guanidinium thiocyanate/phenol-chloroform) to purify the viral RNA from different types of clinical specimens, requires minimal biosafety level precautions and, given its high sensitivity, can be easily adapted to pooling samples strategies. Using this simplified protocol, samples are eluted in TRIzol immediately after collection and RNA is extracted. Results have shown that this protocol is as efficient, if not more than the CDC-approved silica-membrane based RNA purification microcolumns in isolating small amounts of viral and cellular RNA from multiple types of samples (nasal and throat swabs and saliva).

"The high sensitivity of our protocol may be useful in testing patients with low viral titers such as asymptomatic patients or testing individuals prior to quarantine release. Our method also enables several patient samples to be pooled, decreasing the number of tests required for larger populations," said Massimo Caputi, Ph.D., lead author and a professor of biomedical science in FAU's Schmidt College of Medicine. "In addition, testing can easily be carried out by any research laboratory equipped with minimal standard equipment. Since saliva can be utilized as a reliable source of virus, samples can be self-obtained by patients and inactivated in TRIzol, eliminating the need for medical staff and higher-level biosafety protocols and facilities."

With this new approach, samples are first pooled and tested; positive pools are then retested individually. This relatively simple solution decreases the testing resources used but results in a loss in sensitivity from diluting positive patient samples with negative ones, hence the need of highly-sensitive tests that utilize biological materials, like saliva, which can be obtained in larger amounts and can be easily preserved for re-testing.

The protocol uses common chemical reagents that are in abundant supply and can isolate high-quality RNA that can be utilized for multiple assays and RNA sequencing projects. In addition, samples in TRIzol can be preserved at 4 C for more than a week with minimal degradation and little to no loss of viral RNA. Moreover, the ability to use saliva samples, which are as- or more sensitive and reliable than nasopharyngeal swabs, offers an attractive specimen alternative. Nose and throat swabs are the most common upper respiratory tract specimens used for COVID-19 diagnostic testing. However, the collection of these specimen types can cause discomfort, bleeding, and requires close contact between healthcare workers and patients, posing the risk of transmission.

In the most commonly used COVID-19 testing protocols, a healthcare provider collects a nasal or throat swab and transfers it to a vial containing a few milliliters of VTM. The sample is then transported to a laboratory for testing. The transport and storage can take from a few hours to a few days depending on the distance and processing times of the nearest clinical laboratory. The CDC recommends that specimens are stored at 2 to 8 C for up to 72 hours after collection and at -70 C or lower for longer periods of time. However, the logistics of having multiple sample collection points, chokeholds in the reagents supply chain, and abrupt increases in the demand for testing due to local outbreaks might generate unexpected delays in processing the samples.

"We can expect a high demand for COVID-19 testing in the foreseeable future as testing of the general population and asymptomatic individuals becomes more widespread," said Janet Robishaw, Ph.D., co-author, senior associate dean for research and chair of the Department of Biomedical Science in FAU's Schmidt College of Medicine. "The lack of control of the pandemic in many underdeveloped countries as well as the continued escalation of COVID-19 in the U.S. also are compelling reasons to increase testing efforts. We are hopeful that a combination of testing approaches, including protocols like ours, may be the most efficient way to fill the current and future gaps in testing."

To resolve the energy crisis and environmental issues, research to move away from fossil fuels and convert to eco-friendly and sustainable hydrogen energy is well underway around the world. Recently, a team of researchers at POSTECH has proposed a way to efficiently produce hydrogen fuel via water-electrolysis using inexpensive and readily available nickel as an electrocatalyst, greenlighting the era of hydrogen economy.

A POSTECH research team led by Professor Jong Kyu Kim and Ph.D. candidate Jaerim Kim of the Department of Materials Science and Engineering and a team led by Professor Jeong Woo Han and Ph.D. candidate Hyeonjung Jung of the Department of Chemical Engineering have jointly developed a highly efficient nickel-based catalyst system doped with oxophilic transition metal atoms and have identified the correlation between catalytic adsorption properties and hydrogen evolution reaction (HER) kinetics in alkaline medium. Recognized for their significance, these research findings were featured as the front cover paper for the Journal of the American Chemical Society.

Fuel cell is an eco-friendly power generating device that produces electricity using a chemical reaction in which oxygen (O?) and hydrogen (H?) produce water (H?O). During this process, water electrolysis reduction occurs as a counter-reaction, which dissociates water to generate hydrogen fuel. This is known to be the most environmentally-safe and sustainable way to produce high-purity hydrogen fuel in large quantities. However, it has a downside of being costly and inefficient since it requires the use of precious metals as electrodes. In order to reduce the unit cost of hydrogen fuel produced through water-electrolysis, it is paramount to develop highly active, stable, and inexpensive electrochemical catalyst, capable of maximizing the hydrogen production performance.

To this, the joint research team designed a highly effective catalyst by combining earth-abundant nickel with a series of oxophilic transition metal elements to optimize the adsorption abilities in alkaline HER. The team further demonstrated that the incorporation of oxophilic dopants can effectively control the adsorption properties of the surface of Ni-based catalysts.

In order to further enhance the HER activity of the Ni-based catalysts, the researchers introduced a unique 3-dimentional (3D) nanohelix (NH) array, easily fabricated by an oblique-angle codeposition method, for abundant surface active sites, efficient pathways for charge transfer, and open channels for mass transport. They had successfully fabricated highly active and stable Cr-incorporated Ni NHs catalyst showing an excellent hydrogen production efficiency with reduced overvoltage more than four times compared to the conventional nickel-based thin film catalysts.

"This research is significant in that it provides the scholarly foundation for high performance and commercialization of sustainable hydrogen energy conversion system," explained Professor Jong Kyu Kim, the corresponding author of the paper. "The core concepts of the design strategy and experimental methodology for efficient bimetallic electrocatalysts can be applied not only to water electrolysers, but also to fuel cells, carbon dioxide reduction, and photo-electrochemical system. It is anticipated that securing this original technology will have significant ripple effects and technological expansion in the environmental energy sector."

Professor Jeong Woo Han, the co-corresponding author of the paper, added, "Computational chemistry has dramatically accelerated the water electrolysis reaction by quickly finding bimetals that can control the catalyst adsorption strength to enable the fabrication of bimetallic electrocatalysts using only nonprecious materials."

COLUMBIA, Mo. - As a former school nurse in the Columbia Public Schools, Gretchen Carlisle would often interact with students with disabilities who took various medications or had seizures throughout the day. At some schools, the special education teacher would bring in dogs, guinea pigs and fish as a reward for good behavior, and Carlisle noticed what a calming presence the pets seemed to be for the students with disabilities.

Now a research scientist at the MU Research Center for Human-Animal Interaction (ReCHAI) in the MU College of Veterinary Medicine, Carlisle studies the benefits that companion animals can have on families. While there is plenty of existing research emphasizing the benefits of dogs for children with autism, Carlisle's newest study has found cats may help increase empathy while decreasing separation anxiety for children with autism. The findings can have beneficial implications for families considering adopting a companion animal for their child.

"Previous research has shown parents of kids with autism are more stressed than parents of kids with any other disability," Carlisle said. "If a family is considering adopting a companion animal, we want to provide the best evidence-based information possible so they can make an informed decision, and cats might be more beneficial than dogs to some families."

In the study, families that had children with autism aged 6-14 were recruited through the MU Thompson Center for Autism and Neurodevelopmental Disorders and monitored after adopting a cat into their home. The cats were screened for temperament to ensure they were calm and a good match for the family. Not only did the families report an instant bond between their child with autism and their new cat, but the bond remained strong over the course of time, and the child's anxiety decreased over time.

"We found the main benefit of these companion animals is their unconditional acceptance," Carlisle said. "Some children with autism may have sensory issues or be sensitive to loud noises, so a cat may be an appropriate, comforting pet for some families due to their calming presence."

Helping families make the best choice for their kids has motivated Carlisle's research with companion animals, and the study's findings highlight the benefits of human-animal interaction.

"As a former pediatric nurse, I have always strived to help children, and one thing I learned is that you need to involve the parents so they can make informed choices for their children," Carlisle said. "I see pets as a way to enhance wellness, and it feels gratifying to provide assistance to families that have a lot on their plate."

A team of HIV researchers, cellular biologists, and biophysicists who banded together to support COVID-19 science determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells. The structural map - which is now published in the journal PNAS, but has been open-access for the scientific community since August - has laid the groundwork for new antiviral treatments tailored specifically to SARS-CoV-2, and enabled further investigations into how the newly emerged virus ravages the human body.

"Using X-ray crystallography, we built an atomic model of ORF8, and it highlighted two unique regions: one that is only present in SARS-CoV-2 and its immediate bat ancestor, and one that is absent from any other coronavirus," said lead author James Hurley, a UC Berkeley professor and former faculty scientist at Lawrence Berkeley National Laboratory (Berkeley Lab). "These regions stabilize the protein - which is a secreted protein, not bound to the membrane like the virus's characteristic spike proteins - and create new intermolecular interfaces. We, and others in the research community, believe these interfaces are involved in reactions that somehow make SARS-CoV-2 more pathogenic than the strains it evolved from."

Structural biology in the spotlight

Generating protein structure maps is always labor intensive, as scientists have to engineer bacteria that can pump out large quantities of the molecule, manipulate the molecules into a pure crystalline form, and then take many, many X-ray diffraction images of the crystals. These images - produced as X-ray beams bounce off atoms in the crystals and pass through gaps in the lattice, generating a pattern of spots - are combined and analyzed via special software to determine the location of every individual atom. This painstaking process can take years, depending on the complexity of the protein.

For many proteins, the process of building a map is helped along by comparing the unsolved molecule's structure to other proteins with similar amino acid sequences that have already been mapped, allowing scientists to make informed guesses about how the protein folds into its 3D shape.

But for ORF8, the team had to start from scratch. ORF8's amino acid sequence is so unlike any other protein that scientists had no reference for its overall shape, and it is the 3D shape of a protein that determines its function.

Hurley and his UC Berkeley colleagues, experienced in structural analysis of HIV proteins, worked with Marc Allaire, a biophysicist and crystallography expert at the Berkeley Center for Structural Biology, located at Berkeley Lab's Advanced Light Source (ALS). Together, the team worked in overdrive for six months - Hurley's lab generated crystal samples and passed them to Allaire, who would use the ALS's X-ray beamlines to take the diffraction images. It took hundreds of crystals with multiple versions of the protein and thousands of diffraction images analyzed by special computer algorithms to puzzle together ORF8's structure.

"Coronaviruses mutate differently than viruses like influenza or HIV, which quickly accumulate many little changes through a process called hypermutation. In coronaviruses, big chunks of nucleic acids sometimes move around through recombination," explained Hurley. When this happens, big, new regions of proteins can appear. Genetic analyses conducted very early in the SARS-CoV-2 pandemic revealed that this new strain had evolved from a coronavirus that infects bats, and that a significant recombination mutation had occurred in the area of the genome that codes for a protein, called ORF7, found in many coronaviruses. The new form of ORF7, named ORF8, quickly gained the attention of virologists and epidemiologists because significant genetic divergence events like the one seen for ORF8 are often the cause of a new strain's virulence.

"Basically, this mutation caused the protein to double in size, and the stuff that doubled was not related to any known fold," added Hurley. "There's a core of about half of it that's related to a known fold type in a solved structure from earlier coronaviruses, but the other half was completely new."

Answering the call

Like so many scientists working on COVID-19 research, Hurley and his colleagues opted to share their findings before the data could be published in a peer-reviewed journal, allowing others to begin impactful follow-up studies months earlier than the traditional publication process would have allowed. As Allaire explained, the all-hands-on-deck crisis caused by the pandemic shifted everyone in the research community into a pragmatic mindset. Rather than worrying about who accomplished something first, or sticking to the confines of their specific areas of study, scientists shared data early and often, and took on new projects when they had the resources and expertise needed.

In this case, Hurley's UC Berkeley co-authors had the viral protein and crystallography expertise, and Allaire, a longtime collaborator, was right up the hill, also with crystallography expertise and, critically, a beamline that was still operational. The ALS had received special funding from the CARES Act to remain operational for COVID-19 investigations. The team knew from reviewing the SARS-CoV-2 genomic analysis posted in January that ORF8 was an important piece of the (then much hazier) pandemic puzzle, so they set to work.

The authors have since all moved on to other projects, satisfied that they laid the groundwork for other groups to study ORF8 in more detail. (Currently, there are several investigations underway focused on how ORF8 interacts with cell receptors and how it interacts with antibodies, as infected individuals appear to produce antibodies that bind to ORF8 in addition to antibodies specific to the virus's surface proteins.)

"When we started this, other projects had been put on hold, and we had this unique opportunity to hunker down and solve an urgent problem," said Allaire, who is part of Berkeley Lab's Molecular Biophysics and Integrated Bioimaging Division. "We worked very closely, with a lot of back and forth, until we got it right. It really has been one of the best collaborations of my career."

As schools prepare to re-open to all pupils in February, experts warn that UK government plans for mass testing risks spreading covid-19 more widely.

Writing in The BMJ, Professor Jon Deeks and colleagues at the Royal Statistical Society argue that using the INNOVA rapid lateral flow tests to manage classroom outbreaks, without isolating close contacts, risks increasing disease spread and causing further disruption to children's education.

Before Christmas, schools limited pupil mixing and activities, and isolated pupil groups at home once a covid-19 case was identified, they explain. This year the government is relying on the INNOVA rapid lateral flow tests to mass screen staff and pupils, and test close contacts of confirmed covid cases.

Under this "serial-testing" strategy, close contacts remain in school, are tested daily for seven days, and are only sent home if they test positive.

But scientists are concerned that negative Innova results are too inaccurate to rule out COVID, warn Deeks and colleagues. For example, the MHRA authorisation for INNOVA excludes using negative results to "enable activity", and the Chief Medical Officer, World Health Organization, Royal College of Pathologists, SAGE, and others have likewise advised caution.

"There is a real risk that the serial-testing strategy of contacts may increase rather than decrease COVID cases in schools," they warn.

They point out that in six studies of people with symptoms, INNOVA identified 58 to 96% of cases compared with the "gold standard" PCR test, and test performance declined when not done by experts, as will happen in schools.

But pupils tested in schools will not have symptoms and three studies in symptomless people show the test performing worse, they add.

While mass testing with INNOVA will detect some of these cases, it will miss many, and falsely reassure those testing negative if they are not properly informed of the test's limitations, they argue.

They warn that if any of the pupils who test negative are infected, they risk becoming infectious and spreading the virus before testing positive and isolating, and that any clinically vulnerable pupils or staff in the class will be put at particularly high risk.

"This proposed strategy is, in effect, using negative INNOVA results to enable pupils to remain in school contrary to the MHRA restriction and scientific advice," they write.

They call for rigorous evaluation of the new strategy compared with other testing options, such as the use of PCR test-to-release after 5 days (as required for travellers), to check whether each strategy's benefits outweigh its harm, particularly with the increased transmission risk of the new variant.

They acknowledge that home isolation has a hard impact on children, families, and teachers, but say "if INNOVA testing in schools risks spreading the disease more widely, it may lead to even more disruption to education and put many more people at risk."

Fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in African Americans and maternal fetal genotype discordance is also associated with this risk.

Preeclampsia, characterized by increased blood pressure after 20 weeks of pregnancy, as well as other abnormalities (e.g., protein in the urine), is dangerous to mothers and their infants. Previous studies found that individuals with African ancestry may carry APOL1 genetic variants that increase risk for chronic kidney disease. This study published in the American Journal of Kidney Diseases (AJKD) found that fetal high-risk APOL1 genotypes and maternal-fetal APOL1 genotype discordance independently contribute to preeclampsia risk in African-American mothers. This association was not observed in Haitian mother-infant pairs possibly because of different environmental exposures and cultural milieu. Additional studies are required to understand why APOL1 associations with preeclampsia differ by maternal country of origin and to improve management of mothers at risk for preeclampsia.

Women who use marijuana could have a more difficult time conceiving a child than women who do not use marijuana, suggests a study by researchers at the National Institutes of Health. Marijuana use among the women's partners--which could have influenced conception rates--was not studied. The researchers were led by Sunni L. Mumford, Ph.D., of the Epidemiology Branch in NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development. The study appears in Human Reproduction.

The women were part of a larger group trying to conceive after one or two prior miscarriages. Women who said they used cannabis products--marijuana or hashish--in the weeks before pregnancy, or who had positive urine tests for cannabis use, were around 40% less likely to conceive per monthly cycle than women who did not use cannabis. The authors noted that although the findings suggest cannabis could affect women's fertility, they should be tempered with caution as the study observed a relatively small number of cannabis users. However, the authors say their results suggest that women trying to conceive should exercise caution with cannabis use until more definitive evidence is available.

The researchers analyzed data from a broader study of more than 1,200 women ages 18 to 40 with one or two pregnancy losses. The women participated in the study for up to six monthly cycles while attempting pregnancy and throughout pregnancy if conception occurred. After enrolling in the study, the women responded to a questionnaire asking if they had used marijuana, pot, or hashish in the past 12 months, with responses ranging from never, rarely, occasionally, sometimes, often, to daily. Each woman also provided urine samples for analysis when they first entered the study and after six months if they did not conceive or at the time of positive pregnancy test if they conceived.

A total of 62 women (5%) either had a positive urine test or responded that they had used cannabis before conception.

For each monthly cycle, women who had used cannabis while trying to conceive were 41% less likely to conceive than non-users. Similarly, a smaller proportion of cannabis users than non-users became pregnant during the study--42% versus 66%. The authors found no differences in miscarriage rates between users and non-users who had achieved pregnancy.

The authors noted that, compared to non-users, cannabis users also had differences in reproductive hormones involved in ovulation. These differences could potentially have influenced their likelihood of conception. Specifically, users had higher levels of luteinizing hormone and a higher proportion of luteinizing hormone to follicle stimulating hormone.

The authors also noted that animal studies had found that cannabis use could alter the lining of the uterus, making it less likely an embryo to implant and establish a pregnancy. Until more information is available, the authors said, women trying to become pregnant should be aware that cannabis could potentially affect their pregnancy chances.

COVID-19 infections are once again rising at an alarming rate in San Francisco's Latinx community, predominantly among low-income essential workers, according to results of a massive community-based testing blitz conducted before and after the Thanksgiving holiday by Unidos En Salud -- a volunteer-led partnership between the Latino Task Force for COVID-19 (LTF), UC San Francisco , the Chan Zuckerberg Biohub (CZ Biohub), and the San Francisco Department of Public Health (SFDPH).

Unidos En Salud launched their "Healthy Holidays" initiative the weekend before Thanksgiving (Nov. 22-24) in San Francisco's Mission District, where they have been perfecting their community-based surveillance testing and response program and solidifying relationships with community members through the LTF since April. The initiative then expanded testing after the holiday (Nov. 29-Dec. 1) to three additional highly impacted neighborhoods -- the Bayview, Excelsior, and Tenderloin.

"Cases have been surging for weeks, and it was clear that the holiday season this year was going to present a high risk for accelerating the spread of the virus," said UCSF infectious disease expert Diane Havlir, MD, co-Founder of the Unidos En Salud initiative, who presented initial findings to LTF community partners on December 7, 2020. "Rather than wait and see what would happen, UCSF and the Latino Task Force decided to respond proactively with a surge of our own, in partnership with DPH, focused on the communities where we knew the hammer was going to fall hardest."

"As the region enters a renewed phase of lockdown, these results are a reminder the brunt of this disease is still being felt by Latinos and people without the economic privilege to easily shelter in place. Because existing disparities, it is often those with the least who are being hurt the most, people who are often working multiple jobs just to make rent and keep food on the table for themselves and family," said LTF Health Committee Chair, Jon Jacobo, one of the initiative's organizers. "If we truly want to turn this pandemic around, we need to fundamentally change how we are addressing the pandemic and how we are supporting the most vulnerable among us."

Findings Show Continued Outsize Impact on Latinx Community, Ongoing Asymptomatic Spread

Following six days of intensive and strategic door-to-door community canvassing by LTF volunteers -- which focused on census tracts with the highest number of cases according to SFDPH data -- the Healthy Holidays initiative ultimately tested more than 6800 people before and after the Thanksgiving holiday.

Organizers reported a test positivity rate of 4.4 percent across the initiative's four post-holiday test sites, exceeding the city's 2.9% 7-day average during the current surge, as of December 9.  Although just over half of those tested were Latinx, a disproportionate 79 percent of positive results came from the Latinx community. At the Mission test site at 24^th St. BART Plaza, where overall cases were highest, one in ten Latinx individuals tested positive for the virus. Infection rates were also particularly high among low-income workers, including food and beverage workers and day laborers, as well as among people with indigenous backgrounds, particularly from Mexico and Central America.

The initiative found that about a third of infected individuals were asymptomatic at the time of testing and more than half were unaware of having been exposed to the virus, emphasizing the need for continued vigilance in combating a disease that can spread rapidly without detection.

"These ongoing partnerships for prevalence studies in high-impacted communities continue to inform local health strategy and policies," said Dr. Grant Colfax, Director of the San Francisco Department of Public Health. "The information and data gathered help guide not only health policy but the city's overall approach to supporting communities disproportionately impacted by this virus."

Rapid Antigen Tests Enabled Results, Quarantine and Support Within Hours

Unidos En Salud previously conducted one of the first field tests of the BinaxNOW rapid antigen test, manufactured by Abbott, in a community setting at their September testing pop-up at the 16^th and Mission BART Plaza. Collaborators at CLIAhub, the joint UCSF/CZ Biohub COVID diagnostic laboratory that has provided test analysis for all of the group's initiatives, compared BinaxNOW results to PCR results from the same individuals and found the rapid test to be extremely reliable at identifying infected individuals during the most infectious phase of the disease.

In the much larger holiday testing event, the group put the BinaxNOW tests to use for the first time as a proof-of-concept of their potential usefulness in broader surveillance testing efforts. As in September, individuals at the group's Mission District test site gave two nasal swabs, one to be sent for standard PCR analysis at CLIAhub, and the second inserted on site into a BinaxNOW card, which is similar to a pregnancy test, providing results within 15 minutes. The speed of the results allowed team members to notify those who tested positive within hours rather than days, and to provide on-site counseling and support for immediate quarantine. The rapid results also allowed SFDPH to quickly initiate contact tracing.

Comparison to PCR results from the same individuals, completed 24 to 48 hours later, showed the tests had accurately identified more than 99 percent of individuals considered to be highly contagious. The researchers also found the tests to perform well in children, contrary to recent reports.

The CLIAhub and Unidos En Salud teams published their analysis of the performance characteristics of the BinaxNow rapid tests in symptomatic and asymptomatic individuals in this community setting January 4, 2021 in the Journal of Infectious Disease. The study's corresponding author is CLIAhub director Joe DeRisi, PhD, who is co-president of the Chan Zuckerberg Biohub, a UCSF professor of biochemistry and Howard Hughes Medical Institute investigator.

Community Wellness Teams, Home Visits Connect People with Resources to Isolate

For all who tested positive, whether on PCR or rapid tests, LTF Community Wellness Team members followed up to connect infected individuals to support for successful quarantine, including food, cleaning supplies and referrals to resources such as city-funded isolation and quarantine hotels.

"The LTF Community Wellness Teams are unique compared to the traditional test and contract trace approach," said Valerie Tulier-Laiwa, Coordinator of the LTF.  "This additional support from our Community Wellness Teams is essential to make isolation and quarantine successful and stop the spread of the virus among Latinx and low-income people."

The initiative also complemented SFDPH contact tracing with a follow-up home testing program for infected individuals living in large households, connecting as many as possible with resources for effective isolation through LTF's Community Wellness Teams.

"Community members I spoke with at the testing site who tested positive on rapid tests were eager to get close contacts tested out of a sense of responsibility for protecting loved ones, coworkers, and the larger community," said UCSF infectious disease clinical fellow Luis Rubio, MD, who was part of the initiative's clinical response team.

Volunteers provided rapid and PCR-based testing to household members within a day of the initial positive result and then again after a week. These visits included a trusted community health worker who could answer questions and give households specific guidance on how to safely isolate.

"Having rapid COVID-19 test results and dedicated time and space for household contacts to ask the community health worker questions was very much appreciated by families and we hope these services will support people in large households to effectively isolate and quarantine and decrease transmission," said UCSF infectious disease specialist Carina Marquez, MD, who led the household testing program.

To Halt Pandemic: Low-Barrier Community-Based Testing and Rapid Response

Unidos En Salud organizers, who have now provided free COVID-19 testing to 14,000 people since April through their regular weekly and larger pop-up initiatives, believe the community-based test-and-respond approach they have developed in their work in the Mission District could be a model for more effectively controlling the virus amidst the current frightening surge.

"We need to be making it as easy as possible for everyone in communities most affected by the virus to get tested regularly, symptoms or no, and to get people who test positive into isolation as quickly as possible with supportive services to cut off the chain of transmission. This approach will continue to be critical as the new vaccines become available," said Havlir, who is chief of the UCSF Division of HIV, Infectious Diseases and Global Medicine.

To reach as many people in affected communities as possible, regardless of symptoms or resources, the group's low-barrier testing is not only free, but requires no reservations, no health insurance, and no identification -- anyone can walk up and get tested. It is also community based and staffed -- located at convenient public transit hubs and community centers in the most affected neighborhoods, and organized, staffed and operated by members of the community being served.

"A critical component of our success is the many volunteers from the community who are involved in initial canvassing, coordinating testing onsite and the Community Wellness Teams that follow up with people who test positive," Jacobo said. "This has let us provide wrap-around services that are tailored to the need of each patient but are also culturally competent, and all are built upon the trust we have been building through our deep relationships with the community."

Recent years have provided substantial research displaying the effect of genetic mu-tations on the development of autism and other neurodevelopmental disorders. Based on those studies, researchers have focused attention on the commonalities be-hind those mutations and how they impact on the functioning of the brain. A study conducted by Professor Sagiv Shifman from the Life Sciences Institute at the He-brew University of Jerusalem and the Center for Autism Research has found that genes associated with autism tend to be involved in the regulation of other genes and to operate preferentially in three areas of the brain; the cortex, the striatum, and the cerebellum.

The cerebellum is responsible for motor function and recent findings have indicated that it also contributes to the development of many social and cognitive functions. Based on these findings, the research team is hopeful this can lead to a better under-standing of the relation between the cerebellum and autism and even lead to new therapies in the future.

The research study published in Nature Communications tested one of the most prominent genes associated with autism, Pogz. Professor Shifman chose this specif-ic gene based on prior findings that links it to developmental disorders and overly friendly behavior in some patients on the autism spectrum. In partnership with Professor Yosef Yarom from the Edmond & Lily Safra Center for Brain Sciences at He-brew University and other laboratories around the world, the research team investigated how a mutation in the Pogz gene impacted on brain development in mice and specifically on the functioning of the cerebellum.

The findings concluded that the mutation led to hyper-social behavior, learning disabilities while also impacting on the physical development of the mice. Upon further investigation, the research team also observed that the genetic mutation affected the proliferation of cells in the brain and inhibited the production of new neurons. The researchers believe that this may be a reason why some children with the mutation exhibit smaller than average head sizes.

While there are presently no effective medicines for the main symptoms of autism, Professor Yarom believes that this research could be instrumental in developing drugs to directly changing the neural processes in the cerebellum. Previous research conducted by Professor Yarom showed that specific chemical agents could change the active functioning of the cerebellum. Ongoing research will therefore be focused on whether similar approaches could lead the lab mice to change their behavior and reverse the effects connected with the mutation.

"Our work with this specific gene that we know is connected to autism and significantly impacts on the functioning of the brain provide us with considerable hope that we will be able to develop medicines to assist children with autism," Professor Shifman said. Professor Yarom added, "Enhanced understanding of the neurological processes behind autism opens up hope-filled possibilities for new treatments."

A shapeshifting immune system protein called XCL1 evolved from a single-shape ancestor hundreds of millions of years ago. Now, researchers at the Medical College of Wisconsin (MCW) discovered the molecular basis for how this happened. In the process they uncovered principles that scientists can use to design purpose-built nanoscale transformers for use as biosensors, components of molecular machines, and even therapeutics. The findings were published today in Science. The primary and senior authors of the manuscript, respectively, are MCW researchers Acacia Dishman, MD-PhD student, and Brian Volkman, PhD, professor of biochemistry.

Molecular switches can be used to detect cancer, construct nanoscale machines, and even build cellular computers. Many currently available molecular switches, however, rely on transcription and translation to switch "on," and cellular degradation to turn "off," meaning that they work slowly and sometimes irreversibly. Turning them on is like driving to the store, buying a lightbulb, going back home and screwing it in; and turning them off is like waiting for the bulb to burn out. Research efforts in the field have thus been devoted to developing molecular switches that work more like flicking a light switch on, and off, and on again. One way to build such switches would be to use metamorphic proteins: proteins that can adopt more than one distinct 3D shape, even under identical physiological conditions. But until now it has been difficult to define a workflow for intentional design of metamorphic proteins that could serve as nanoscale transformers optimized to perform specific biomedical functions.

Dishman and colleagues sought inspiration from nature to understand the molecular principles needed to create proteins that can assume either of two stable shapes in equilibrium. They studied the evolution of a naturally occurring metamorphic protein called XCL1, which performs two important and distinct functions in the human immune system. One conformation plays a role in directly killing invaders like viruses and bacteria, while a second attracts dendritic cells to recognize foreign antigens and kill the cells, like cancer cells, presenting them. Looking back in evolutionary time, the MCW team found that XCL1 evolved from an ancient, single-structure protein. Then about 200 million years ago XCL1 gained the power to shape-shift. By zeroing in on the precise historical timepoint when the protein started shifting between two shapes, the researchers were able to decipher the molecular code that allowed the molecular ancestors of the human XCL1 protein to become a transformer. In cracking this code, Dishman, et al. have outlined an "instruction manual" for engineering metamorphic proteins. These principles should be useful in a variety of applications, from developing biosensors to building nanoscale machines. It may now be possible, for example, to design a microscopic biobot incorporating a transformer protein acting as a drug delivery vehicle: In one conformation present in the circulation, the payload of cancer-killing drugs would remain isolated in the cargo bed. Upon approaching a tumor, signals from the cancer cells would switch the metamorphic protein into its other conformation, releasing the drug precisely at the tumor site and avoiding the damage to normal tissues that can make cancer patients sick.

"It has been an honor to work on this project," says Dishman, a fourth-year graduate student in MCW's physician scientist training program. "Our discoveries dispel some long-held misconceptions about fold switching proteins and their role in evolutionary biology. These results suggest that there may be far more shapeshifting proteins out there in the world than we ever expected. This project has been in the lab for almost a decade and it's been rewarding to solve some of the difficult questions about the evolution of XCL1. Brian gave me freedom to pursue ideas I thought were interesting and to tell the story in ways that challenge the norms in our field, and for that I am grateful. I'm thrilled to get these findings published to the broader scientific community and hope that we can go on to devise technologies that directly apply these concepts for the benefit of patients."

Adds Volkman, senior author and director of the MCW program in Chemical Biology, "Acacia's Science paper is the culmination of work that spanned many years. It does not diminish her major achievement to point out that other talented people laid the foundation, and I am grateful to all of them, especially Rob Tyler, who launched the study of XCL1 ancestor proteins. I agree with Acacia that her paper is likely to become an important landmark for the study of metamorphic proteins. Her work demonstrates that fold switching is not a biological accident but a feature that can be preserved and optimized over evolutionary time scales. I expect her paper will put to rest an alternative view that metamorphic proteins arise only as temporary, intermediate steps in the emergence of new protein structures."

The cover for issue 45 of Oncotarget features Figure 3, "Representative images of whole tumor volume segmentation of the co-registered T1 post-contrast sequence and apparent diffusion coefficient (ADC) map, yielding the corresponding ADC histogram distribution utilized for data analysis," recently published in "Diffusion-weighted MR imaging histogram analysis in HIV positive and negative patients with primary central nervous system lymphoma as a predictor of outcome and tumor proliferation" by Khan, et al.

This authors reported that the aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival and progression free survival in PCNSL.

Selection criteria yielded 90 patients, 23 patients living with HIV and 67 immunocompetent patients.

In patients with available Ki-67 expression data, nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression.

For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes.

ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.

Dr. Bilal Khan from The Baylor College of Medicine said, "Primary central nervous system lymphoma (PCNSL) is a rare subgroup of non-Hodgkin lymphoma confined to the central nervous system, with more than 90% of cases classified as Diffuse Large B-cell Lymphoma."

Diffusion weighted imaging and corresponding apparent diffusion coefficient maps can provide a representation of the cellular microenvironment with several studies demonstrating that ADC values can predict tumor cellularity across various neoplasms, including lymphomas.

In a recent similar study of whole tumor histogram analysis in PCNSL performed by the authors of this study, multiple ADC parameters were inversely correlated with Ki-67 expression and associated with poorer OS.

However, tumor segmentation was performed using only the ADC sequence with the potential inclusion of intra-tumoral necrosis, hemorrhage or regions outside of the actual solid tumor that would otherwise have been excluded with contrast co-registration, ultimately providing a suboptimal representation of true tumor parenchyma.

The primary aim of this study is to more comprehensively evaluate the relationship between ADC calculations with tumor Ki-67 expression and clinical outcomes using a larger patient sample with the inclusion of PLWH and whole tumor segmentation with T1 post contrast co-registration.

The Oncotarget author's hypothesis is that ADC values will inversely correlate with Ki-67 expression and that tumors with higher ADC values above the median will have improved OS and PFS.

The Khan Research Team concluded in their Oncotarget Research Paper that the role of MR in PCNSL historically has been the detection and qualitative evaluation of response to treatment.

DWI and derived ADC maps have been a well-established tool in neuroimaging, but the use of ADC histogram profiling has not been widely accepted in daily practice.

This data expands the role of conventional MR imaging by utilizing quantitative ADC histogram analysis to predict clinical outcomes and tumor expression of Ki-67, a biomarker for tumor proliferative activity, in immunocompetent PCNSL patients.

The role of using ADC as an imaging biomarker in PLWH may be limited.

Quantitative ADC histogram analysis should be strongly considered as part of the imaging protocol in the evaluation of immunocompetent patients with PCNSL.