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Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Insights From Rapid Deployment of a "Virtual Hospital" as Standard Care During the COVID-19 Pandemic

The COVID-19 pandemic has been disrupting traditional health care operations by overwhelming system resource capacity, but also has created opportunities for care innovation. Researchers from Atrium Health describe the development and rapid deployment of a virtual hospital program, Atrium Health hospital at home (AH-HaH), within a large health care system.

During their study, 1,477 patients with COVID-19 received care through a virtual observation unit (VOU) and/or a virtual acute care unit (VACU) with a median stay of 11 days. Of these, 1,293 patients received care in the VOU, and 40 patients required inpatient hospitalization. Of those 40 patients, 16 spent time in the ICU, 7 required ventilator support, and two died during hospital admission. In total, 184 patients were ever admitted to the VACU, in which 22 percent required respiratory inhaler or nebulizer treatments, 22 percent used supplemental oxygen, and 13 percent (24 patients) were admitted as an inpatient to a conventional hospital.

The researchers note that their study has limitations, such as needing patients with a working telephone and ability to comply with monitoring protocols. Overall, virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-4076.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead corresponding author, Kranthi Sitammagari, MD, can be reached directly at Kranthi.sitammagari@atriumhealth.org or 914-413-9406.

2. Sixty-Day Outcomes Among Patients Hospitalized With COVID-19

Although characteristics and in-hospital outcomes for persons with COVID-19 have been well described, less is known about the longer-term outcomes of hospitalized patients. Authors from the University of Michigan Health System and The Michigan Hospital Medicine Safety Collaborative describe 60-day postdischarge clinical, financial, and mental health outcomes of patients with COVID-19.

The authors reviewed patients hospitalized with COVID-19 at 38 participating hospitals and found nearly one in three patients died during hospitalization or within 60 days of discharge. For most patients who survived, ongoing morbidity, including the inability to return to normal activities, physical and emotional symptoms, and financial loss, was common. Adverse events after COVID-19 hospitalization are common and the authors emphasize that policies and clinical and research programs targeting these are much needed. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-5661.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Vineet Chopra MD, MSc, can be reached through Kara Gavin at kegavin@med.umich.edu.

"Age gates" that aim to keep underage users off alcohol websites are mostly ineffective, a Texas A&M University alcohol researcher found.

"Alcohol brand age gates are weak, at best, and likely an inconsequential barrier that someone with limited math abilities can easily overcome," said Adam Barry, a professor in the Department of Health and Kinesiology.

Age gates are virtual barriers intended to prevent people of ceratin age groups from accessing a website. Alcohol brand sites employ them to ensure the user attempting entry is of legal drinking age. Users are typically asked if they are 21 years of age or older, or asked to enter their birth date.

Barry's research, which was recently published in Alcohol or Alcoholism, assessed the effectiveness of the digital age gates of the top alcohol brands among American adolescents. The study found that for the vast majority of the sites, users could gain access after continuously entering dates of birth until eventually providing one indicating they were older than 21. Many sites also had no process for verifing the accuracy of the provided date of birth.

Barry is a health behavior social scientist with training and expertise in alcohol use, alcohol-induced impairment and intoxication. He said exposure to alcohol advertising can alter an adolescent's views, perceptions and expectations on alcohol consumption.

"Exposure to alcohol advertising has been linked to underage alcohol-related behaviors and intentions to consume alcohol," Barry said.

Barry's research examined alcohol webpages, but he also found that alcohol advertising on social media platforms is problematic. He said it's important to ensure that young people are not marketed to, don't interact with inappropriate content and don't fall prey to predators. However, this is often not the case.

"Unfortunately, the current strategies employed, such as asking for a birthdate, feel more like industry is concerned about their liability, as opposed to the welfare of users," Barry said.

He hopes to raise awareness of the lack of regulation in alcohol marketing. Brands themselves control the "safety measures" in place, rather than a larger entity.

"Currently, there is no formal legislation in the United States prohibiting alcohol advertisements that appeal to adolescents, the placement of alcohol advertising or how the age affirmation process and outcomes should be implemented," Barry said.

BIRMINGHAM, Ala. - University of Alabama at Birmingham researchers have discovered a previously undescribed population of neurons that help control our eyes as they view in three-dimensional space.

During normal viewing, we direct our eyes between objects in the three-dimensional space many times a minute. With each change, the left and right eyes will rotate, generally in the same direction, but mostly by different degrees of rotation. These unequal movements are known as disjunctive saccades.

Disjunctive saccades differ from two other eye movements: one, called conjugate saccades, where the eyes rotate in unison, and one called symmetrical vergence eye movements, where the eyes rotate in equal but opposite directions. The underlying mechanism for disjunctive saccades is not known.

Several models of eye movement predicted the existence of a population of neurons called saccade-vergence burst neurons, or SVBNs, that would produce a burst of activity solely during disjunctive saccades, while not firing during the other two types of eye movements.

The UAB researchers, led by Julie Quinet, Ph.D., hunted for these putative neurons in a region of the midbrain located near to the oculomotor nucleus called the central mesencephalic reticular formation, or cMRF. Recent anatomical studies had suggested that the cMRF might contain premotor neurons involved in the neural control of disjunctive saccades.

Using brain recordings from trained rhesus monkeys, Quinet and colleagues found and recorded 18 SVBNs in the cMRF. "To our knowledge," said Quinet, a researcher V in the UAB Department of Ophthalmology and Visual Sciences, "no such class of cells has been reported in prior recording studies."

This novel population of SVBNs displayed three unique characteristics that were predicted by models: 1) The neurons discharged when animals performed a disjunctive saccade; 2) The neurons remained silent during the unison eye movement called conjugate saccades and also during the eye movement when the eyes rotate in equal but opposite directions, called symmetric vergence eye movement, and; 3) The neurons burst without regard to the direction -- rightward or leftward -- of the disjunctive saccade. Furthermore, the bursts of spikes during disjunctive saccades were highly correlated with vergence velocity -- the speed at which the eyes move toward or away from each other.

Intriguingly, half of the recorded cells increased their firing rate for convergence disjunctive saccades, while half increased their firing rate for divergence disjunctive saccades.

Quinet and colleagues say that further studies of disjunctive saccades in brain areas that may supply input to SVBNs can help explain and advance solutions to treat strabismus, a condition in which eyes do not properly align with each other while looking at an object.

The results of this study and previous studies elsewhere and at UAB, Quinet says, suggest that SVBNs could play a role in all the components of the near triad responses -- lens accommodation, pupillary constriction and vergence.

Ever receive a vaccination that seemed to burn a lot while it was injected? The vaccine solution likely contained a lot of salt or sugar -- natural preservatives that help keep it stable, in addition to the cold temperature at which it was kept.

The viruses in vaccines, which train our cells to identify and vanquish viral invaders must be kept cold to keep them from bursting apart. The typical shipping temperature for vaccines ranges from 2 to 8 degrees Celsius (35 to 47 degrees Fahrenheit).

Viruses are kept cold for the same reason we refrigerate food items. "You wouldn't take a steak and leave it out on your counter for any length of time and then eat it," said Caryn Heldt, director of the Health Research Institute at Michigan Technological University and professor of chemical engineering. "A steak has the same stability issues - it has proteins, fats, and other molecules that, in order to keep them stable, we need to keep them cold."

Like proteins, viruses unfold when it's hot or there's space to move around. Heat provides energy for viruses to shake themselves apart, and not being crowded gives them the room to fall apart. Stable vaccines need cold or crowding.

But what if cold storage isn't available? What if someone accidentally leaves the package on the counter? What if the power goes out?

Heldt, together with Sarah Perry, professor of chemical engineering at the University of Massachusetts Amherst, has developed a way to mimic the body's environment in vaccines using a process called complex coacervation. Rather than relying on refrigeration, Perry and Heldt tap the other method to keep viruses stable -- crowding.

Freezer Camp

To keep the viruses in vaccines stable, everyone along the supply chain, from manufacturing facility to shipping company to doctor's office, must maintain the cold temperature. This cooperative effort is known as the cold chain. If a vaccine is kept above that temperature range for even an hour, it may become ruined and unusable.

The World Health Organization estimates that up to 50% of vaccines are wasted every year because the cold chain and ideal temperature for storage cannot be maintained.

The human body is a crowded place. Cells of varying shapes and sizes jockey for position. This includes viruses, who do their nefarious work by hostile takeover. Viruses invade our cells, commandeering them to replicate. Unchecked, virus copies explode out of the cells like darts through a balloon. Then all of those replicas go and do the same to other cells -- and before you know it, you're sick.

Heldt researches vaccine manufacturing techniques and the COVID-19 pandemic has served as a masterclass. But SARS-CoV-2 isn't the only virus in the world -- there is still need for other vaccines and storage methods that don't rely on refrigeration.

"The conditions for a vaccine that make it good to be injected into someone's body are almost the opposite of what makes a virus stable," Heldt said. "There's a really hard trade-off of keeping the virus stable to get good immune response, while having the right components in the vaccine that are safe to inject."

Virus Burritos

Heldt and Perry use polypeptides -- synthetic proteins -- that have positive or negative charges. When these charged peptides are put in solution, they stick together and form a separate liquid phase, a process called complex coacervation. The liquid wraps around virus capsids, holding the virus material together like a burrito's tortilla.

"Coacervate materials are something that we actually see all of the time in our daily lives," Perry said. "Many shampoos undergo coacervation. When you put the shampoo onto your wet hair, the water that is present dilutes the shampoo, causing it to phase separate and facilitating the removal of dirt and oil from your hair."

Complex coacervation works for nonenveloped viruses, which have no lipid, or fatty layer, around them. Nonenveloped viruses include polio, rhinovirus (which causes the common cold) and hepatitis A.

Next Steps

Heldt and Perry received a $400,000 developmental research grant in March 2020 from the National Institutes of Health (NIH) to continue their research through early 2022, which includes exploring ways to reduce salt concentrations (used in the vaccine to break apart the coacervate phase when it is injected by altering peptide sequences). Additionally, the chemical engineers are working on ways to apply complex coacervation to enveloped viruses -- like SARS-CoV-2 -- which require a balance of tightness and compartmentalization in the lipid layer in a way nonenveloped viruses do not.

"Looking forward, we want to think more about the specific materials that we use in our coacervates," Perry said. "Crowding alone isn't a universal strategy to improve virus stability. We need to understand how different polymers interact with our viruses and how we can use this to create a toolbox that can be applied to future challenges."

As the taco bar of vaccine storage expands, the research shows that naturally occurring proteins improve our vaccines and make them more widely accessible around the world, refrigerated or not.

"The great thing about these amino acids is that they are the same building blocks as in our bodies," Heldt said. "We're not adding anything to the vaccines that aren't already known to be safe."

Solving the cold storage conundrum promises to improve access to vaccinations against viruses. Bypassing the cold chain with polypeptides and innovative chemical engineering stands to improve health care and reduce medical emergencies around the world.

The effects of climate change are sometimes difficult to grasp, but now a virtual reality forest, created by geographers, can let people walk through a simulated forest of today and see what various futures may hold for the trees.

"The main problem that needs to be addressed is that climate change is abstract," said Alexander Klippel, professor of geography, Penn State. "Its meaning only unfolds in 10, 15 or 100 years. It is very hard for people to understand and plan and make decisions."

The researchers combined information on forest composition with information on forest ecology to create a forest similar to those found in Wisconsin.

"As part of an NSF-funded CNH program grant with Erica Smithwick (E. Willard and Ruby S. Miller Professor of Geography at Penn State) we are working with the Menominee Indian Tribe of Wisconsin," said Klippel, who also is director of Penn State's Center for Immersive Experience. "Inspired by the Menominee's deeper connection to the environment we believe that experiencing the future is essential for all environmental decision making."

The virtual-reality experience takes the extensive climate change models, sophisticated vegetation models and ecological models and creates a 2050 forest that people can experience by walking through it, investigating the tree types and understory, and seeing the changes.

Visualizing Forest Futures.

The first step, of course, was to create a forest of today. Using data on a typical Wisconsin forest, the researchers could have used strict or deterministic rules and placed trees in the forest. However, they chose to use a procedural method that would populate the forest using a set of ecological rules, creating a more organic, natural feel.

"Orientation and small details of the trees are also randomized in the approach so that the trees don't look exactly the same," said Jiawei Huang, graduate student in geography, Penn State.

The researchers report today (Nov. 11) in the International Journal of Geographical Information Science that, "Procedural rules allowed us to efficiently and reproducibly translate the parameters into a simulated forest." They used analytical modeling to convert the data for procedural modeling. They also worked with ecological experts to provide feedback and evaluate the results.

To capture the ecology of the forest, the researchers used LANDIS II, a well-established, powerful model.

"Our ecologist colleagues, coauthors on this paper -- Melissa S. Lucash, research assistant professor of geography, University of Oregon, and Robert M. Scheller, professor of geography, North Carolina State University -- ensured the expertise that is necessary to make the predictions accurate," said Klippel.

The researchers note that the model is powerful enough to deal with events such as windstorms, fire and flooding, and, of course, climate change.

A virtual walk through this Wisconsin forest shows tall trees and understory. Strollers, using VR headsets and controllers, can reveal the types of trees in the forest, change elevations from forest floor to birds-eye view and in-between, and more closely examine the forest composition.

The researchers chose two future scenarios, a base scenario and a hot and dry scenario. Using VR, visitors to the forest can see the changes in tree types and abundance and compare the base scenario to the hot and dry scenario.

"Our approach to create visceral experiences of forests under climate change can facilitate communication among experts, policymakers and the general public," the researchers report.

The researchers aim is to create a medium to communicate things in the future or the past that allows for a more holistic and visceral access so that non-experts can see the changes brought on by climate change.

Across the United States, weather stations made up of instruments and sensors monitor the conditions that produce our local forecasts, like air temperature, wind speed and precipitation. These systems aren’t just weather monitors, they are also potent tools for research on topics from farming to renewable energy generation.

Commercial weather stations can cost thousands of dollars, limiting both their availability and thus the amount of climate data that can be collected. But the advent of 3D printing and low-cost sensors have made it possible to build a weather station for a few hundred dollars. Could these inexpensive, homegrown versions perform as well as their pricier counterparts?

“ I didn't expect that this station would perform nearly as well as it did. Even though components started to degrade, the results show that these kinds of weather stations could be viable for shorter campaigns.” — Adam Theisen, Argonne atmospheric and Earth scientist

The answer is yes — up to a point, according to researchers, who put a 3D-printed weather station to the test in Oklahoma. Adam K. Theisen, an atmospheric and Earth scientist at the U.S. Department of Energy's (DOE) Argonne National Laboratory, led the project, which compared the printed station with a commercial-grade station for eight months to see whether it was accurate and how well it could hold up against the elements.

Three-dimensional printing uses digital models to produce physical objects on the fly. Its low cost and the ability to print parts wherever you can lug a printer could help expand the number of these stations, helping to bring data collection to remote areas and educate tomorrow's researchers.

A team at the University of Oklahoma followed the guidance and open source plans developed by the 3D-Printed Automatic Weather Station (3D-PAWS) Initiative at the University Corporation for Atmospheric Research to print over 100 weather station parts. Instead of using polylactic acid, more commonly used in 3D printing, they turned to acrylonitrile styrene acrylate, a type of plastic filament considered more durable outdoors. Coupled with low-cost sensors, the 3D-printed parts provide the basis for these new systems, which the 3D-PAWS Initiative established as promising in earlier experiments.

“In order for this to get more widespread adoption, it has to go through verification and validation studies like this,” Theisen said.

While the 3D-printed system did start showing signs of trouble about five months into the experiment — the relative humidity sensor corroded and failed, and some parts eventually degraded or broke — its measurements were on par with those from a commercial-grade station in the Oklahoma Mesonet, a network designed and implemented by scientists at the University of Oklahoma and at Oklahoma State University.

“I didn't expect that this station would perform nearly as well as it did,” said Theisen. “Even though components started to degrade, the results show that these kinds of weather stations could be viable for shorter campaigns.”

Theisen, who was based at the University of Oklahoma when the research began, continued to oversee the effort after joining Argonne.

In the experiment, the low-cost sensors accurately measured temperature, pressure, rain, UV and relative humidity. With the exception of a couple of instruments, the plastic material held up in the Oklahoma weather from mid-August 2018 to mid-April the following year, a period that saw strong rainstorms, snow and temperatures ranging from 14 to 104°F (-10 to 40°C). A 3D-printed anemometer, which measures wind speed, did not perform as well, but could be improved partly with better printing quality.

The project, which was led by undergraduate students at the University of Oklahoma, confirmed both the accuracy of a 3D-printed weather station and its value as an education tool.

“The students learned skill sets they would not have picked up in the classroom,” Theisen said. “They developed the proposal, designed the frame, and did most of the printing and wiring.”

The ability to print specialized components could make weather stations more feasible in remote areas because replacement parts could be fabricated right away when needed. And even if a cheaper sensor breaks after a few months, the math still works out for a low budget.

“If you're talking about replacing two or three of these inexpensive sensors versus maintaining and calibrating a $1,000 sensor every year, it's a strong cost-benefit to consider,” noted Theisen.

Researchers investigating the heritage of thousands of rice varieties have identified just two distinct maternal lineages, a discovery which could help address the issue of global food security.

University of Queensland scientists studied more than 3000 rice genotypes and found diversity was inherited through two maternal genomes identified in all rice varieties.

Lead researcher UQ's Professor Robert Henry said the finding was important in understanding how rice adapted to its environment.

"We think there were two separate domestications of virgin wild plants that diverged around a million years ago in the wild, and then in the last 7000 thousand years human domestication of rice has occurred," Professor Henry said.

The two domesticated varieties interbred with the local wild rices throughout Asia.

"The wild rice has pollinated the domesticated rices planted nearby and the seed of the domesticated variety has then incorporated the genetics of the local wild varieties," he said.

"The maternal lineage is preserved via the seed, and we've identified that because rice farmers have and still continue to collect the seed from the field, the local varieties become very much like the local wild rices."

Professor Henry said the finding had implications for domestication of rice and breeding for adaptation to climate change to address food security.

"It gives us clues as to how we might try to capture more of the diversity in the wild and bring it into the domesticated gene pool to improve rice crops," he said.

"It also points to the need to understand the significance of the maternal genotype in terms of performance of rice because we did not previously understand there are two very distinct maternal functional types."

Rice is the staple food of more than half of the world's population and is the third-largest worldwide agricultural crop, with more than 630 million tonnes produced annually.

"Now we've got an ongoing collaboration with mathematicians to try and find a way of analysing the rice data in more detail, we want to look at relationships between lots of different subgroups," Professor Henry said.

"This would include examining how the Basmatis and the Japonicas really relate and the various types of Indica rices."

EUGENE, Ore. - Nov. 11, 2020 - The Municipal Securities Rulemaking Board launched the Real-time Transaction Reporting System in 2005 to tighten the gap in trade reporting in municipal bond markets from a full day to fifteen minutes.

The system brought real-time price discovery to the $4 trillion over-the-counter market, transforming muni trading, investing and potentially the financing of civic projects. In a new study, a team of researchers investigated the effects of improved disclosure of trading information for muni investors and bond dealers.

In a paper, "The Difference a Day Makes: Timely Disclosure and Trading Efficiency in the Muni Market," the researchers argue that faster and more accurate disclosure benefits all major market stakeholders, finding three-fold benefits.

The paper, published online ahead of print in the Journal of Financial Economics, was written by John Chalmers and Z. Jay Wang, professors of finance in the Lundquist College of Business at the University of Oregon, and Steve Yu Liu, who earned a doctorate at the UO and is now with the Department of Business and Information Technology at the Missouri University of Science and Technology.

"First, we find a significant reduction in transaction costs that varies with investor sophistication," they wrote in the paper. "Second, we find significant increases in municipal trading volume across the liquidity spectrum. Third, we find that dealers increased market-making activities after the introduction of the RTRS."

An alternative explanation for the findings, they noted, is that they could reflect overall improvement in access to information in the over-the-counter markets due to the increased use of online resources in the period surrounding the implementation of the real-time reporting system.

To address this concern, the authors selected a subset of corporate bonds as a control group. These corporate bonds were not subject to similar changes in disclosure requirement in the sample period and should have captured the impact of common improvements to the over-the-counter markets. By comparing the changes in trading costs between the muni bonds and the control group, the authors were able to isolate the effects of RTRS, apart from other factors.

More timely disclosure in the muni markets was a particular boon to investors, with the average trading costs declining by 30 basis points or 14 percent.

Interestingly, they noted, the impact of the RTRS varies significantly across investor sophistication. While retail investors benefited mainly from a reduction in dealer's costs of intermediating trades, sophisticated traders were able to take advantage of more timely trading information and negotiate better trading terms with dealers, reflecting improved bargaining positions.

The authors also studied the impact of the RTRS on bond dealers' market making activities. They find an increase in trading volume for all bond liquidity groups sorted by pre-RTRS trading volume. Consistent with this, the researchers found, dealers committed more capital and were more actively engaged in intermediating muni bond trading in the post-RTRS period. These findings alleviate concerns that bond dealers may decrease market-making efforts due to deteriorating bargaining positions.

While switching to real-time reporting incurs additional costs, the research suggests that the sacrifices are likely to be well worth it for both investors and bond dealers. Further, by taking costs out of the system and improving investor welfare, municipalities can, in principal, benefit from cheaper access to capital markets, creating benefits for society as municipal bond offerings fund infrastructure investments that often improve quality of life, education and public safety.

More than half of people with acute COVID-19 infection continue to have persistent fatigue 10 weeks after their initial illness, according to a new study published November 9 in the open-access journal PLOS ONE by Liam Townsend of Trinity College Dublin, Ireland and colleagues.

Fatigue is one of the most common initial presenting complaints of people infected with SARS-CoV-2, the virus that causes COVID-19. The long-term consequences of COVID-19 have not been well-studied and concern has been raised that the virus has the potential to trigger a post-viral fatigue syndrome.

In the new study, researchers tracked fatigue, as well as patient characteristics including COVID-19 severity, laboratory markers, levels of inflammatory markers and pre-existing conditions, in 128 study participants who had previously been infected with SARS-CoV-2. The participants, all recruited from a post-COVID-19 outpatient clinic at St. James Hospital in Dublin, Ireland, were 54% female and averaged 49.5 years old (standard deviation ±15 years). 55.5% of the participants had been admitted to the hospital for their COVID-19 treatment while the remainder were treated as outpatients. On average, they were assessed for the study 72 days after discharge from a hospital or, if managed as an outpatient, after a timepoint 14 days following diagnosis.

Based on their score on the Chalder Fatigue Scale (CFQ-11), 52.3% (67/128) of study participants met the criteria for fatigue at the assessment point at least 6 weeks following COVID-19 infection. Only 42.2% of the patients (54/128) reported feeling back to their full health. Importantly, there was no association between COVID-19 severity, need for hospital admission, or routine laboratory markers of inflammation with the likelihood of experiencing persistent fatigue after infection. Though the study is limited in that the population cohort was predominantly white and Irish, and patients were only assessed at a single timepoint with no follow-up, the authors also found that female gender and a history of anxiety or depression was more common in the severe fatigue group (X2=9.95, p=0.002 for female; X2=5.18, p=0.02 for depression history).

The authors add: "This study highlights the burden of post-COVID fatigue. It also demonstrates that post-COVID fatigue is unrelated to severity of initial infection, so predicting its development is not easy."

More investment and important changes are needed to boost UK testing services, to tackle the COVID-19 pandemic and build a diagnostics service that will head off future UK health challenges, says a meeting report* published by the Academy of Medical Sciences today [Wednesday 11 November 2020].

The report highlights that the UK did not have an established national testing system at the start of the COVID-19 pandemic, so new systems had to be put in place rapidly. The Academy of Medical Sciences brought together 23 leading experts, to share learnings from the past ten months and discuss what changes should be made to strengthen future diagnostic testing services, at a virtual meeting on Friday 2 October 2020.

The resulting meeting report and a statement** from the Academy's Council ask for swift action to be taken to strengthen UK disease testing, including:

Enhancing collaboration across the NHS, universities and industry to make best use of their combined strengths. Representatives from these three sectors must be involved in the development of future testing strategies, with greater transparency and timely communication of decisions to all involved. This will inform academia and industry about how they can most usefully contribute.

Making sure that local laboratories can play their part in COVID-19 testing and support national approaches.

Developing and adopting more innovative ways of testing for COVID-19, for example pooling multiple samples for testing, testing for several viruses at the same time and improving packaging to speed up the analysis of samples.

Adopting a more flexible approach to regulation - also known as laboratory accreditation - so that as many laboratories as possible can contribute to national testing without unnecessary delays.

Providing longer term testing contracts to reduce any risks for companies wanting to carry out COVID-19 testing, and to enable them to contribute to current efforts.

Ensuring a sustainable workforce with a strategy to bring staff into testing laboratories, providing much needed career opportunities, including for recent graduates, in a challenging jobs market.

Professor Sir John Tooke FMedSci, Chair of the virtual roundtable, said:

"COVID-19 has shown us how important accurate, speedy diagnosis at scale is for fighting this infection. The pandemic required the expansion of UK testing services beyond anything we have ever needed in the past. At the beginning of the UK COVID-19 epidemic, important decisions around testing were necessarily made at speed. Inevitably, there were things that, with the benefit of hindsight, could have been done better and which we must address to cope with subsequent waves or future pandemics.

"We must continue to build on the collaborations between industry, academia and the NHS to take full advantage of all the talent and capabilities we possess. Despite its importance and many notable strengths the UK diagnostic sector is fragmented and underdeveloped. Now is the time to invest in our UK diagnostic services and build a system that can cope with the pandemic and whatever future health challenges we may face."

As the pandemic continues to spread over the autumn and winter months, the UK's testing capacity needs to be expanded further.

Helen Dent, Chief Operations Officer at British In Vitro Diagnostics Association (BIVDA) and attendee of the virtual roundtable, said:

"To carry out the number of tests needed, we have to bring in skills and capacity from across the UK and coordinate different sectors in a better way. This didn't happen enough in the early stages of the pandemic, for example smaller companies found it hard to get involved as the financial and contractual risks they faced were too large.

"There are a growing number of smaller biotech companies who are willing to pitch in and support the UK testing system. Let's find a way to get as many labs as possible involved so we can get the country through this pandemic while also putting much needed funds into our own economy."

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences, said:

"One of the most wicked and unusual features of COVID-19 is that you can have it, not know you have it and yet still infect others. The fact that COVID-19 symptoms have commonalities with many other diseases such as the common cold means that testing is one of the most important tools to fight COVID-19, alongside handwashing and physical distancing, so that people can isolate and reduce the spread of infection. So it is vital that we do all we can to improve and strengthen our testing services to head off the pandemic.

"When testing services were rapidly expanded at the start of the UK epidemic, there was not enough energy put into building up partnerships between university research laboratories, the NHS and industry. This held up progress earlier in the year, but there are a few fantastic examples where collaboration increased testing capacity that we can learn from. For example, in Norfolk a local collaboration between the Norwich Research Park Partners has seen The Earlham Institute and the University of East Anglia (UEA) support the Norfolk and Norwich University Hospital to scale up COVID-19 testing capacity, leading to a seven-fold increase in test processing.

"The pandemic has now catalysed a level of cross sector collaboration we have never seen before. The crucial thing is to prioritise retaining and strengthening these bonds. If we manage to do this, we can build a diagnostic system that will be able to cope with further waves of COVID-19 infections, possible future epidemics and help meet the demands for tests for other diseases such as cancer and heart disease."

Professor Sir John Tooke added:

"Doing the best job of testing demands the inclusion of expert voices from NHS, academia and industry in developing plans, and ensuring that local efforts complement national strategy.

"To meet increasing testing requirements, we need faster accreditation for diagnostic laboratories, by cutting red tape to get as many labs as possible involved in the national testing effort. We have seen how new treatments can be approved more quickly during the pandemic without losing important safety and efficacy checks - the same needs to happen for accrediting laboratories doing testing.

"In the early stages of the pandemic many volunteer technicians and students were brought into testing laboratories. Many of these skilled volunteers have returned to their day jobs, so we now need to reinvest and train more laboratory staff to replenish this pool of workers. This will provide much needed employment opportunities, including for graduates, in a challenging jobs market.

"Finally we need to find new and innovative ways of testing for COVID-19 - and to make sure that the incredible discoveries being made in UK and international research institutes make it through to testing facilities. Innovative testing systems combined with hand washing, physical distancing and isolation will help us get a hold on the spread of infection and get us back to what we remember as 'normal' life - visiting grandparents, going to the theatre and football matches and travelling abroad safely."

HANOVER, N.H. - Tuesday, November 10, 2020 - A "molecular volume knob" regulating electrical signals in the brain helps with learning and memory, according to a Dartmouth study.

The molecular system controls the width of electrical signals that flow across synapses between neurons.

The finding of the control mechanism, and the identification of the molecule that regulates it, could help researchers in their search for ways to manage neurological disorders, including Alzheimer's disease, Parkinson's disease and epilepsy.

The research, published in Proceedings of the National Academy of Sciences, describes the first study of how the shapes of electrical signals contribute to the functioning of synapses.

"The synapses in our brain are highly dynamic and speak in a range of whispers and shouts," said Michael Hoppa, an assistant professor of biological sciences at Dartmouth and the research lead. "This finding puts us on a straighter path toward being able to cure stubborn neurological disorders."

Synapses are tiny contact points that allow neurons in the brain to communicate at different frequencies. The brain converts electrical inputs from the neurons into chemical neurotransmitters that travel across these synaptic spaces.

The amount of neurotransmitter released changes the numbers and patterns of neurons activated within circuits of the brain. That reshaping of synaptic connection strength is how learning happens and how memories are formed.

Two functions support these processes of memory and learning. One, known as facilitation, is a series of increasingly rapid spikes that amplifies the signals that change a synapse's shape. The other, depression, reduces the signals. Together, these two forms of plasticity keep the brain in balance and prevent neurological disorders such as seizures.

"As we age, its critical to be able to maintain strengthened synapses. We need a good balance of plasticity in our brain, but also stabilization of synaptic connections," said Hoppa.

The research focused on the hippocampus, the center of the brain that is responsible for learning and memory.

In the study, the research team found that the electric spikes are delivered as analog signals whose shape impacts the magnitude of chemical neurotransmitter released across the synapses. This mechanism functions similar to a light dimmer with variable settings. Previous research considered the spikes to be delivered as a digital signal, more akin to a light switch that operates only in the "on" and "off" positions.

"The finding that these electric spikes are analog unlocks our understanding of how the brain works to form memory and learning," said In Ha Cho, a postdoctoral fellow at Dartmouth and first author of the study. "The use of analog signals provides an easier pathway to modulate the strength of brain circuits."

Nobel laureate Eric Kandel conducted work on the connection between learning and the change in shapes of electrical signals in marine sea slugs in 1970. The process was not thought to occur in the more complex synapses found in the mammalian brain at the time.

Beyond discovering that the electrical signals which flow across synapses in the brain's hippocampus are analog, the Dartmouth research also identified the molecule that regulates the electrical signals.

The molecule--known as Kvβ1--was previously shown to regulate potassium currents, but was not known to have any role in the synapse controlling the shape of electrical signals. These findings help explain why loss of Kvβ1 molecules had previously been shown to negatively impact learning, memory and sleep in mice and fruit flies.

The research also reveals the processes that allow the brain to have such high computational power at such low energy. A single, analog electrical impulse can carry multi-bit information, allowing greater control with low frequency signals.

"This helps our understanding of how our brain is able to work at supercomputer levels with much lower rates of electrical impulses and the energy equivalent of a refrigerator light bulb. The more we learn about these levels of control, it helps us learn how our brains are so efficient," said Hoppa.

For decades, researchers have searched for molecular regulators of synaptic plasticity by focusing on the molecular machinery of chemical release. Until now, measurements of the electrical pulses had been difficult to observe due to the small size of the nerve terminals.

The new research finding was enabled by technology developed at Dartmouth to measure voltage and neurotransmitter release with techniques using light to measure electrical signals in synaptic connections between neurons in the brain.

In future work, the team will seek to determine how the discovery relates to changes in brain metabolism that occur during aging and cause common neurological disorders.

According to the research team, the molecular system exists in an area of the brain that is easily targeted by pharmaceuticals and could lend itself to the development of drug therapies.

Hearing loss is the second most common disability in the United States and comes with it a higher risk for being diagnosed with significant health conditions, such as hypertension, diabetes, dementia and depression, as well as higher health care cost and use. The Early Auditory Referral-Primary Care (EAR-PC) study was designed to address the lack of data about hearing loss screening. Implemented in real-world, community-based clinics, it evaluated the effect of a tailored electronic clinical alert appearing at all visits of patients 55 and older, to encourage clinicians to ask, "Do you have difficulty with your hearing?" The study's lead author is Philip Zazove, M.D., who is hearing impaired. He and his team of researchers evaluated a screening paradigm for identifying patients 55 years and older at risk of hearing loss from 10 family medicine clinics in two health systems for formal hearing evaluation and treatment. An electronic prompt alerted clinicians to screen for hearing loss during visits. About 25 percent of the patients had signs of hearing loss with the primary care screener (Hearing Handicap Inventory for the Elderly). Referral rates to audiology specialists increased from baseline rates of 3.2 percent to 14.4 percent at one health system and 0.7 percent to 4.7 percent at the other. Considering the high prevalence of hearing loss and the impact on quality of life, increasing referral rates for audiology testing may improve health outcomes.

Effective Hearing Loss Screening in Primary Care: The Early Auditory Referral-Primary Care Study
Philip Zazove, MD, MM, et al
University of Michigan, School of Medicine, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/520

Primary Care Teams Test New Tool to Prescribe Referrals for Community Health and Social Services

Family physicians provide the majority of health care for underserved rural and urban populations in the U.S. and treat a more diverse population of patients than any other medical specialty. They have an important role to play in helping to mitigate health inequities by connecting patients to community-based wellness and self-care resources such as food and nutrition supports, weight management and smoking cessation to support them in preventing and managing cardiovascular disease.

CommunityRx-H3 is a practice-level, customizable community resource referral system that uses evidence-based algorithms to auto-generate a list of community resources to address such needs. This study evaluated the implementation of CommunityRx-H3 through the perspective of primary care practice facilitators.

This study found that practice facilitators can play a key role in implementing quality improvement initiatives like CommunityRx-H3. However, it also underscores the importance of support from an engaged practice leadership to address such barriers as: limited time, lack of staff, staff apathy, material resources (e.g., printers and paper) and lack of integration between a community resource referral system and the practice's EMR system.

Implementation of Community-Based Resource Referrals for Cardiovascular Disease Self-Management
Emily Abramsohn, MPH, et al
The University of Chicago, Chicago, Illinois
https://www.annfammed.org/content/18/6/511

Under-Insured Transgender Americans Turn to Riskier, Non-Licensed Sources for Gender-Affirming Hormones

Transgender people who lack access to insurance coverage for gender-affirming hormone therapy are more likely to use hormones from sources other than a licensed prescriber, compared to those with insurance coverage. Analysis of the most recent United States Transgender Survey shows that about 9 percent of transgender adults - which comes to about 170,000 transgender adults in the U.S. today - access hormones from non-licensed sources like friends or online. The study found an association between the use of non-prescribed hormones and lack of health insurance or denial of insurance coverage for gender-affirming medical care. Survey respondents also identified insurance coverage as a prevailing barrier; it was ranked as a top issue affecting transgender people in the United States, ranked second only to direct violence.

The authors note that hormones accessed from an unlicensed source may pose health and safety risks, as medications may be unmonitored for content, quality, formulation and dosing. Additionally, use of non-prescription hormones likely entails decreased monitoring of hormone levels and less opportunity for mitigating risks or other forms of harm reduction and preventive care.

Insurance Coverage and Use of Hormones Among Transgender Respondents to a National Survey
Daphna Stroumsa, MD, MPH, et al
University of Michigan, Ann Arbor, Michigan
https://www.annfammed.org/content/18/6/528

New Analysis Finds Lung Cancer Screening Reduces Rates of Lung Cancer-Specific Death

Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening. Researchers at the University of Georgia analyzed the health outcomes of 90,275 patients, comparing those who were screened versus those who received usual medical care or chest x-rays. Their analysis found a clinically and statistically significant 0.4 percent reduction in lung cancer-caused death long term, which translates into one preventable death per 250 at-risk adults screened. The authors recognize the important potential harm of overdiagnosis in cancer screening programs, and there was some evidence of overdiagnosis due to increased incidence in the screened group. However, based on the reduction in all-cause mortality being in the same direction and magnitude as lung cancer mortality, the authors interpret that the associated harms "do not appear to increase other causes of mortality," and the results of the study align with the U.S. Preventive Services Task Force recommendations for CT-based lung cancer screenings for adults age 55 to 80 who have a history of regular smoking.

Cancer-Specific Mortality, All-Cause Mortality, and Overdiagnosis in Lung Cancer Screening Trials: A Meta-Analysis
Mark H. Ebell MD, MS, et al
University of Georgia, College of Public Health, Athens, Georgia
https://www.annfammed.org/content/18/6/545