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Physiology

A Conversation With Professor Josef Penninger on the Journey to a COVID-19 Therapeutic – Technology Networks

Professor Josef Penninger. Credit: Paul Joseph for LSI.

Angiotensin-converting enzyme 2 (ACE2) the receptor used by the SARS-CoV-2 virus as a gateway to enter and infect host cells has garnered significant attention for the wrong reasons over recent months. But could it also point towards an exit route out of this pandemic? In an interview with Technology Networks, the renowned immunologist Professor Josef Penninger nicknamed "Mr ACE2" explains why he thinks so, and discusses the latest clinical data obtained from testing the soluble ACE2 receptor, APN01.

Before the Nature paper was published, the researchers discovered that ACE2 was also expressed in the lung, a curious finding which "didn't make any sense".1 They wanted to get to the bottom of it. "All of my postdocs worked on models for intensive care units for mice so that we could study acute lung injury. At that time, between 20002003, there were maybe two or three groups on the planet which did this. The reason being it was difficult to create stable and reproducible models. My postdocs worked for many years to get the model going and then we studied ACE2 using it. We found that when we delete ACE2 in animal models the lung injury got much worse. The reninangiotensin unit is a critical component of lung injury."2

What role does ACE2 play in the body?In 2020, thanks to the contribution of Penninger and others, we now have a more thorough understanding of the role ACE2 plays in human physiology. ACE2 is an enzyme that is expressed on the membranes of cells, located in several places throughout the body, including the heart, lungs, arteries, kidneys and intestines. It is a critical component of a biochemical pathway known as the reninangiotensin system. In this pathway, ACE2 helps to modulate a protein called angiotensin II which increases blood pressure and inflammation, causing damage to blood vessels and other tissue injuries. ACE2 catalyzes the hydrolysis of angiotensin II into other molecules that counteract its harmful effects.3

However, in 2005, the World Health Organization (WHO) declared that SARS was contained. "Of course, now everyone was saying who cares. It's beautiful work but it has no relevance because there is no SARS," Penninger recalls. Fast-forward to 2020, the novel coronavirus SARS-CoV-2 has brought life to a screeching halt, and the irony of this research being declared "irrelevant" leaves a sour taste.

I asked Penninger what his initial thoughts were when the news broke of the novel coronavirus outbreak. He recalls: "It immediately clicked in my brain that ACE2 must be the target receptor for SARS-CoV-2 because of the similarities between the Spike protein of SARS and SARS-CoV-2." Sure enough, he was right. As the number of COVID-19 fatalities began to rapidly climb, scientists, industry leaders and global authorities assembled to search for an effective therapeutic against the virus.In April 2020, Apeiron announced it had received regulatory approvals in Austria, Germany and Denmark to initiate a Phase II clinical trial of APN01 in 200 severely infected COVID-19 patients. The announcement followed preclinical testing of APN01 in SARS-CoV-2 cell models and human-derived organoids. Often referred to as "mini-organs", organoids are three-dimensional cell cultures that can recapitulate, to a certain degree, the complexity of an organ.

How does APN01 work in the context of SARS-CoV-2?As APN01 imitates the ACE2 receptor, SARS-CoV-2 binds to it instead of the human form of the receptor. Consequently, the virus cannot enter and infect cells, so APN01 acts as a neutralizing agent and decoy. In parallel, APN01 reduces the inflammatory reactions in the lungs and protects against ARDS.

The preclinical data, published in Cell, reports that APN01 can "reduce viral growth in Vero E6 cells by a factor of 1,0005,000" and that "human blood vessel organoids and kidney organoids can be readily infected with SARS-CoV-2, which can be "significantly inhibited by human recombinant ACE2 at the early stage of infection."6Penninger believes that APN01 is probably "one of the most rational therapies you can think of" which goes beyond antibody therapies that work to neutralize the virus. In a press release, Professor Henning Bundgaard, principal investigator of the clinical trial and professor at the Faculty of Health and Medical Sciences at the University of Copenhagen said: We are eager to participate in this very promising and critical study. APN01 is an advanced drug candidate with a very strong dual rationale that may provide an important therapeutic contribution to fight the COVID-19 pandemic."

Infusion of APN01 was correlated with a gradual reduction in the levels of several diseas relevant mediators over the nine-day period, in addition to a rapid loss of viremia, and a delayed reduction in viral titers from tracheal samples and nasopharyngeal swabs.

Furthermore, infusion of APN01 did not adversely impact the patient's adaptive immune response, which was a huge factor of consideration, as Penninger told Technology Networks: "You could argue that if our molecule binds to the virus, it could divert the virus somehow so that immunity cannot kick in, making the disease even worse. Now we know the answer to this question and it looks very good."

Of course this data is obtained from just one patient, which must be considered. However, it's a positive start, and the Phase II APN01 clinical trial is still recruiting.

Peter Llewellyn-Davies, CEO of APEIRON Biologics, said in a press release: "We are delighted our drug candidate APN01 may have helped this patient to overcome the life-threatening disease and are confident to confirm these positive results in our ongoing and progressing pivotal clinical Phase II trial. The further scientific validation by this renowned journal encourages us in our efforts to providing an efficacious therapy against COVID-19 for the benefit of patients and society."

When asked whether he feels optimistic about the future of APN01, Penninger immediately responds: "Absolutely. The science here, that me and other companies are doing, points in the same direction. It will be interesting to see how this [APN01] plays out, in terms of viral load and the protecting of organs. As we know COVID-19 has other long-term effects in tissues around the body. ACE2 explains this distribution."

Penninger sounds confident, but not arrogant. It is evident that he truly believes in the science behind APN01; after all, he has committed many years of his research career to exploring it, discounting critics along the way. But in the context of the global pandemic, the clinical data is everything.

"What we do not know is: What dose should we use? Which timing for therapy is right? Should we start earlier? The clinical trial is testing the drug in severe COVID-19 patients. Would it work better when tested in patients for which the disease is not severe? These are the questions we have, and that's why we do careful clinical testing," he says. "I am totally confident about the science, but the clinical outcome let's see what the data tells us."Josef Penninger was speaking to Molly Campbell, Science Writer for Technology Networks.References:

1. Crackower MA, Sarao R, Oudit GY, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417(6891):822-828. doi:10.1038/nature00786.

2. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112-116. doi:10.1038/nature03712.

3. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. Treasure Island (FL): StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK470410/. Accessed September 24, 2020.

4. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-454. doi:10.1038/nature02145.

5. Khan A, Benthin C, Zeno B, et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Critical Care. 2017;21(1):234. doi:10.1186/s13054-017-1823-x

6. Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE1. Cell. 2020;181(4):905-913.e7. doi:10.1016/j.cell.2020.04.004.

7. Zoufaly A, Poglitsch M, Aberle JH, et al. Human recombinant soluble ACE2 in severe COVID-19. The Lancet Respiratory Medicine. doi:10.1016/S2213-2600(20)30418-5

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A Conversation With Professor Josef Penninger on the Journey to a COVID-19 Therapeutic - Technology Networks

Physiology

This is what happens to your body over months in isolation – CNN International

Being homebound for so long contorts the body, weakens the heart and lungs and even impairs brain function. The effects of life in isolation may stay with us beyond the pandemic's end (whenever that may be).

This is what half a year of isolation, staying home and staying sedentary can do to your body.

A week homebound, whether you're working, eating or sleeping, may feel comforting and necessary. But all the inactivity can undo hard-won progress.

That's because it can take months to build muscle and just one week to lose it. Humans, for all of our hardiness, also lose muscle more quickly the older we get, said Keith Baar, a professor of molecular exercise physiology at the University of California - Davis.

When you lose muscle, you're not necessarily losing bulk, but you are losing strength, which Baar said is one of the "strongest indicators" of how long you'll live.

"The stronger we stay, the easier it is for us to maintain our longevity."

If you're not exercising, you're not raising your heart rate. And when your heart isn't pumping as hard, it gets weaker, Baar said.

The same thing happens to your lungs when you're inactive, said Dr. Panagis Galiatsatos, a pulmonologist from Johns Hopkins Bayview Medical Center. He said many of his patients have felt their breathing function deteriorate because they're no longer conditioned to exercise.

People with poor lung health are already considered more susceptible to coronavirus because it's a respiratory illness, so they're likely staying home to reduce their risk of infection. But if they're not moving and increasing blood flow to their lungs, then their preexisting condition might harm them anyway.

Exercise is the only key to improve both heart and lung function -- "Not a single medication can do that," Galiatsatos said. If it's not safe to leave the house, Baar recommends dancing or finding household objects for home strength training -- think milk jug deadlifts.

If you're home all day, every day, you're likely feet away from your pantry. Depending on your perspective, that's either convenient or dangerous.

With such easy access, your "feeding" window, or the period of time during which you eat most of your meals, might widen from 10 or 12 hours every day to 15 hours a day-- more than half the day, which could cause your insulin levels to spike. Insulin encourages fat storage and converting other fat molecules to fat, said Giles Duffield, an associate professor of anatomy and physiology at the University of Notre Dame who studies circadian rhythms and metabolism, among other subjects.

Excessive eating is also an issue because, at the beginning of the pandemic, many people stocked up on nonperishable foods in case of supply shortages, Duffield said. Many nonperishable foods are highly processed and rich in sugars and starches.

Weight gain during periods of intense stress is normal, and 2020 has been unrelentingly stressful. Weight gain becomes dangerous, though, when it turns into obesity. Then, your body might start to resist insulin, and chronic health issues like metabolic illness or diabetes may develop, Duffield said.

We all have a seated position we subconsciously sink into -- slumped forward, shoulders hunched; spine curled, neck bent; on your chest, elbows up.

But sitting and lying down all day can seriously affect your posture and strain your back, neck, shoulders, hips and eyes, said Brandon Brown, an epidemiologist and associate professor in the Center for Healthy Communities at the University of California - Riverside.

Brown suggests getting up from your seat once an hour, walking around and stretching for a moment. You might even lie on the floor and "let your back readjust," he said.

At least half of all Americans are skimping on vitamin D, which sustains bone density and keeps fatigue at bay. You're definitely one of them if you spend most of your day at home, curtains drawn, Duffield said.

Getting enough sunlight in the morning helps synchronize your body's circadian rhythm, Duffield said. So if you're shut in all week or working in the dark, your sleep might suffer, too.

Brown said as long as you're going on walks or exercising, doing yard work or other activities that drag you outside for a bit, you won't need to worry about getting enough sunlight. If you're unable to get out of the house or the weather won't permit you to, an artificial bright light can help your body retune in the morning, Duffield said, as can avoiding blue lights at night.

A sedentary lifestyle can slow your brain, too.

Exercise produces certain chemicals in the brain that break down toxins in the blood and even prevent them from going to the brain, where they can kill brain cells, Baar said.

Not exercising means you won't as efficiently break down amino acid byproducts that wind up as neurotoxins in the brain.

The effects of isolation are insidious -- like the pandemic, the physical symptoms after months of seclusion often aren't obvious until they become harmful or extreme.

It's possible, too, to stave off those symptoms before they set in for good.

Prioritizing your mental and physical health while staying home requires some work, but it's a healthier coping mechanism for uncertainty than staying stationary until Covid-19 is no longer a threat, health experts say. And when it's safe to live fully again, you'll be prepared.

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This is what happens to your body over months in isolation - CNN International

Physiology

New research offers guidance on how often you should feed your cat – CTV News

Those piteous, all-day, I'm-so-hungry meows from your cat may not be the best guide to keeping it healthy, new research suggests.

A paper by animal health experts at the University of Guelph says cats do just fine when fed once a day -- and may even become healthier.

"I don't know why people are so set on cats having to eat multiple small meals a day," said co-author Adronie Verbrugghe.

After all, cats in the wild -- lions for example -- eat one large meal and then nothing for days.

"They're almost like dogs."

What would happen if Fluffy got her kibble in one go instead of several? Verbrugghe asked.

"There wasn't really any (research) out there that related to physiology or biochemistry."

So she and her colleagues kept careful track of eight healthy cats' activity and internal chemistry over 21 days. Four were fed once daily; the others four times. Both groups were given equal calories.

Verbrugghe found the one-meal cats had higher levels of hormones that are released when hunger has been satisfied.

"That could show they were more sated compared to the cats that were fed multiple meals," she said.

The one-meal cats also seemed to be burning more fat and showed higher levels of amino acids -- the building blocks of muscle -- than the multiple-meal cats.

The cats fed four times a day were more active, Verbrugghe said. But that doesn't mean they were burning more calories.

"When we looked at the energy expenditure, there was no difference."

Obesity is a big problem in house cats, Verbrugghe said. One meal a day could be one way of controlling that -- although she acknowledges that food plan wouldn't be acceptable to all cats.

"This is one extra tool," Verbrugghe said. "We cannot do cookie-cutter medicine. We have to create a plan for every individual animal."

But she added that demanding multiple meals is learned behaviour in some cats. It can be a way of getting attention from their owner.

"Many people are feeding multiple small meals because they want to show that they love their animals," said Verbrugghe. "I would definitely replace a meal with interacting with the animal -- giving them some cuddles, playing with them."

Cats love routine and frequent feeding may simply be part of that.

"That's how they're used to being served food," Verbrugghe said. "Other cats may have a natural grazer habit. I don't know what the reason is for that."

Sometimes, the problem behaviour is human. With many small meals, it's easy to lose track of how much food Fluffy is actually getting -- especially when children are doing the feeding.

"That could very quickly lead to weight gain."

Despite the long mutual history between humans and cats, Verbrugghe said there's still much to learn about feline physiology. People make assumptions about what their furry friends do and how they behave that aren't necessarily backed by science.

"There's still a lot of things we don't know yet. We still extrapolate a lot from other animals or humans."

This report by The Canadian Press was first published Sept. 23, 2020

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New research offers guidance on how often you should feed your cat - CTV News

Human Behavior

Can machines change human behavior? OpenWeb, using Jigsaw’s Perspective API, releases case study measuring the effects of real-time feedback and…

The study involved nearly half a million comments and 50k users across sites including AOL, Salon, Newsweek, RT, and Sky Sports; demonstrates the ability of technology to positively affect the quality of conversation.

NEW YORK, Sept. 21, 2020 /PRNewswire/ -- OpenWeb, a leading audience engagement and conversation platform released the findings of an extensive study done in collaboration with Jigsaw's Perspective API. Jigsaw is a unit within Google that forecasts and confronts emerging threats, creating future-defining research and technology to keep our world safer. Perspective API is a tool developed by Jigsaw that makes it easier to host better conversations, by using machine learning models to detect the potential toxicity of a comment.

The study measured the impact of deploying a "nudge" to potentially offensive or profane comments, encouraging commenters to reevaluate their message. The goal of the test was to measure if such a nudge could reduce toxicity within conversations. The study involved more than 400,000 comments across a select number of OpenWeb's partner publishers, including AOL, Salon, RT, and Newsweek.

In addition to testing the effect of the "nudge," OpenWeb created a variety of messages to measure how users react to different statements. The study then assessed the effect that responses to the nudge had on overall community behavior and toxicity.

Highlights from the study:

400,000 comments and 50k users were analyzed over 3 months, from May through July 2020

34% of commenters who received a nudge edited their comments

12.5% lift in civil and thoughtful comments being published overall

"The results of this case study are further evidence that technology can have an effect on human behavior," said Nadav Shoval, CEO and co-founder of OpenWeb. "There are ways machines can learn and respond to behavior and create safer environments for us all, without suppressing speech. That's what we're working to achieve."

Story continues

"We're thrilled to see more platforms using Perspective to help host better conversations online, especially platforms with such diverse and comprehensive audiences as OpenWeb. Machine learning has the potential to open up more spaces online for people to express themselves and interact with the community, but the technology is only as useful as the partners who implement it and bring it to users. This case study shows how Perspective can deliver measurable improvements in reducing toxicity. We're proud to be working with OpenWeb to bring better conversations to millions of users across the web," said Jared Cohen, Founder and CEO of Jigsaw.

"Ensuring that every member of the Salon community has an engaging experience with our features, videos, and our comments has always been a priority for us," said Mary Elizabeth Williams, Director of Community at Salon. "OpenWeb's Real-time Feedback encourages commenters to contribute their ideas and opinions in a meaningful way. News today relies on sharing, and we want that experience to be honest, insightful, and far from toxic."

OpenWeb aims to improve the quality of online discourse through extensive, layered, moderation technology and proprietary AI, and runs Perspective ML models on millions of comments to catch abuse and toxicity in real-time. This Real-Time Feedback feature gives users an opportunity to change their message if it is suspected to break the Community Guidelines, using the nudge concept, a known theory in behavioral sciences that proposes positive reinforcement and indirect suggestions as ways to influence the behavior and decision making of groups or individuals.

"We believe encouraging good behavior is equally as important as removing the bad actors to support a thriving community," said Nadav Shoval, CEO and co-founder of OpenWeb. "We want to inspire an open exchange of ideas across the web with less hostility and toxicity - and are constantly experimenting with ways to encourage and develop this."

While initially deployed as a test, due to the findings of the study, OpenWeb has begun rolling out the feature to its entire network of publishers.

To see the complete case study, and learn aboutOpenWeb's multilayered moderation, visit OpenWeb's blog.

About OpenWeb

OpenWeb (formerly Spot.IM) is on a mission to democratize and improve conversations online. The platform utilizes AI and machine learning to incentivize healthy dialogue, decrease toxicity, and create thriving, engaged communities. OpenWeb works with more than 700 top-tier publishers and hosts 100 million active users each month.

Founded in 2012, OpenWeb has 100 employees in New York City and Tel Aviv and is backed by world-class investors including Insight Partners, AltaIR Capital, ScaleUp, Norma Investments, and Index Ventures. To learn more about OpenWeb's quality conversation platform visit OpenWeb.com, or follow @OpenWebHQ onLinkedIn,Twitter, andInstagram.

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Can machines change human behavior? OpenWeb, using Jigsaw's Perspective API, releases case study measuring the effects of real-time feedback and...

Human Behavior

Research explores strategies to improve nutrition in parts of Asia and Africa – Penn State News

UNIVERSITY PARK, Pa. New studies underway in parts of Sub-Saharan Africa and South Asia are seeking answers about how best to plan and implement health services in low- and middle-income countries, as well as how to best evaluate outcomes as health services evolve. The results will inform data-driven and culturally appropriate strategies for conducting humanitarian work. In collaboration with governments, UN organizations, and community stakeholders across continents, the studies are animated by the common insight that social and behavioral variables can play a decisive role in determining the effectiveness of interventions.

Stephen Kodish, assistant professor of biobehavioral health and nutritional sciences. Kodish is advancing research on strategies to improve nutrition among vulnerable populations in South Asia and Sub-Saharan Africa.

IMAGE: Courtesy of Stephen Kodish

The research is being headed up by Stephen Kodish, assistant professor of biobehavioral health and nutritional sciences in the College of Health and Human Development, whose expertise centers on understanding the factors contributing to malnutrition among vulnerable populations. His work aims to identify the modifiable factors that influence health inequity and to work with communities to mobilize the necessary resources to reach under-served areas of the world.

Kodish is overseeing three related research projects that are intended to inform both government actions and future humanitarian initiatives.

These studies all contribute to the broader goal of satisfying nutritional requirements at key stages of development and supporting governments as they strive to achieve the UNs second sustainable development goal: end hunger, achieve food security and improved nutrition and promote sustainable agriculture.

Disease burdens fall on vulnerable populations in vastly disproportionate measure, and thats not simply an accident of fate; structural inequities create environments that are not enabling for positive health behavior change for far too many communities, Kodish said. And where enabling environments do exist, our own behavioral choices, even if motivated by good or benign intentions, have consequences. The coronavirus pandemic has underscored the importance of human behavior -- mask-wearing, staying inside, physical distancing -- all of which impact health outcomes. Were taking that behavior change focus and asking how it can be harnessed to better address malnutrition.

Kodishs research has been bolstered by the Ann Atherton Hertzler Early Career Professorship in Nutritional Sciences, a three-year appointment that began in the summer of 2019. He has used the additional financial resources to enhance his research team, which now includes co-investigators from the Penn State College of Medicine, as well as several undergraduates and two doctoral students. The early career professorship has also amplified the reach of his findings by giving him the opportunity to present research findings at an international nutrition conference held last year that was hosted by Action Against Hunger in Paris.

Kodish is slated to deliver a virtual presentation on his global health projects later this month. The event, which will cover the impetus behind his research approaches and highlight current projects in South Asia and Sub-Saharan Africa, is open to the public and will take place over Zoom at 8 p.m. Oct. 22. Details and registration information can be found by visiting the College of Health and Human Development alumni event calendar.

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Research explores strategies to improve nutrition in parts of Asia and Africa - Penn State News

Human Behavior

Studies with monkeys find early attachment brings generations of benefits – Yale News

To understand the importance of early-life attachment to mothers and how it affects the likelihood of success across generations, we can learn a lot from monkeys, say scientists.

In a long-term study of rhesus monkeys, Yale researchers have quantified the health and social benefits of secure mother-rearing and attachment. The working paper,published in the National Bureau of Economic Research, suggests that the benefits of early attachment persist for generations.

The study was led by Amanda Dettmer, associate research scientist at Yale, along with economists including Nobel laureate James Heckman from the University of Chicago, and represents a unique collaboration between primatology and economics.

Its really novel to show intergenerational effects, said Dettmer, a primatologist and behavioral neuroscientist. And its a really novel collaboration between two very different fields of study.

For the study, the scientists observed 650 mother-infant pairs. At birth, monkeys were randomly assigned to be reared by their mothers or reared in a nursery. Those monkeys who were nursery reared had human caregivers for the first 40 days and were then either assigned to a cloth surrogate with daily peer playtime, or housed together with four other monkey peers. After eight months, all monkeys were housed and treated identically. This randomization occurred in subsequent generations as well.

According to Dettmer, rhesus monkeys can reveal important insights for understanding human behavior. They share 93% of their DNA with humans, develop attachment at infancy, and have similar social structures to humans. They are very valid models for human conditions, but they develop four times faster, she said. We can get answers much faster than we can from humans.

Unlike in studies of humans, in which children cannot be randomly assigned to particular early life experiences, this experimental paradigm allowed researchers to test causality rather than simply correlation between early social experiences and later health outcomes. And because the researchers had access to data collected over four decades, they were also able to show how these early-life advantages benefited generations of descendants.

Researchers found that in cases where monkeys were reared by their mothers and descended from generations of monkeys reared by their mothers, they were most likely to have healthier outcomes later in life and to require less veterinary care. These monkeys also scored higher on dominance measures achieving a higher social ranking as evidenced through easier access to food and sweets and grooming from preferred partners.

These were the monkeys who got the banana first, Dettmer said.

Nursery-reared monkeys whose mothers were reared by their mothers did not realize the same benefits. That is, researchers found that the benefits of mother-rearing were only positive for the offspring of mothers who themselves were reared by mothers. Parenting, the authors conclude, is the primary channel of intergenerational transmission of early-life advantage.

Dettmer noted that monkeys assigned to nurseries were still given an extremely enriched environment with access to caregivers around the clock as well as daily playtime and stimulating cognitive assessments. But the absence of a mother caregiver had a lasting impact, she said.

Heckman haspreviously shownthat investments in a childs early years via quality early childhood programs yielded benefits across their lifespan.

The current paper looks at how investments in early care and secure attachments provides benefits that persist across generations. The monkeys who were nursery-reared can be equated with children who are unable to develop secure attachments, said Dettmer, such as might be experienced by those in foster care.

Dettmers lab is continuing research, not only into the health and behavioral outcomes of early attachment but also into changes that might be happening at the biological level. We want to see how early experiences influence DNA methylation and how that, too, helps to explain differences, she said.

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Studies with monkeys find early attachment brings generations of benefits - Yale News

Human Behavior

VDH: Models are tools, not predictive | Nvdaily | nvdaily.com – Northern Virginia Daily

Following months of collecting data and updating models, the Virginia Department of Health and modelers with the University of Virginia Biocomplexity Institute wrote on Friday that it's important for Virginians to understand that models help show trends but don't predict the future.

Every week, modelers write in their Data Insights Report that models are used to show what could happen with COVID-19 and are not designed to predict what will happen. As the pandemic has worn on, the data collected has become comprehensive and leads to a change in modeling from the early days of the pandemic.

Previous models showed a worst case scenario for Virginia that simply mapped a full rebound of COVID-19 spread onto the state in the long run a scenario that was not meant to be predictive, modelers wrote, but was useful to show a range of possible outcomes.

In a very real sense, the goal of models is to be wrong, modelers wrote. By alerting people to the likely consequences of the status quo, they change the future. By definition, modeling infectious disease transmission requires predicting human behavior. This is always difficult but presents particular challenges for a novel virus.

While models projecting what could happen in the future are prone to change, the constant collection of data has been useful to see how the state is adapting to the virus.

On Friday, the VDH reported the reproduction rate in Virginia remained below 1.0 and that statewide the weekly case rate is lower than the national average the United States is averaging 14,600 cases per 100,000 people and Virginia is averaging 11,000.

Modelers are projecting that Virginia will have recorded 205,931 cases by Thanksgiving.

The VDH reported 941 new cases, 37 new hospitalizations and 23 new deaths on Friday, bringing its total to 144,433 cases, 10,806 hospitalizations and 3,136 deaths since the beginning of the pandemic. Total figures include 7,150 probable cases, 85 probable hospitalizations and 206 probable deaths.

The Lord Fairfax Health District reported 12 new cases, no new hospitalizations and one new death on Friday, bringing its total to 3,072 cases, 266 hospitalizations and 111 deaths since the beginning of the pandemic. Total figures include 333 probable cases, one probable hospitalization and 10 probable deaths.

Local cases

Frederick County has had 873 cases, 66 hospitalizations and 13 deaths.

Shenandoah County has had 805 cases, 87 hospitalizations and 58 deaths.

Winchester has had 495 cases, 35 hospitalizations and four deaths.

Warren County has had 415 cases, 24 hospitalizations and seven deaths.

Page County has had 390 cases, 42 hospitalizations and 29 deaths.

Clarke County 94 cases, 12 hospitalizations and no deaths.

Regional cases

Harrisonburg has had 2,578 cases, 93 hospitalizations and 34 deaths.

Rockingham County has had 1,414 cases, 115 hospitalizations and 21 deaths.

Schools and

universities

James Madison University reported on Friday it had 89 active cases and 1,385 cases considered to be recovered since July 1. The university has had 855 students, staff and faculty self-report positive COVID-19 tests.

The University Health Center conducted 24 COVID-19 detection tests on Thursday and returned two positive test results. The health center has conducted 2,588 tests since July 1 and returned 619 positive results giving the health center a positivity rate of 24.07%.

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VDH: Models are tools, not predictive | Nvdaily | nvdaily.com - Northern Virginia Daily

Human Behavior

Shaping the post-COVID world this week: Russian vaccine diplomacy, big hits to jobs, and an unplanned climate experiment – Atlantic Council

The future is here: A guide to the post-COVID world 09/24/2020

Welcome to your guide to where the world is headed during the pandemic era and beyond. Each week, well bring you the latest and most significant expert insights and international news about how coronavirus is reshaping international affairs. To stay updated each week,sign up to the newsletter here.

Lets take a spin around the globe, in seven minutes or less.

Italians were floored by clean water in Venices canals. Indians marveled at the clean air through which they could glimpse Himalayan peaks. The pandemic abruptly arrested human activity worldwide, but some people pointed to a silver lining: The environment hadnt been treated better in decades. Sure, the signs were anecdotal, but they seemed encouraging at a time when countries were all focused on fighting COVID rather than climate change.

Now that restrictions on human movement are easing, however, global greenhouse-gas emissions have returned to within 5 percent of what they were around the same time in 2019, after initially declining by 17 percent as the COVID-19 outbreak crested in the spring, according to a new report by the World Meteorological Organization. As one climate scientist has estimated, the pandemics overall impact on climate-warming emissions could amount to only a 0.01 degree-Celsius drop in temperature.

Nevertheless, the crisis still presents a big opportunity to counteract climate change, says Joe Mascaro in a recent interview with the Atlantic Councils Foresight, Strategy, and Risks initiative, where he is a nonresident senior fellow.

Subscribe to The future is here: A guide to the post-COVID world

While the costs of the pandemic have been overwhelming, climate change will impose disruptions and calamities on a similar planetary scale. And theres now an opening to leverage one crisis to prepare for the other. We have a global situation that has created, essentially, an unplanned experiment, and one that is incredibly diverse in terms of variety of ecological systems affected, explains Mascaro, director of education and research at Planet, a provider of satellite imagery and insights. We have a chance to see how atmospheric gases, not just carbon dioxide, are altered by the massive global changes in human behavior, he notes, and I think youll see many years of research coming out of this unusual situation.

Fewer people, for example, are flying: As of mid-September, the number of scheduled flights worldwide was still down by nearly 50 percent. Fewer people are driving too: During the pandemic, the number of vehicle miles traveled fell by as much as 50 percent in the United States and 66 percent in Europe.

The bottom line: At this transitional point in the pandemic, its difficult to predict how the results of this experiment will translate into policy outcomes. And with the next UN climate-change conference, COP26, postponed until 2021 due to the coronavirus, it may take years to understand the policy consequences of this moment. But while the planet wont magically heal as a result of the sudden suspension of normal human affairs, policymakers can still draw on lessons from this peculiar period to design their responses to the climate crisis.

Insights from across the planet, in ten bullets or fewer

Insights from the Atlantic Council

Fri, Sep 18, 2020

This weeks Stories of Resilience post has been written in collaboration with the Atlantic Councils Unsung Heroes Initiative. 2020 has been a really tough year, for so many reasons. The scourge of COVID-19 has claimed hundreds of thousands of lives, and caused massive economic disruption thats brought heartbreak and hardship to millions. In the US, []

Stories of ResiliencebyAndrew R. Marshall

Fri, Sep 18, 2020

British Prime Minister Boris Johnson has found himself in an extraordinary crisis, as a second wave of COVID-19 lockdowns is interacting with what would normally be considered a totally separate matter, the future of trade deals with the European Union and the United States and Britains reputation as a nation committed to upholding international law.

New AtlanticistbyJohn M. Roberts

Wed, Sep 16, 2020

While the international community remains hyper-focused on addressing the virus and its associated economic slowdown, Afghan and Rohingya refugees continue to be forced into a life of complete uncertainty as they escape violence in their home countries. Concerted action by the international community and host countries towards mitigating the virus disproportionate effects on asylum seekers would immensely improve refugee welfare.

New AtlanticistbyRudabeh Shahid and Harris Samad

Wed, Sep 23, 2020

The pandemic has demonstrated that there are some significant fault lines in the country, US House Majority Whip James E. Clyburn told the Atlantic Council. The question now becomes whether or not were going to be able to repair those faults.

New AtlanticistbyKatherine Walla

Observations from our community

We want to learn from you.What are you noticing in your area of expertise or corner of the world about where the post-COVID international system is headed?

Email[emailprotected]with your thoughts about how the coronavirus crisis is playing out in your world, and you may be featured in an upcoming edition.

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Shaping the post-COVID world this week: Russian vaccine diplomacy, big hits to jobs, and an unplanned climate experiment - Atlantic Council

Human Behavior

The Nice Guys: A Criminally Underrated Film – The Trinity Tripod

Maciej Pradziad

A&E Editor

Shane Blacks The Nice Guys is an action-comedy film meticulously created with layers of subtle character development, endless witty quips, and scenarios that will keep you rolling in laughter throughout its almost two hour run time. Shane Black and Anthony Bagarozzi have written a screenplay that is so clever and has so much heart that it can convince anyone of having a little bit of optimism even in the face of completely hopeless odds. To top off the fantastic writing, Ryan Gosling and Russell Crowe turned in a two-man comedy performance so impressive that youll wonder why this film didnt get the rightful attention that it deserved back in 2016.

Set in 1970s Los Angeles, a down on his luck private investigator named Holland March (Ryan Gosling) is set on figuring out the mysterious death of a famous porn star. The case becomes more complicated when a girl named Amelia (Margaret Qualley) becomes a person of interest, leading to March crossing paths with his illegal private eye counterpart, Jackson Healy (Russell Crowe).

The screenplay by Black and Bagarozzi has more wit than any typical Hollywood shlock made in the past ten years. Not only is this film incredibly clever, but the cleverness actually functions within the story by either revealing character development, intricate plot points, or subverting the typical cliches of buddy cop films. The dialogue is in the perfect realm between completely unbelievable and humanely real, where the language is elevated just enough to heighten the inherently absurd peculiarities of human behavior and speech. The only potential problem with the screenplay is the structure itself and how the main villain of the film isnt revealed until halfway through the film. However, as a typical noir-ish mystery film, fun lies in figuring out the secretive person, or persons, that are creating havoc within the popular porn industry of that time, making for a very thrilling, and hilarious ride.

The performances from Ryan Gosling and Russell Crowe were genuinely masterful. No two combination of actors could have ever brought the script to life the way these two men do. The little intricacies and quirks these two performers add to their characters make them feel like theyre real people with problems bubbling underneath the surface that come out in extremely subtle ways. Furthermore, when these problems need to explode out for comic effect, they do it in spades with their perfectly timed back and forth dialogue delivery and physical comedy.

Shane Blacks The Nice Guys is a criminally underrated masterpiece from a screenwriter who has constantly renovated the action-comedy film formula.

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The Nice Guys: A Criminally Underrated Film - The Trinity Tripod

Embryology

Widow cleared to use late husband’s sperm for IVF – Press and Journal

A widow has won a landmark legal battle that will allow her to have IVF treatment using her late husbands sperm after a ruling by a panel of Scottish judges.

The woman, who has only been identified as SB, instructed lawyers to go to the Court of Session to obtain the judgment.

The court heard how SB wanted to undergo IVF treatment using sperm taken from seven vials her husband stored approximately 10 years ago but it had only been noticed when he was too ill for it to be remedied, that the correct written consent had not been given.

Her partner identified as JB had fallen ill with cancer and stored the sperm in the hope he may one day start a family.

The pair met, married and decided to have a family, but sadly he was diagnosed with cancer for a second time.

He died in 2019 after he and his wife consulted doctors about starting a family.

The court heard that when JB stored his sperm, he had given written consent to it being used for intrauterine insemination a method of conception where semen are introduced directly into the uterus.

However, he did not sign the necessary forms needed for his reproductive material to be used for IVF.

Following his marriage, JB made a will which stated that his donated sperm should be donated to his wife for as long as possible and for as long as she may wish.

Doctors, however, wanted JB to follow the process laid down by the law and sign the forms giving permission for his semen to be used in IVF treatment.

By the time an appointment was made, however, he was receiving palliative care and unable to attend.

Medics discovered the day before he died when he was unconscious that he had only completed forms which provided consent to intrauterine insemination.

Doctors told SB that her best chance for conceiving children was with IVF, prompting her legal team to go to Scotlands highest civil court to obtain an order which would allow JBs sperm to be used for IVF.

Lawyers for NHS Grampian did not oppose the move and they were not represented in the action but the Human Fertilisation and Embryology Authority was unable to conclude that JB gave effective consent, though it said if the court should find the necessary legal requirements were met, there would be no impediment for SB to begin IVF treatment.

Yesterday, judges Lady Dorrian, Lord Glennie, and Lord Woolman ruled in favour of SB.

Lady Dorrian, who gave the judgement, ruled that the mans statement in the will meant he intended his sperm to be used in IVF treatment.

The court ruled that the terms of the dead mans will amounted to effective consent to the use of his sperm for IVF treatment.

Lady Dorrian wrote: First, it is a testamentary document in which JB was not only making disposition of his estate but, by this clause, expressing his wish for the future use of his stored gametes.

Second, he and his wife had sought and been referred for treatment to enable them to have a child. Third, although it is expressed as a direction to his executors, in reality it is an expression of his wishes.

It is the sort of provision that would only sensibly be made by a man contemplating his death in the near future, and seeking to make his wishes clear.

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Widow cleared to use late husband's sperm for IVF - Press and Journal