Antibody Response Affects COVID-19 Outcomes in Kids and Adults

Credit: SDI Productions

Doctors can’t reliably predict whether an adult newly diagnosed with COVID-19 will recover quickly or battle life-threatening complications. The same is true for children.

Thankfully, the vast majority of kids with COVID-19 don’t get sick or show only mild flu-like symptoms. But a small percentage develop a delayed, but extremely troubling, syndrome called multisystem inflammatory syndrome in children (MIS-C). This can cause severe inflammation of the heart, lungs, kidneys, brain, and other parts of the body, coming on weeks after recovering from COVID-19. Fortunately, most kids respond to treatment and make rapid recoveries.

COVID-19’s sometimes different effects on kids likely stem not from the severity of the infection itself, but from differences in the immune response or its aftermath. Additional support for this notion comes from a new study, published in the journal Nature Medicine, that compared immune responses among children and adults with COVID-19 [1]. The study shows that the antibody responses in kids and adults with mild COVID-19 are quite similar. However, the complications seen in kids with MIS-C and adults with severe COVID-19 appear to be driven by two distinctly different types of antibodies involved in different aspects of the immune response.

The new findings come from pediatric pulmonologist Lael Yonker, Massachusetts General Hospital (MGH) Cystic Fibrosis Center, Boston, and immunologist Galit Alter, the Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge. Yonker runs a biorepository that collects samples from kids with cystic fibrosis. When the pandemic began, she started collecting plasma samples from children with mild COVID-19. Then, when Yonker and others began to see children hospitalized with MIS-C, she collected some plasma samples from them, too.

Using these plasma samples as windows into a child’s immune response, the research teams of Yonker and Alter detailed antibodies generated in 17 kids with MIS-C and 25 kids with mild COVID-19. They also profiled antibody responses of 60 adults with COVID-19, including 26 with severe disease.

Comparing antibody profiles among the four different groups, the researchers had expected children’s antibody responses to look quite different from those in adults. But they were in for a surprise. Adults and kids with mild COVID-19 showed no notable differences in their antibody profiles. The differences only came into focus when they compared antibodies in kids with MIS-C to adults with severe COVID-19.

In kids who develop MIS-C after COVID-19, they saw high levels of long-lasting immunoglobulin G (IgG) antibodies, which normally help to control an acute infection. Those high levels of IgG antibodies weren’t seen in adults or in kids with mild COVID-19. The findings suggest that in kids with MIS-C, those antibodies may activate scavenging immune cells, called macrophages, to drive inflammation and more severe illness.

In adults with severe COVID-19, the pattern differed. Instead of high levels of IgG antibodies, adults showed increased levels of another type of antibody, called immunoglobulin A (IgA). These IgA antibodies apparently were interacting with immune cells called neutrophils, which in turn led to the release of cytokines. That’s notable because the release of too many cytokines can cause what’s known as a “cytokine storm,” a severe symptom of COVID-19 that’s associated with respiratory distress syndrome, multiple organ failure, and other life-threatening complications.

To understand how a single virus can cause such different outcomes, studies like this one help to tease out their underlying immune mechanisms. While more study is needed to understand the immune response over time in both kids and adults, the hope is that these findings and others will help put us on the right path to discover better ways to help protect people of all ages from the most severe complications of COVID-19.

Reference:

[1] Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Bartsch YC, Wang C, Zohar T, Fischinger S, Atyeo C, Burke JS, Kang J, Edlow AG, Fasano A, Baden LR, Nilles EJ, Woolley AE, Karlson EW, Hopke AR, Irimia D, Fischer ES, Ryan ET, Charles RC, Julg BD, Lauffenburger DA, Yonker LM, Alter G. Nat Med. 2021 Feb 12.

Links:

COVID-19 Research (NIH)

“NIH effort seeks to understand MIS-C, range of SARS-CoV-2 effects on children,” NIH news release, March 2, 2021.

Lael Yonker (Massachusetts General Hospital, Boston)

Alter Lab (Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge)

NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute

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New study gives the most detailed look yet at the neuroscience of placebo effects

A large proportion of the benefit that a person gets from taking a real drug or receiving a treatment to alleviate pain is due to an individual’s mindset, not to the drug itself. Understanding the neural mechanisms driving this placebo effect has been a longstanding question. A meta-analysis published in Nature Communications finds that placebo treatments to reduce pain, known as placebo analgesia, reduce pain-related activity in multiple areas of the brain.
Previous studies of this kind have relied on small-scale studies, so until now, researchers did not know if the neural mechanisms underlying placebo effects observed to date would hold up across larger samples. This study represents the first large-scale mega-analysis, which looks at individual participants’ whole brain images. It enabled researchers to look at parts of the brain that they did not have sufficient resolution to look at in the past. The analysis was comprised of 20 neuroimaging studies with 600 healthy participants. The results provide new insight on the size, localization, significance and heterogeneity of placebo effects on pain-related brain activity.
The research reflects the work of an international collaborative effort by the Placebo Neuroimaging Consortium, led by Tor Wager , the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth and Ulrike Bingel, a professor at the Center for Translational Neuro- and Behavioral Sciences in the department of neurology at University Hospital Essen, for which Matthias Zunhammer and Tamás Spisák at the University Hospital Essen, served as co-authors. The meta-analysis is the second with this sample and builds on the team’s earlier research using an established pain marker developed earlier by Wager’s lab.
“Our findings demonstrate that the participants who showed the most pain reduction with the placebo also showed the largest reductions in brain areas associated with pain construction,” explains co-author Wager, who is also the principal investigator of the Cognitive and Affective Neuroscience Lab at Dartmouth. “We are still learning how the brain constructs pain experiences, but we know it’s a mix of brain areas that process input from the body and those involved in motivation and decision-making. Placebo treatment reduced activity in areas involved in early pain signaling from the body, as well as motivational circuits not tied specifically to pain.”
Across the studies in the meta-analysis, participants had indicated that they felt less pain; however, the team wanted to find out if the brain responded to the placebo in a meaningful way. Is the placebo changing the way a person constructs the experience of pain or is it changing the way a person thinks about it after the fact? Is the person really feeling less pain?
With the large sample, the researchers were able to confidently localize placebo effects to specific zones of the brain, including the thalamus and the basal ganglia. The thalamus serves as a gateway for sights and sounds and all kinds of sensory motor input. It has lots of different nuclei, which act like processing stations for different kinds of sensory input. The results showed that parts of the thalamus that are most important for pain sensation were most strongly affected by the placebo. In addition, parts of the somatosensory cortex that are integral to the early processing of painful experiences were also affected. The placebo effect also impacted the basal ganglia, which are important for motivation and connecting pain and other experiences to action. “The placebo can affect what you do with the pain and how it motivates you, which could be a larger part of what’s happening here,” says Wager. “It’s changing the circuitry that’s important for motivation.”
The findings revealed that placebo treatments reduce activity in the posterior insula, which is one of the areas that are involved in early construction of the pain experience. This is the only site in the cortex that you can stimulate and invoke the sense of pain. The major ascending pain pathway goes from parts of the thalamus to the posterior insula. The results provide evidence that the placebo affects that pathway for how pain is constructed.
Prior research has illustrated that with placebo effects, the prefrontal cortex is activated in anticipation of pain. The prefrontal cortex helps keep track of the context of the pain and maintain the belief that it exists. When the prefrontal cortex is activated, there are pathways that trigger opioid release in the midbrain that can block pain and pathways that can modify pain signaling and construction.
The team found that activation of the prefrontal cortex is heterogeneous across studies, meaning that no particular areas in this region were activated consistently or strongly across the studies. These differences across studies are similar to what is found in other areas of self-regulation, where different types of thoughts and mindsets can have different effects. For example, other work in Wager’s laboratory has found that rethinking pain by using imagery and storytelling typically activates the prefrontal cortex, but mindful acceptance does not. Placebo effects likely involve a mix of these types of processes, depending on the specifics of how it is given and people’s predispositions.
“Our results suggest that placebo effects are not restricted solely to either sensory/nociceptive or cognitive/affective processes, but likely involves a combination of mechanisms that may differ depending on the placebo paradigm and other individual factors,” explains Bingel. “The study’s findings will also contribute to future research in the development of brain biomarkers that predict an individual’s responsiveness to placebo and help distinguish placebo from analgesic drug responses, which is a key goal of the new collaborative research center, Treatment Expectation .”
Understanding the neural systems that utilize and moderate placebo responses has important implications for clinical care and drug-development. The placebo responses could be utilized in a context-, patient-, and disease-specific manner. The placebo effect could also be leveraged alongside a drug, surgery, or other treatment, as it could potentially enhance patient outcomes.

Story Source:
Materials provided by Dartmouth College. Original written by Amy D. Olson. Note: Content may be edited for style and length.

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Photographer Captures 'Last Stop' in Britain's Covid War

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storySupported byContinue reading the main storyTimes Insider‘This Is the Last Stop’: Shooting Britain’s Struggle Against CovidAfter receiving access to hospitals, nursing homes and burial sites, I saw up close the nation’s agony, and grit.Health care workers in the intensive care unit at the Homerton hospital in London turn a patient onto her back to help her breathe.Credit…Andrew Testa for The New York TimesMarch 2, 2021, 5:00 a.m. ETTimes Insider explains who we are and what we do, and delivers behind-the-scenes insights into how our journalism comes together.I had covered wars before, in the Balkans and Afghanistan. They were shooting wars where journalists — often foolishly — convinced themselves that they had a chance of identifying and sidestepping danger.But in Britain’s war against Covid-19, the days I spent as a freelance photojournalist covering the intensive care unit of the Homerton hospital in East London involved danger with every breath. The project for The New York Times documenting the nation’s fight against the coronavirus was terrifying and awe-inspiring. Terrifying because of potential exposure to an invisible killer that has claimed over 120,000 lives in Britain and more than 2.5 million globally. Awe-inspiring because I could witness the remarkable courage, professionalism and sheer grit of medical personnel whose daily routines placed them on the very cusp of life and death.Even the most advanced modern medicine offers no magic cures. For those who can’t make it out of the I.C.U., there is only death. This is the last stop. What stayed with me afterward was the fear in people’s eyes as they joined what could be the final battle. For the medical staff, the burden of responsibility is enormous.As Britain approaches a gradual loosening of its most draconian lockdown, and with millions of people securing access to vaccines, images of this terminal conflict do not fit easily into the official narrative.A vaccination center inside the Cathedral in Salisbury. Credit…Andrew Testa for The New York TimesMany Britons are probably unaware of the brutal reality of the I.C.U.: the constant bleeps of monitors everywhere; the staff hurrying to flip over, or “prone,” patients to help them breathe; the all-too-brief respites that give way to frenetic activity.Raising this awareness took months. My editors — Gaia Tripoli in London and David Furst in New York — and the researcher Amy Woodyatt and I called hospitals, mortuaries, crematories, funeral parlors and ambulance depots seeking access to chronicle this moment in the pandemic, only to be turned down. Often, we were told that photography was incompatible with the dignity of the dead.Finally, some were willing to cooperate, and after I was able to observe their toil, we began to assemble a portfolio to tell the story of Britain’s struggle. We wanted our images to reflect more than one area of London or one ethnic group. The list of subjects grew from a care home in Scarborough on the northeastern coast, to a funeral director in the English Midlands, to those dealing with Islamic and other rites in the capital.Prayers before a burial of a Muslim victim. One aim of the project was to avoid representing just one ethnic group in Britain that has been affected. Credit…Andrew Testa for The New York TimesWith this assignment came a new and unfamiliar set of ground rules and procedures designed to protect not only me but also those around me — both at work and at home..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-c7gg1r{font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:0.875rem;line-height:0.875rem;margin-bottom:15px;color:#121212 !important;}@media (min-width:740px){.css-c7gg1r{font-size:0.9375rem;line-height:0.9375rem;}}.css-1sjr751{-webkit-text-decoration:none;text-decoration:none;}.css-1sjr751 a:hover{border-bottom:1px solid #dcdcdc;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}.css-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-k9atqk{margin:0 auto;overflow:hidden;}.css-k9atqk strong{font-weight:700;}.css-k9atqk em{font-style:italic;}.css-k9atqk a{color:#326891;-webkit-text-decoration:none;text-decoration:none;border-bottom:1px solid #ccd9e3;}.css-k9atqk a:visited{color:#333;-webkit-text-decoration:none;text-decoration:none;border-bottom:1px solid #ddd;}.css-k9atqk a:hover{border-bottom:none;}Covid-19 Vaccines ›What You Need to Know About the Vaccine RolloutProviders in the U.S. are administering about 1.3 million doses of Covid-19 vaccines per day, on average. Almost 30 million people have received at least one dose, and about 7 million have been fully vaccinated. How many people have been vaccinated in your state?The U.S. is far behind several other countries in getting its population vaccinated.In the near future, travel may require digital documentation showing that passengers have been vaccinated or tested for the coronavirus.When can you get the vaccine? What are the vaccine’s side effects? Is it safe to take during pregnancy? We’ve have answers to many of your questions. In the Homerton I.C.U., they called it “donning and doffing” of personal protective equipment. I switched my day clothes for scrubs and a surgical gown; a close-sealing mask and goggles; overshoes; and a hair covering. I pared down my equipment to two cameras. And at the end of the day’s shooting, I followed a very strict protocol developed by the I.C.U. staff for removing protective gear.Once home, I laundered all my clothes, showered, cleaned equipment with anti-viral wipes and exposed it to a UVC light sanitizer. I was not eligible to be vaccinated, but I had a precautionary coronavirus test during the assignment that came up negative.The I.C.U. in the Homerton hospital. Shooting in the unit required following a strict set of safety rules. Credit…Andrew Testa for The New York TimesUltimately, I told myself, I just had to trust my equipment. But there is always gnawing doubt. The coronavirus frightens you twice over: first by its ability to infect you personally, and second by the overwhelming fear that you might inadvertently pass it on to your family.There is never any question about its power. On my second day in the Homerton I.C.U., two people died within 25 minutes of each other. Usually, the medical authorities try to provide access for family members to say goodbye. But with patients in induced comas and beyond hope, it is a cruelly one-sided exchange of farewells.And yet the counter-imagery of dedication is always there, too, just as evident in these images as the losses. As one survivor remarked, the medical teams always go the extra mile. “They are blessed,” he said.AdvertisementContinue reading the main story

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Here is What We Know About the Rollout of the Johnson & Johnson Vaccine.

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storyCovid-19: The U.S. Is Edging Toward Normal, Alarming Some OfficialsHere is what we know about the rollout of the Johnson & Johnson vaccine.March 1, 2021, 5:00 p.m. ETMarch 1, 2021, 5:00 p.m. ETJohnson & Johnson said it would start shipping millions of doses early this week after the Food and Drug Administration granted emergency use authorization for its vaccine on Saturday.CreditCredit…Pool photo by Timothy D. EasleyWhen Johnson & Johnson’s coronavirus vaccine won emergency use authorization on Saturday from the Food and Drug Administration, the move augmented the nation’s vaccination effort with a third major tool — one that differs markedly from the first two authorized vaccines, made by Pfizer-BioNTech and Moderna.Most notably, it is administered in a single dose instead of two, and can be kept unfrozen in an ordinary refrigerator for up to three months — features that promise greater flexibility as public health officials try to immunize Americans as quickly as possible.Much is still to be determined about how this new tool will be used. Here is what we know so far.When will people start getting the new vaccine?Within the next few days. Johnson & Johnson started shipping out doses on Monday, and they can be used as soon as they reach vaccination sites starting on Tuesday.Will adding the new supply speed up vaccination efforts?At first, the increase in availability will be limited. The company had about 3.9 million doses on hand to ship right away, but after that, deliveries could be patchy for a few weeks. (For comparison, the nation is using up that many doses of the Pfizer-BioNTech and Moderna vaccines in a little more than two days.)By the end of March, Johnson & Johnson says it will ship roughly 16 million more doses. Even so, the Pfizer-BioNTech and Moderna vaccines will continue to make up the majority of the nation’s supply.How is the new vaccine being allocated?The same way the two earlier vaccines are: in proportion to each state or territory’s population.Who will get the new vaccine?That’s still under discussion. The Centers for Disease Control and Prevention has said that the vaccine can be given to people 18 and over, and state officials are working out what their policies will be.Because the new vaccine is given in a single shot and doesn’t require cold storage, some experts and officials have suggested directing it toward hard-to-reach segments of the population (like rural residents or homeless people), or to people who might not keep an appointment for a second shot (like college students or those with mobility issues).But there is concern about appearing to favor or disfavor some groups, and the Biden administration has said it will insist that the new vaccine be distributed equitably.Will I be able to choose which vaccine I receive?That’s not clear. Right now, people are getting whichever vaccine the site has on hand when their turn comes, and appointment scheduling systems generally don’t tell users beforehand which it will be. Depending on how states decide to deploy the Johnson & Johnson vaccine, though, it may be possible to effectively choose what you get by choosing where you sign up to get it.Which vaccine should I prefer?Health experts say the best shot is the one you can get the soonest, whichever one it turns out to be. All three authorized vaccines are highly protective, and the differences among them pale in comparison, they say, with the risk you would run by being picky and passing up a chance to get a shot because it was not your top choice.How the Johnson & Johnson Vaccine WorksAn adenovirus helps prime the immune system to fight the coronavirus.AdvertisementContinue reading the main story

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How Johnson & Johnson's Vaccine Differs From Pfizer and Moderna's

AdvertisementContinue reading the main storyCovid-19: The U.S. Is Edging Toward Normal, Alarming Some OfficialsHere is how Johnson & Johnson’s vaccine differs from Pfizer’s and Moderna’s.Feb. 28, 2021, 2:21 p.m. ETFeb. 28, 2021, 2:21 p.m. ETThe vaccines already in wide use in the United States are given in two doses several weeks apart, while the newly authorized Johnson & Johnson vaccine is given in a single dose.Credit…Pool photo by Timothy D EasleyLeer en españolA third effective weapon was added to America’s arsenal against the coronavirus on Saturday when the Food and Drug Administration granted emergency use authorization for a vaccine developed by Johnson & Johnson.The company said it would start shipping millions of doses early this week, and would provide the United States with 100 million doses by the end of June. Together with 600 million doses of the nation’s first two authorized vaccines, made by Pfizer-BioNTech and Moderna, that are due to be delivered over the next four months, that ought to be enough to cover every American adult who wants to be vaccinated.The new vaccine differs markedly from the two already in use in the United States. Here is how they compare.One shot instead of twoThe Johnson & Johnson vaccine is administered in a single shot, while the Pfizer-BioNTech and Moderna vaccines are given in two shots several weeks apart.The way it worksThe Johnson & Johnson vaccine uses a different method to prime the body to fight off Covid-19: a viral vector called Ad26. Viral vectors are common viruses that have been genetically altered so that they do not cause illness but can still cause the immune system to build up its defenses. The Pfizer-BioNTech and Moderna vaccines use messenger RNA to do that.How well it worksThe Johnson & Johnson vaccine is rated as highly effective at preventing serious illness and death, as the Pfizer-BioNTech and Moderna vaccines are. It is also very effective at preventing milder illness, though a bit less so than those two. It appears to do well against the highly contagious B.1.351 variant, first identified in South Africa, that has given at least one other vaccine candidate trouble.Storage and handlingThe Johnson & Johnson vaccine does not have to be stored at extremely low temperatures like the Pfizer-BioNTech vaccine. It can safely be kept in an ordinary refrigerator for three months, much longer than the Moderna vaccine, which spoils after a month if not kept frozen.Side effectsThe Johnson & Johnson vaccine appears to be less prone than the Pfizer-BioNTech and Moderna vaccines to trigger the kinds of side effects that require monitoring after the injection, which may make it more suitable for use at drive-through vaccination sites. There have been reports that side effects tend to be felt more strongly after second doses, which the Johnson & Johnson vaccine does not require.AdvertisementContinue reading the main story

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Surf’s Up. The Temperature Isn’t.

Curtis Eichenberger exits the water at Lake Huron’s Georgian Bay.The World Through a LensSurf’s Up. The Temperature Isn’t.Growing numbers of surfers are taking to the Great Lakes — even when the weather is well below freezing.Curtis Eichenberger exits the water at Lake Huron’s Georgian Bay.Credit…Supported byContinue reading the main storyMarch 1, 2021It’s a cold Friday morning in late January. The snow has been falling all night. With two friends, Curtis Eichenberger and Brian McElroy, I’m heading northwest from the town of Collingwood, Ontario, to the shores of Lake Huron in Bruce County. It’s a two-hour drive, and we’re hoping the ice has taken hold of the shoreline.We park at the end of a rural road and begin the 20-minute walk to the shore. Curtis and Brian are in wetsuits and jackets, carrying their surfboards, walking down a forest path in a heavy snowstorm.I can’t help thinking that this is a quintessentially Canadian experience.Brian McElroy and Curtis Eichenberger make their way — through a snowstorm — to the shore of Lake Huron.Brian and Curtis discuss the water before hitting the waves.Our first glance at the water has Curtis and Brian excited: The waves are head high, and the sets are consistent. There are a couple of other hardy surfers out here, but it’s better than their local spot, which recently drew a crowd of some 25 people.The drive, it seems, was worth it.Curtis, suited up to surf.Curtis pours hot water in his wetsuit boots to help warm up his feet.Brian in Lake Huron.In recent years there’s been a significant increase in the popularity of lake surfing in North America. Unlike ocean surfers, who often depend partly on tides, lake surfers rely solely on strong, sustained winds. The stormy winter months often bring the biggest waves — and therefore the best surfing conditions.Curtis in Georgian Bay, at Sunset Point Beach in Collingwood, Ontario.January water temperatures on the Great Lakes are typically between 32 and 40 degrees Fahrenheit. Without a wetsuit in such temperatures, most people lose dexterity in just a few minutes. Exhaustion or loss of consciousness would occur after 15 to 30 minutes.Curtis stretches before surfing in Georgian Bay at Delphi Point Beach.Curtis, coated in ice.Still, the Great Lakes are becoming wintertime hot spots for the ocean-starved surfers who live in the area. Desperate for waves, devotees are often glued to local surf chat groups and obsessive about wind and wave forecasts.At a moment’s notice, they’re ready to clear their schedules, drive for hours, squeeze into their 6-millimeter-thick neoprene wetsuits and don (even thicker) booties and gloves, all in hopes of catching a good swell before the waves subside — or before they lose too much body heat.Surfers wait for waves in Georgian Bay.Curtis and Brian have been friends since they were kids, growing up in a small ski town north of Toronto, on Georgian Bay. They first had a taste of ocean surfing as teenagers on separate trips to New Zealand around 2003. Since then, they’ve surfed in dreamy — and warm — beach destinations all over the world: Australia, California, Costa Rica, El Salvador, Hawaii, Mexico, Nicaragua, Portugal.After driving for two hours from Toronto, Randy Luke Enns enters Georgian Bay with his surfboard at Sunset Point Beach.A surfer’s sandals are covered in snow during a lake-surfing session in Georgian Bay.“It was out of the love for ocean surfing that I ventured out into the Great Lakes,” Brian said. “Growing up landlocked, you find a way to surf throughout the year.”Matt Wilcox, a lake surfer, takes a break from surfing at Sunset Point Beach.Stephanie Hebb off the coast of Sunset Point Beach.All around the Great Lakes region — and locally in places such as Kincardine, Port Elgin and, of course, Toronto — there are surf shops that sell expensive winter surfing gear, including wetsuits and surfboards. Some of the more passionate surfers have started shaping their own surfboards in their basements or garages.Madison Tylak and Joey Braden walk into Georgian Bay at Sunset Point Beach.Jacqueline Warll and Matt Wilcox at Sunset Point Beach.There are Great Lakes surf clubs, magazines, wave forecasting seminars and competitions. And all of this is taking place hundreds of miles from the nearest ocean, and thousands of miles from the warm-ocean surf destinations that you see in movies and magazines.Georgian Bay during a snowstorm.Surfing on the Great Lakes is nothing new; people have been doing it for many decades. But what used to be a relatively niche hobby along secluded shorelines is now in full view on social media, where interest in the sport is compounding.The coronavirus pandemic has also added to its popularity. With travel restrictions in place, and with many hockey rinks, ski hills and exercise facilities closed, people have been searching for new types of exercise and entertainment — and, in particular, activities that are independent, informal and can be done closer to home and while distanced from others.Paul Reid walks into Georgian Bay.Scott Miller leaves the water after surfing in Georgian Bay at Sunset Point Beach.After two hours, Curtis and Brian emerge from the water with freezing extremities. Icicles cling to their eyebrows.Taking shelter in the trees, on the snow-covered ground, the two friends are invigorated, excited like the teenage versions of themselves who’d just learned to surf.Jordan Ward leaves the water after surfing in Lake Huron.Ryan Carter is a photographer based near Toronto. You can follow his work on Instagram.Follow New York Times Travel on Instagram, Twitter and Facebook. And sign up for our weekly Travel Dispatch newsletter to receive expert tips on traveling smarter and inspiration for your next vacation.AdvertisementContinue reading the main story

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Why I Overcame My Vaccine Hesitancy

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storySupported byContinue reading the main storyPersonal HealthWhy I Overcame My Vaccine HesitancyThe more people who become immune to the virus, the less this scourge will be able to mutate and evade the vaccines already available.Credit…Gracia LamMarch 1, 2021Had I been polled last fall, I would have registered as a Covid vaccine skeptic. I told anyone who asked that I was going to wait at least six months after a vaccine was approved, by which time I hoped we’d know more about the degree and possibly the duration of its effectiveness and its potential side effects, especially in the elderly.I was hardly alone in my concern that political influence might result in premature approval of a vaccine before its safety was well established.Well, that hesitancy quickly dissipated after listening to reports from the directors of the Food and Drug Administration and the Centers for Disease Control and Prevention and several vaccine experts I know and trust, all of whom gave an enthusiastic thumbs-up to both the Pfizer and Moderna vaccines.So in mid-January, when Gov. Andrew M. Cuomo of New York announced that residents 75 and older would qualify for the vaccine, I found a computerized link to schedule an appointment five days later.At the mass vaccination site I went to in Brooklyn, everyone I encountered was cheerful, patient and reassuring, even the young woman checking me in who couldn’t find me on her list of 3 p.m. appointments. “Don’t worry,” she said reassuringly, “you’ll get the vaccine.”At the next window, a young man from Nigeria checked my ID and Medicare card and figured out what had happened. Turned out I had inadvertently booked a 3 a.m. appointment, not realizing the site was open 24-7. Another “don’t worry,” and I moved on to a young technician from Florida who painlessly injected the Moderna vaccine into my left arm.I then sat in a holding tent for 15 minutes to be sure I would have no serious reactions. The next day I got a text: “Hi Jane, It’s time for your daily v-safe check-in” and a link to a C.D.C. site that asked: How are you feeling today? (Good, Fair, Poor); Have you had a fever or felt feverish today? (yes, no); followed by a symptom check, first at the injection site for pain, redness, swelling or itching and then generally for chills, headache, joint pains, muscle or body aches, fatigue or tiredness, nausea, vomiting, diarrhea, abdominal pain and rash or any other symptoms I wanted to report.Finally, I was asked several overall health impact questions about my ability to work and do my normal daily activities and whether I needed to consult a health care professional. I received the same text at the same time each day for more than a week, and was also given a link if I wanted to send a report to the Vaccine Adverse Event Reporting System.The second dose, administered 34 days later, went even more smoothly. By then I’d spoken to dozens of others of various ages who had gotten both shots. Only two reported bad reactions — fever, nausea, extreme fatigue — that lasted a day or two. I was prepared for the worst, but it never happened. My arm, shoulder and neck hurt the first night, but most of the pain was gone the next morning. Although my son was on call in case I couldn’t walk my dog, his help wasn’t needed. I was even able to swim that afternoon.But I assure you, even if I’d had a bad post-vaccine reaction, I would have sucked it up as a small price to pay for protection against a most devastating and too-often deadly disease like Covid-19. And I will continue to urge everyone and anyone I meet to do their damnedest to get immunized against Covid-19, especially now that potentially more potent variants are beginning to appear and spread.The Coronavirus Outbreak

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Assessing a compound's activity, not just its structure, could accelerate drug discovery

Assessing a drug compound by its activity, not simply its structure, is a new approach that could speed the search for COVID-19 therapies and reveal more potential therapies for other diseases.
This action-based focus — called biological activity-based modeling (BABM) — forms the core of a new approach developed by National Center for Advancing Translational Sciences (NCATS) researchers and others. NCATS is part of the National Institutes of Health (NIH). Researchers used BABM to look for potential anti-SARS-CoV-2 agents whose actions, not their structures, are similar to those of compounds already shown to be effective.
NCATS scientists Ruili Huang, Ph.D., and Wei Zheng, Ph.D., led the research team that created the approach. Their findings were posted online Feb. 23 by the journal Nature Biotechnology.
“With this new method, you can find completely new chemical structures based on activity profiles and then develop completely new drugs,” Huang explained. Thus, using information about a compound’s biological activity may expand the pool of promising treatments for a wide range of diseases and conditions.
When researchers seek new compounds or look for existing drugs to repurpose against new diseases, they are increasingly using screening tools to predict which drugs might be good candidates. Virtual screening, or VS, allows scientists to use advanced computer analyses to find potentially effective candidates from among millions of compounds in collections.
Traditional VS techniques look for compounds with structures similar to those known to be effective against a particular target on a pathogen or cell, for example. Those structural similarities are then assumed to deliver similar biological activities.

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With BABM, however, researchers don’t need to know a compound’s chemical structure, according to Huang. Instead, they use a profile of a compound’s activity patterns — how it behaves at multiple concentrations against a panel of targets or tests — to predict its potential effectiveness against a new target or in a new drug assay.
The now-widespread use of quantitative high-throughput screening (qHTS) allows BABM more accuracy in its predictions. qHTS assesses a compound’s effectiveness at multiple concentrations in thousands of tests over time. That practice provides far more detail about how a compound behaves than does traditional high-throughput screening, which tests only a single concentration of the compound. The information generated by qHTS creates a stronger biological activity profile — also known as a signature — for each one of millions of compounds.
To test the BABM approach, the researchers tapped the vast pool of data generated by hundreds of qHTS analyses run on NCATS’ in-house collection of more than 500,000 compounds and drugs. First, they verified BABM’s ability to use activity profiles to identify compounds already shown to be effective against the Zika and Ebola viruses. BABM also identified new compounds that showed promise against those viruses.
The scientists then turned to SARS-CoV-2, the virus that causes COVID-19. They applied BABM, a structure-based model and a combined approach to analyze the NCATS library’s compounds to find potential anti-SARS-CoV-2 agents. BABM predicted that the activity profiles of 311 compounds might indicate promise against the coronavirus.
The researchers then had an outside laboratory test those 311 compounds against the live SARS-CoV-2 virus. The result: Nearly one-third of the BABM-backed compounds (99) showed antivirus activity in the test. The BABM-driven prediction hit rate topped that of the structure-based model — and combining the activity-based and structure-based models yielded even better predictive results.
A key advantage to BABM is speed. “This method is very fast — you essentially just run a computer algorithm, and you can identify many new drug leads, even with new chemical structures,” Huang noted. In fact, screening the entire NCATS library of half a million compounds for anti-SARS-CoV-2 candidates took only a few minutes.
BABM also is a transferable tool — it’s not limited to use in the NCATS compound libraries. “Anyone can use this method by applying any biological activity profile data, including publicly available NCATS data,” Huang emphasized.
The NCATS researchers predict their activity-based model’s impact could extend far beyond the search for COVID-19 treatments and small-molecule drug discovery. Given any substance with an available activity profile, scientists can predict its activity against a new target, for a new indication, or against a new disease.
“In addition to small molecules, this approach can be applied to biologics, antibodies, and other therapies,” Huang said. “BABM is for all drug discovery projects.”

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Diagnosing Autism in the Pandemic

#masthead-section-label, #masthead-bar-one { display: none }At HomeWatch: ‘WandaVision’Travel: More SustainablyFreeze: Homemade TreatsCheck Out: Podcasters’ Favorite PodcastsAdvertisementContinue reading the main storySupported byContinue reading the main storyThe CheckupDiagnosing Autism in the PandemicAutism spectrum disorder is often suspected when young children stand out as being different from their peers. That can be much harder in this isolated time.Credit…Yifan WuMarch 1, 2021We talk often in pediatrics about the importance of early identification and early treatment of autism spectrum disorder, with its hallmark issues of social communication problems and restricted repetitive behavior patterns. “Early” means paying particularly close attention to the behavior and development of children between ages 1 and 3, and checking in with their parents about any concerns.But what does that mean for young children who have now spent half their lives — or more — in the special circumstances of the pandemic?Dr. Heidi Feldman, a professor of developmental and behavioral pediatrics at Stanford University School of Medicine, said, “We don’t know what the impact of one year of very restricted social interaction is going to be on children.” Some of the behavior patterns that children are showing now may be the result of these strange living conditions, or they may reflect stress, trauma and the social isolation that many families have experienced, she said.Dr. Feldman said that first-time parents who have been operating in the increased isolation of the pandemic may have very limited context for appreciating where their child’s behavior falls. They’re missing the input they might usually get from teachers and child care providers.Dr. Eileen Costello, a clinical professor of pediatrics at Boston University School of Medicine and chief of ambulatory pediatrics at Boston Medical Center, said, “Especially for the really little ones, the only eyes that are on them are their parents’. They’re not seeing uncles and aunts and cousins, not in preschool.”Dr. Costello and I are co-authors of the book “Quirky Kids: Understanding and Supporting Your Child With Developmental Differences.” We use the word “quirky” to encompass children whose development does not follow standard patterns, whether or not they fit the criteria for a specific diagnosis. Some of these children will accumulate several different diagnoses as they grow and change — and as different demands are made on them in terms of academic performance and social life — and others will never fit the criteria for any specific formal diagnosis.Dr. Adiaha Spinks-Franklin, a developmental behavioral pediatrician at Texas Children’s Hospital and an associate professor at Baylor College of Medicine, said that because parents right now are at home more, sometimes they are more likely to notice unusual or concerning patterns — repetitive behaviors, or communications problems like echolalia, in which a child repeats words. This can be completely normal, and is in fact part of how children learn to talk, but it can be concerning if it’s the major part of a child’s language as the child grows. By the age of 2, children should be saying lots of their own words.When parents — or teachers or doctors — do have concerns, getting a developmental assessment done has its own complexity in the pandemic.Catherine Lord, a professor of psychiatry and education at the University of California, Los Angeles, said, “I’m doing diagnoses right now in my back yard, which is insane.” But with the protective gear that would have to be worn at the hospital, she said, “we look like we’re from outer space,” and could be too intimidating to small children.Dr. Lord said. “We do remote interviews with parents, we try to see videos of the kid, then have them come — we have a big back yard.” And they continue to use the Zoom technology, even across the yard.The standardized assessment for autism spectrum disorder can’t be done masked, because it depends on interpreting the child’s expressions and observing reactions to the examiner’s facial expressions. Dr. Lord said there is a shorter version that children can do with their parents — everyone unmasked — while the clinicians watch without being in the room. This may not be as accurate — researchers are still analyzing the data — but they are hopeful that it will be helpful in many cases.“When we see kids in clinic, we have to be masked, and if they’re over 2, they have to be masked,” Dr. Feldman said. Earlier in the pandemic, a family that was convinced that their child had autism came to the clinic. “This kid had not seen anybody other than his parents and had not been anyplace other than his home — he was so terrified — the in-person visit was very, very hard.” They used a room with a one-way mirror, so the parents could be alone with the child, and could take their masks off, but “even with that, he had such a hard time settling down.”Dr. Lord was the lead author on a review paper on autism spectrum disorder published in Nature Reviews in 2020. She emphasized the importance of early diagnosis so that children can get early help with communication: “Kids who are going to become fluent speakers, their language starts to change between 2 and 3, and 3 and 4, and 4 and 5,” Dr. Lord said. “We want to be sure we optimize what happens in those years and that’s very hard to do if people are stuck at home.”She recommended that parents request the free assessments that can be done through early intervention, in many cases now being done remotely.Developmental assessments can include remote visits. “We have gotten quite good at doing telehealth evaluations,” Dr. Feldman said. “We get the kids in their own environments and their own toys, we get to see what they do at home.”“Sometimes making the diagnosis of autism over telehealth in a very young child is incredibly challenging,” Dr. Spinks-Franklin said. “Families that don’t have access to consistent reliable high-speed internet are also impacted — a video visit may not be possible or may be interrupted.”Even before the pandemic, many families faced long waits to get those developmental assessments. “Those who are vulnerable already are always going to be more severely affected — families who already had more limited access to primary care providers or are underinsured or uninsured already had a harder time,” Dr. Spinks-Franklin said.Now, she said, the pandemic is placing those families even more at risk, because of the likelihood of economic hardship from jobs loss, underemployment or lost health care benefits. The disparities are exacerbated, and the chance of getting to the right clinic and the right health care professional go down.Right now, because families are isolated or may not have good access to medical care, neurodevelopmental problems may be being missed in these critical early years, when getting diagnosed would help children get therapy. On the other hand, some children who don’t have these underlying problems and are just reacting to the strange and often anxiety-provoking circumstances of pandemic life may mistakenly be thought to be showing signs of autism.Parents and even doctors may worry about autism spectrum disorder in children who have attention deficit hyperactivity disorder or anxiety, and who are being seen in unusual situations — in a parking lot, for example. “I’ve been undoing diagnoses,” Dr. Lord said. “It’s not surprising that a kid is looking a bit less relaxed.”Dr. Spinks-Franklin said that the pressures of the pandemic may act on children as other stresses do, and show up as more extreme behavior, such as more frequent tantrums or increased irritability.“All that bounces is not A.D.H.D.; all that flaps is not autism,” Dr. Spinks-Franklin said.What Parents Can DoTo understand whether a child’s extreme behavior represents chronic stress and increased frustration related to the hardships that families are living through, or is a sign of a neurodevelopmental disorder, it’s important to figure out whether these behaviors were present before the pandemic, Dr. Spinks-Franklin said.If parents have concerns about a child’s development or behavior, a good place to start is to talk the question through with the child’s primary care provider, who can also review the record with the parents and talk about the child’s early developmental course.If parents still have concerns, it’s reasonable to request a referral for a full developmental assessment. Early intervention, a federally mandated program, offers help and therapy if a child seems to be significantly delayed in any developmental domain, but does not make diagnoses.Some developmental markers reflect a child’s early progress with speech and language, and with social interactions. The following are adapted from “Quirky Kids.”A baby babbles by 6 months, and the babble increases in complexityBy 9 months, a baby responds to his or her nameBy 15 to 18 months, a child can say some words and follow simple directionsBy 18 months, a child can put two words togetherBy 2 ½ to 3, a child can speak in simple sentences with some fluency and inflection — a question sounds like a questionBy 4 months, babies make eye contact and respond with social smilesBy 1 year, they can point to show interest, and wave goodbyeFrom about 2, they respond to other children and can interact in games with some back-and-forthAdvertisementContinue reading the main story

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Plastic Surgeon Attends Video Traffic Court From Operating Room

AdvertisementContinue reading the main storySupported byContinue reading the main storyPlastic Surgeon Attends Video Traffic Court From Operating RoomCalifornia’s Medical Board started an investigation after Dr. Scott Green reported for the hearing on Zoom while in scrubs and with a patient on the operating table.“Yes, I’m in an operating room right now,” Dr. Scott Green, a Sacramento plastic surgeon, acknowledged during a virtual traffic court hearing last week. “I’m available for trial. Go right ahead.”Feb. 28, 2021The Medical Board of California said it was investigating a plastic surgeon who attended a video traffic court hearing from an operating room while dressed in scrubs and with a patient on the surgical table.The surgeon, Dr. Scott Green, reported by videoconference for a trial in Sacramento Superior Court on Thursday.“Hello, Mr. Green? Hi, are you available for trial?” a courtroom clerk said as Dr. Green, wearing a surgical mask and cap, appeared in a virtual square with operating room lighting fixtures visible behind him. “It kind of looks like you’re in an operating room right now.”“I am, sir,” Dr. Green replied as machines beeped in the background. “Yes, I’m in an operating room right now. I’m available for trial. Go right ahead.”The clerk advised Dr. Green that the hearing, which was reported by The Sacramento Bee, would be live-streamed on YouTube.After Dr. Green was sworn in, his camera briefly swiveled and revealed a person on an operating table.Gary Link, a Sacramento Superior Court commissioner, appeared on camera.“Unless I’m mistaken, I’m seeing a defendant that’s in the middle of an operating room appearing to be actively engaged in providing services to a patient,” Mr. Link said. “Is that correct, Mr. Green? Or should I say Dr. Green?”Dr. Green confirmed that it was.Mr. Link continued, “I do not feel comfortable for the welfare of a patient if you’re in the process of operating that I would put on a trial notwithstanding the fact the officer is here today.”Dr. Green explained that there was another surgeon in the room who could perform the surgery.But Mr. Link disagreed.“I don’t think so. I don’t think that’s appropriate,” he said, adding that he would reschedule the trial for a time when Dr. Green was not operating on a patient.“We want to keep people healthy, we want to keep them alive. That’s important,” Mr. Link said. He set March 4 as a new trial date.The reason for Dr. Green’s court appearance was unclear.Dr. Green, who has offices in Sacramento and Granite Bay, Calif., did not respond to a request for comment on Sunday. Mr. Link also could not be reached.Carlos Villatoro, a spokesman for the Medical Board of California, said the board was aware of the hearing and “will be looking into it, as it does with all complaints it receives.”The board, he said, “expects physicians to follow the standard of care when treating their patients.”Mr. Villatoro declined to offer further details, citing the legal confidentiality of complaints and investigations.As court proceedings have moved online during the coronavirus pandemic, missteps have abounded.Judges have complained about lawyers attending proceedings shirtless and defendants logging on for hearings in bikinis and even naked.In February, a lawyer who could not figure out how to turn off a filter that made him look like a kitten found himself insisting to a judge that he was not, in fact, a cat.AdvertisementContinue reading the main story

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