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SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesMultinational companies have halted some operations as China widens its Covid lockdowns – among its biggest since the start of the pandemic.Tens of millions of people across the country face restrictions, including the entire Jilin province and technology hub Shenzhen, as authorities report record numbers of cases.Toyota, Volkswagen and Apple supplier Foxconn are among the firms affected.The lockdowns have raised concerns that crucial supply chains may be disrupted. China on Tuesday reported a record high of more than 5,000 cases, most of it in Jilin.All 24 million residents of the north-eastern province were placed under quarantine orders on Monday. It is the first time China has restricted an entire province since the Wuhan and Hebei lockdown at the beginning of the pandemic. Jilin residents have been banned from moving around, and anyone wanting to leave the province must apply for police permission. It came a day after a five-day lockdown was placed on the 12.5 million residents of the southern city of Shenzhen, with all buses and subway services suspended. On Tuesday authorities in Langfang city which borders the capital Beijing, as well as Dongguan in the southern province of Guangdong, also imposed immediate lockdowns.The messy cost of China’s harsh lockdown playbookWhy China is still trying to achieve zero CovidBusinesses in many of the affected regions have been told to close or have their employees work from home, unless they supplied essential services like food, utilities or other necessities. Foxconn, which manufactures iPhones for Apple, stopped its operations in Shenzhen on Monday, saying the date of resumption would “be advised by the local government”. But it has several production sites in China and told the BBC it had “adjusted the production line to minimise the potential impact”. Its plant in Zhengzhou – the world’s largest iPhone factory – remains open, as the city was not hit by the restrictions. Toyota, which shut its factory in Changchun city in Jilin province, did not give a timeline for when business would resume. The Japanese carmaker told the BBC that the move was made to consider the “impact of supplier operation”, and the “safety and security of employees and related parties”. German carmaker Volkswagen also shuttered operations in Changchun, saying production of Volkswagen and Audi cars and their components were “affected”, but that it hoped to reopen its factory on Thursday. On Tuesday the Shanghai Composite lost 5% and the Hang Seng index, where several Chinese technology giants are listed, fell over 6%.Analysts believe that firms would be able to manage the disruptions. “Such lockdowns have happened before, and (cities) have re-opened within a short period of time once the number of Covid cases were within control,” Yeang Cheng Ling, senior investment strategist at Singapore’s DBS Bank, told the BBC.UBS analyst Grace Chen said Shenzhen was not a “major” production site for suppliers, but it would be worrying if the lockdowns extended to Shanghai and surrounding areas as the region is a key manufacturing hub for notebooks, servers, and smart devices.It feels like China has gone backwards. Two years backwards. To the early days of the outbreak that first emerged here. Drastic measures are being imposed – again – on a large scale, to try to contain the virus. An entire province has been sealed off. The lockdown of Jilin is similar in so many ways to Hubei in early 2020; the area of China where it all began. Shenzhen, the globally important tech hub (where your iPad was most likely made) is also a city in lockdown. Shanghai – where I am writing this – home to 24 million people, is a nervous place. All schools are closed, children are learning online, increasingly people are working from home. Some compounds where people live are enforcing strict rules on who can come in. Deliveries are being sprayed with disinfectant again at the gates. It’s all part of the on-going effort to maintain/retain/regain China’s “dynamic zero-Covid” strategy. A goal that has been boosted by the mass roll-out of China’s homemade vaccines. A goal that has been helped hugely by effectively shutting China’s borders. But now a goal that is being significantly undermined by the Omicron variant.China has seen relatively fewer cases of Covid due to its strict zero-Covid policy, where it resorts to rapid lockdowns, mass testing and travel restrictions whenever clusters have emerged. However the rapid transmissibility of the Omicron variant has made sticking to that approach increasingly challenging. Since the start of the year, China has reported more domestically transmitted cases than in the entire 2021. Top Chinese infectious disease expert Zhang Wenhong has called the recent outbreaks “the most difficult period in the last two years of battling Covid” and that they were still in “the early stage of an exponential rise”, in an online post widely circulated on social media.But he added that while it was necessary for China to maintain its zero Covid strategy to control the outbreaks for now, “this does not necessarily mean we will continue implementing the strategy of lockdowns and mass testing forever”.You may also be interested in: This video can not be playedTo play this video you need to enable JavaScript in your browser.More on this storyBeijing urges end to foreign deliveries over CovidThe messy cost of China’s harsh lockdown playbookWhy China is still trying to achieve zero CovidThe road back to Wuhan

Researchers in Atlanta have helped the federal government evaluate dozens of Covid tests and pioneer a new model for developing novel diagnostics.ATLANTA — When the pandemic hit two years ago, the United States faced an acute shortage of reliable Covid-19 tests. It was the nation’s first major pandemic failure, blinding health experts and the public to the spread of the coronavirus and allowing the pathogen to spread across the country unchecked. And for much of 2020, getting tested required waiting hours just to be swabbed and a week or longer for results.Now, hundreds of millions of rapid, at-home tests are pouring into the American market every month. The federal government is mailing out free tests, Americans are trading swabbing tips on social media and children are spitting into collection tubes at school.The flashiest developments in medicine typically involve treatments and cures, but the pandemic has been a case study in the importance of diagnostics. That is our first line of defense against disease: “Knowing early, knowing fast and doing something about it,” said Robert Nobles, vice president for research administration at Emory University.Over the last two years, a group of researchers at Emory and other Atlanta institutions has played a key, but largely hidden, role in getting Covid tests into the hands of Americans, working with the National Institutes of Health and the Food and Drug Administration.“We kind of functioned as their eyes and hands to answer the question, Do these tests work?” said Dr. Wilbur Lam, a pediatric hematologist and bioengineer at Emory and the Georgia Institute of Technology. “Essentially, we’re testing the tests.”Dr. Lam and more than 200 colleagues — physicians, engineers, biochemists and more — have worked late nights and early mornings to accelerate the development of new tests and ensure that existing products can detect an alphabet of new variants, including Omicron.The Atlanta team “has been absolutely heroic,” said Bruce Tromberg, director of the N.I.H.’s National Institute of Biomedical Imaging and Bioengineering.Developing new tests, especially those designed to be used by the average consumer, is tricky, and the work that the Atlanta team has done illustrates how much meticulous research is required to get it right. The team’s work also provides a model that could help us be better prepared for future pandemics and usher in a new era of at-home diagnosis for all kinds of diseases.“What we found through the pandemic, and have created out of the urgency, is a new mechanism for moving many of these technologies from what we like to describe as blackboard to bench top to bedside much more quickly,” Dr. Tromberg said.Sarah Hernandez begins preparing samples for P.C.R. testing and sequencing in a biosafety cabinet in the Waggoner Laboratory at Emory University.Johnathon Kelso for The New York TimesThe first testsOn a rainy February morning, Simeon Shelton, 15, sat in his mother’s car in a church parking lot in Atlanta, feeling congested and achy. He had arrived at the drive-through testing site for a standard P.C.R. test but grew intrigued when a researcher approached with a question: Would he like to help scientists evaluate a new Covid test?Simeon was eager to help. So he sat in the passenger seat, with a nasal swab, a plastic test cartridge and a fluid-filled test tube all arranged on a tray on his lap. He read the instructions and carefully swirled the swab in each nostril. “I was just kind of nervous that I would mess it up,” he said moments later.But the instructions had been easy to follow, he told the researcher standing outside his window, and in 15 minutes his results were in: negative.The study, part of a coordinated federal effort to get more Covid tests on pharmacy shelves, would help the F.D.A. decide whether to authorize the product, which was already available abroad.“The goal is to bring those tests into the American market,” Dr. Lam said. “But first, there’s a pit stop in Atlanta.”Dr. Lam is slight and sprightly, with black-frame glasses and a youthful energy that fills every room he enters. When Dr. Lam was in graduate school, his son’s terrible ear infections spurred him and a colleague to invent a smartphone attachment that allowed parents to snap photos of their children’s eardrums — and doctors to diagnose infections remotely.In 2018, Dr. Lam established a diagnostic research center with two other colleagues: Oliver Brand, an engineer at Georgia Tech, and Dr. Greg Martin, a pulmonologist and critical care doctor at Emory. The mission of the Atlanta Center for Microsystems Engineered Point-of-Care Technologies was to help companies, scientists and inventors develop high-tech diagnostic devices that could be used outside the laboratory.A BinaxNOW Covid test at a clinical pathology lab at Emory University.Johnathon Kelso for The New York TimesFrom left: Oliver Brand, Dr. Wilbur Lam and Dr. Greg Martin, who together established the Atlanta Center for Microsystems Engineered Point-of-Care Technologies.Johnathon Kelso for The New York TimesThe N.I.H.-funded center — a collaboration between Emory, Georgia Tech and Children’s Healthcare of Atlanta — had been open barely a year when Covid arrived. “We were, I think, uniquely suited then to try and help,” Dr. Lam said.The N.I.H., which worked closely with the Atlanta researchers, thought so, too. So the agency enlisted the Atlanta center to play a key role in a new N.I.H. initiative, created in the spring of 2020: the Rapid Acceleration of Diagnostics program, or RADx, which was designed to help Covid test developers quickly refine, commercialize and scale up their products.The applications poured in by the hundreds. “You’ve got all these people saying, ‘We have this great idea, give us money,’” said Dr. Tromberg, who leads the test-development arm of RADx. “How do you know if it’s really working?”The Atlanta team was tasked with answering this question.On a recent afternoon, the Emory virologists Leda Bassit and Anuradha Rao demonstrated the process in a quiet second-floor laboratory, where an assortment of at-home test strips and cartridges was arrayed on a lab bench. In the early days of the pandemic, the women had forged a fast friendship over many days spent in the Biosafety Level 3 laboratory, clad in personal protective equipment, growing live coronavirus and using it to test the tests. “We did a lot of work in the BSL-3,” Dr. Bassit said. “Spent hours and hours.”But over the last two years, the team amassed tens of thousands of patient samples in the basement “freezer farm,” a small, windowless room that holds rows of frost-encrusted appliances, maintained at minus 80 degrees Celsius and named for characters from the Marvel universe or the television show “Schitt’s Creek.”Now, the scientists often make highly concentrated viral slurries from patient samples pulled, in a blast of frigid air, from “Wolverine” or “David Rose.”To assess the sensitivity of a single product, they test it with viral samples at a range of concentrations, using the same components that consumers would receive and following the same instructions.Holding a nasal swab in one gloved hand and a pipette in the other, Dr. Bassit drew a bit of concentrated viral solution out of a tiny blue test tube and gently expelled it onto the swab. She twirled the swab in a tube containing liquid buffer, then added a thin test strip to the tube, nestling it beside the swab. Within minutes, two pink lines blazed across the strip: It was positive.The scientists repeated this process over and over again, sometimes 75 or 80 times per product, photographing and logging each result. The most sensitive tests turned positive even when the virus was very dilute; less sensitive ones only detected the virus at the highest concentrations.Beyond the lab benchA researcher with the Atlanta Center for Microsystems Engineered Point-of-Care Technologies registering study volunteers at a drive-through testing site in the city.Johnathon Kelso for The New York TimesProducts that performed well in the lab were evaluated at local Covid testing sites — like that rainy church parking lot — where people could volunteer to provide extra samples. “And we would test whatever test du jour,” Dr. Lam said.Not all tests held up; some saliva tests, for instance, missed a lot of real-world infections. “They then pivoted to a nasal sample type, which worked beautifully,” said Julie Sullivan, chief operating officer for the Atlanta RADx efforts.Researchers also assessed the user-friendliness of each product. “You want to make sure that nothing requires too much force, make sure that it’s easy to grasp, grip,” said Sarah Farmer, managing director of Georgia Tech’s HomeLab. “Let’s streamline it where possible, cut down steps where possible.”Maxim Biomedical, a Maryland-based company that makes a rapid antigen test, added a test-tube stand after researchers noticed that users could not set the liquid-filled, round-bottomed tube down on a table. “Their data played a big part in our development and optimization of the test,” said Jonathan Maa, the company’s chief operating officer. (The company hopes to use what it learned to design other consumer-friendly tests, he said.)To identify tests that could be scaled up quickly, the researchers also rated the “technology readiness” of each test. Some otherwise promising breath-based devices performed poorly on this measure. “When we looked at them, they really were not mature enough to succeed,” Dr. Martin said.They also took each test apart to look for potential manufacturing problems. Some products seemed slapdash, with pieces glued together, while others were too complex to be produced by the millions. “We saw tests that tried to shrink the whole lab, basically, in a very, very small form factor,” Dr. Brand said. “From an engineering point of view, amazing.” But, he added, “you cannot do that on scale.”Companies often adjusted their products in response to the scientists’ reports. The Atlanta team frequently “gave the key feedback to the companies that allowed them to change their platforms and make them really successful,” Dr. Tromberg said.By late 2020, several tests that had survived the Atlanta gauntlet had been authorized by the F.D.A., including the first at-home, over-the-counter Covid test, made by the Australian company Ellume.“We thought we were done,” Dr. Lam said. Then the Alpha variant took off: “We had to restart.”Variant vettingFrozen samples in an Emory biochemistry lab.Johnathon Kelso for The New York TimesA rapid antigen test from Maxim Biomedical containing an Omicron sample.Johnathon Kelso for The New York TimesCovid tests look for small pieces of the virus. Antigen tests, for instance, typically contain antibodies that bind to proteins, or antigens, on the virus’s surface.But mutations in the virus can change the shape of these proteins, making it harder for the antibodies to bind and generating false negatives. So in January 2021, the Atlanta researchers began working with the N.I.H. and F.D.A. to test dozens of authorized products against new variants. “At one point, we were testing 11 different variants,” Dr. Rao said. “Everyone was working all the time.”Laboratory experiments initially raised concerns about the sensitivity of some antigen tests for Omicron, but the tests appear to be performing better in the real world than they did in the lab, Dr. Lam said.The scientists are ready to repeat the process should a new variant pose a concern. “Like the National Guard,” Dr. Lam said. “They’re on reserve.”Since the fall, when the Biden administration announced plans to make at-home tests more accessible, the researchers have also been helping to speed F.D.A. authorization of products that can be produced in volume, including tests from Siemens and SD Biosensor.This work has been “crucial” said Dr. Michael Mina, a former Harvard epidemiologist who is now the chief science officer for eMed, which sells at-home tests. Typically, the onus is on test developers to collect their own data and navigate the regulatory process.But the Atlanta scientists and the federal government have created a better, more nimble model, he said — a systematic way for an independent party to vet products, ensuring their quality, and fast-track the approval of those that pass muster, getting them into consumers’ hands faster. “It sets a new approach that the U.S. could take in the evaluation of diagnostic tools,” Dr. Mina said.RADx has supported 29 manufacturers that have received 40 F.D.A. authorizations for Covid tests, including seven over-the-counter products, all of which have been evaluated by the Atlanta team.“Without a doubt the RADx program has accelerated the category of at-home diagnostics,” Dr. Sean Parsons, chief executive of Ellume, said in an email. “It has pushed innovation and development forward by years.”The next testsEric Ortlund, an Emory biochemist who is studying which future virus variants might evade detection with Covid tests.Johnathon Kelso for The New York TimesThe Atlanta scientists have also tackled basic research questions, such as whether children can reliably swab themselves (they can) and whether people should swab their throats instead of their noses (they should not).Some biochemists on the team are now forecasting the future. They developed a method for programming human cells to churn out viral antigens with every possible mutation. Each cell displays one version of this antigen, with one particular mutation, on its surface.Then, researchers can add one of the antibodies used in commercial tests to this collection of cells, along with a fluorescent marker that attaches to the antibody. The cells that give off the weakest fluorescent signals have not bound tightly to the antibody — indicating that they have mutations that will render the virus harder to detect with Covid tests that employ that antibody.“We can do binding experiments on all variants simultaneously,” said the Emory biochemist Eric Ortlund, brandishing a color-coded chart of how each possible mutation in one gene might affect the performance of a test that uses a given antibody. “They now have a map that will predict the impact of any mutation that may arise in the future.”The approach — which the team hopes to apply to other viruses, including influenza — could also help companies design more robust tests from the outset, selecting antibodies that are less likely to be rendered useless by a few small mutations.Some test manufacturers are already expanding their offerings; Ellume and Quidel, among others, have received N.I.H. funding to add flu detection to their antigen tests.And some of the technologies that didn’t make it to market, such as breath-based diagnostics, received feedback and investment that could speed their development, the Atlanta investigators said. “They might have now a head start for the next pandemic,” Dr. Brand said.Or, as Dr. Lam put it, “Think about all the things that came out of NASA trying to get to the moon.”

Supplies are more plentiful now but they are unpredictable and often a jumble of brands. Many places can’t meet the W.H.O.’s recommended dosing schedules.KAMAKWIE, Sierra Leone — In the tumbledown concrete room that has been commandeered as this sleepy African trading center’s Covid-19 vaccination headquarters, a battered freezer holds stacks of boxes with dozens of small glass vials.Stuffed among shots for rotavirus and measles are four brands of Covid vaccines. The vaccination team gives Sinopharm, donated from China, to the youngest and healthiest people because they’ve been told it’s the least effective of the vaccines, said Abdulai Conteh, who runs the operation. AstraZeneca, in which they have more faith, is normally just for people with underlying medical conditions. But the town recently received a big shipment that will expire soon, so the health workers are rushing to use it all up. Johnson & Johnson is given mostly to teachers, as a single shot.Rattling around in a salvaged carton tucked in a corner of the freezer are six vials that came in the last delivery — 36 shots of Pfizer, the most popular vaccination in the United States. That is the only Covid vaccine authorized here for people under 18, so in theory the heath workers try to save it for teenagers — but they also have to use up a vial once it’s open, so sometimes Pfizer is for whomever walks in the door.“More will be coming,” Mr. Conteh said. “We are not sure when.”The jumbled contents of the freezer, and the town’s improvised distribution strategy, are reflective of a new phase in the effort to vaccinate the world against Covid. Supply in the lowest-income countries is growing more plentiful, but it is often an unpredictable hodgepodge, arriving on an irregular schedule, making planning difficult. Underfunded health systems still lack the storage, personnel and transportation needed to carry out broad vaccination campaigns. Scientific understanding is continuously evolving about what it takes to achieve full and strong protection against existing and new Covid-19 variants. The United States and many wealthy countries have been pushing booster shots from Pfizer and Moderna, which use new technology seen as the gold-standard, in line with the latest thinking about the best chance for protection.But African countries continue to rely in part on products and dosing schedules that many researchers believe offer lower levels of protection, further clouding the prospect of stopping potential variants. Many are sticking with regimens that are no longer preferred by the World Health Organization, which developing countries look to for guidance on how and when to give Covid vaccines.In Sierra Leone, the Johnson & Johnson vaccine is still being used as a single shot, although the W.H.O. recommended in December that it should be given as two doses when possible.“What we say is, better one dose than zero,” Austin Demby, Sierra Leone’s health minister, said in an interview in the capital, Freetown. “And I would prefer two doses any time. But the logistics of it is just unbelievable. Imagine trying to track these multiple vaccinations, different dates, different times, different expiration dates. It’s a medley of protocols. It’s a nightmare.”Abdulai Conteh, right, the district health superintendent, loaded a cooler of vaccine doses for delivery at Kamakwie’s Covid vaccine headquarters.Finbarr O’Reilly for The New York TimesThe Pfizer vaccine, donated by the United States, is being delivered here as a two-shot regimen, not three, as it is in high-income countries. In January, the W.H.O. recommended booster shots of Pfizer’s vaccine, starting with the highest priority groups such as older people and health care workers.The two doses of the AstraZeneca shot are being delivered at erratic intervals, not the W.H.O.-recommended gap of eight to 12 weeks, because of difficulty tracking recipients, many of whom are subsistence farmers in rural areas.Sinopharm — the first Covid vaccine Sierra Leone received, through a gift from China early last year — has been found to produce a minimal immune response against the Omicron variant, even when given as three doses. Sierra Leone is giving it as two shots, with an often erratic dosing schedule.With Covid vaccination rates averaging about 14 percent across the continent, public health experts expect Africa to experience a fifth wave of the virus in the coming months, potentially from a new variant that could be more lethal. The target in Sierra Leone is to give primary immunizations to 40 percent of the population by June, but Dr. Demby acknowledged that this is hugely ambitious. Currently the figure is just 12 percent, and almost no one has received a booster shot.Here, as in the rest of West Africa, relatively few Covid cases or deaths have been recorded, likely as a result of a combination of poor reporting, limited testing and a younger population. The Omicron wave that hit the continent late last year drove an apparent spike in cases but not a surge in hospitalizations and deaths. As a result, there is less of a sense of urgency around vaccination.Dr. Denby, the health minister, said that after months of shortages, his country now has “a good stock” of Covid vaccines, but most people are preoccupied with the challenges of daily life, and have “no time whatsoever to go and stand in line for a vaccine.”His ministry has found that the best way to get people to accept a shot is to take it right to them, at churches and mosques, football matches or their doorsteps. But that is expensive. And it requires intensive staffing and diverting other resources away from polio vaccination and anti-malaria efforts that many here see as equal or greater priorities.Vaccine deliveries are now coming to Africa faster than many vaccination programs can get them into arms. Some African governments have had to ask manufacturers to pause shipments until they can use up what they have on hand. An African Union official said the bloc has effectively halted ordering more vaccines until countries can use a recent influx of donated doses from China and Covax, the clearinghouse that orders vaccines for poorer countries and delivers doses donated by other countries.About a quarter of the Covid vaccines that African countries have received have been the shots made by Pfizer and Moderna, which use newer messenger RNA technology, and have been regarded as the gold standard among Covid shots. (That figure omits instances in which the W.H.O. did not have data on which brand was delivered.) This year, the vast majority of the donations expected from the United States and Europe will be those two products.But as the mRNA products come into wider use in Africa, a debate has grown over whether those shots are optimal, both for the population being vaccinated and for stopping the emergence of variants and ending the pandemic.Christiana Dora Dumbuya, left, and Abdul K. Bangura, center, at a vaccination pop-up in Kathantha Yimbo. James S. Conteh, right, received a blue card documenting his first dose.Finbarr O’Reilly for The New York TimesThe shots from Pfizer and Moderna have consistently been found to perform better than vaccines using older technology, on different metrics of inducing immunity to the coronavirus. In particular, mRNA appears to offer the strongest short-term protection against Omicron. Some researchers expect this might well prove true with future variants as well.But the shots that use traditional vaccine technologies are easier to store and transport, and a mounting body of evidence shows that several may offer especially long-lasting protection across new variants, while the protection against infection offered by the Pfizer and Moderna has been found to fade faster over time.“Better means a few things,” Dr. Seth Berkley, the chief executive of Gavi, the main nonprofit behind Covax, in an interview from Geneva. “It obviously means high efficacy but it also means ease of use. It means cost effectiveness, it means duration of protection, and it means the ability to protect against different strains.”He added, “It may be that eventually mRNAs are the best vaccines — I don’t want to say that I know they’re not — but boy, do I not have any evidence that suggests now that they are the best vaccines.”For lower-income countries, non-mRNA shots and single-dose regimens still have an important role to play, said Katherine O’Brien, who directs the W.H.O.’s work on vaccines and immunizations. “Any vaccine that you can deliver is better than no vaccine that can be delivered,” she said.When given the option by the United States and Covax to choose which brand of donated vaccine they want, many lower-income countries have opted for products that have been spurned by rich countries. In Sierra Leone, as in other countries, the top preference is often Johnson & Johnson, because its ease of use as a single shot trumps all other factors.Last year, the W.H.O. called the push for boosters in rich countries morally indefensible when poor countries were facing severe supply shortages. But though those countries are still struggling to administer first doses widely, the agency has recently recommended additional shots for certain populations, and last week it endorsed boosters more emphatically than ever before.A booster shot can take different forms. It could be a second shot of any brand for a person who was initially immunized with a single dose of Johnson & Johnson’s vaccine. Or it could be a third shot — of any brand, but usually mRNA when possible — for someone who had already been fully vaccinated with two shots.When the United States donates doses, it encourages countries to both “double down on primary immunization, because the most important thing is that we get people that baseline of protection, but also make boosters available for people that are eligible,” said Hilary Marston, who leads the Biden administration’s vaccine donation program.Mr. Conteh in an office with freezers containing all types of Covid vaccines.Finbarr O’Reilly for The New York TimesBut in most African countries there is far too little of everything — vaccines, and all of the equipment and trained people it takes to administer them — to envision a significant booster campaign now.At the vaccine headquarters in Kamakwie, the health workers are just trying to figure out how to use the supplies they’ve been given as efficiently as possible. The health ministry, for instance, never instructed health workers to give Pfizer to teens and Johnson & Johnson to teachers, Dr. Demby, the health minister, said. Instead, the community came up with that patchwork rubric on its own. Many local officials have been hesitant to try to stimulate demand in the public, he said, not knowing what shots they will get and when.On a recent Tuesday, the vaccination team headed out with a small Styrofoam cooler of their mishmash of vaccines to the village of Kathantha Yimbo, about a 40 minute drive on a rough dirt track. An advance team had gone through with a motorbike and a bullhorn urging all those who had a vaccination card to turn up in the central square.About 40 people wandered in, but the cards of most showed they already had two Sinopharm shots. They were sent away, with no offers of boosters. Some people had one AstraZeneca, but it was delivered last June so the second shot they got that day came about six months later than the recommended eight to 12-week interval.Rugiatu Dumbuya, 35, who was selling fry cakes in the market, came to see what the excitement was about and decided to get her first vaccine, since the shots were right there. She had heard about Covid on a DVD of news reports a friend of hers purchased in town and played in the market recently. “I saw that people die of Covid sometimes, so I will take this even though I am not sure what it will do to me,” she said, just before she was given a Pfizer vaccine from the one vial the team brought.Mr. Conteh gave her a blue card recording her first vaccination and sent her on her way. No one discussed when — or if — she might get a second.Noah Weiland

Planned movement is essential to our daily lives, and it often requires delayed execution. As children, we stood crouched and ready but waited for the shout of “GO!” before sprinting from the starting line. As adults, we wait until the traffic light turns green before making a turn. In both situations, the brain has planned our precise movements but suppresses their execution until a specific cue (e.g., the shout of “GO!” or the green light). Now, scientists have discovered the brain network that turns plans into action in response to this cue.
The discovery, published in the scientific journal Cell, results from a collaboration of scientists at the Max Planck Florida Institute for Neuroscience, HHMI’s Janelia Research Campus, the Allen Institute for Brain Science, and others. Led by co-first authors Dr. Hidehiko Inagaki and Dr. Susu Chen and senior author Dr. Karel Svoboda, the scientists set out to understand how cues in our environment can trigger planned movement.
“The brain is like an orchestra,” said Dr. Inagaki. “In a symphony, instruments play diverse tunes with different tempos and timbres. The collective of these sounds shapes a musical phrase. Similarly, neurons in the brain are active with diverse patterns and timing. The ensemble of neuronal activities mediates specific aspects of our behavior.”
For example, the motor cortex is a brain area that controls movement. Activity patterns in the motor cortex are dramatically different between the planning and execution phases of movement. The transition between these patterns is critical to trigger movement. Yet, the brain areas controlling this transition were unknown. “There must be brain areas acting as the conductor,” described Dr. Inagaki. “Such areas monitor environmental cues and orchestrate neuronal activities from one pattern to the other. The conductor ensures that plans are converted into action at the right time.”
To identify the neural circuit that serves as the conductor to initiate planned movement, the team simultaneously recorded the activity of hundreds of neurons while a mouse performed a cue-triggered movement task. In this task, mice were trained to lick to the right if whiskers were touched or to the left if whiskers were not touched. If the animals licked in the correct direction, they received a reward. However, there was a catch. The animals had to delay their movement until a tone, or “go cue,” was played. Only correct movements after the go cue would be rewarded. Therefore, mice maintain a plan of the direction they will lick until the go cue and execute the planned lick after.
The scientists then correlated complex neuronal activity patterns to relevant stages of the behavioral task. The researchers found brain activity occurring immediately after the go cue and during the switch between motor planning and execution. This brain activity arose from a circuit of neurons in the midbrain, thalamus, and cortex.
To test whether this circuit acted as a conductor, the team used optogenetics. This approach enabled the scientists to activate or inactivate this circuit using light. Activating this circuit during the planning phase of the behavioral task switched the mouse’s brain activity from motor planning to execution and caused the mouse to lick. On the other hand, turning off the circuit while playing the go cue suppressed the cued movement. The mice remained in a motor planning stage as if they had not received the go cue.
This work by Dr. Inagaki and his colleagues identified a neural circuit critical for triggering movement in response to environmental cues. Dr. Inagaki explains how their findings demonstrate generalizable features of behavioral control. “We have found a circuit that can change the activity of the motor cortex from motor planning to execution at the appropriate time. This gives us insight into how the brain orchestrates neuronal activity to produce complex behavior. Future work will focus on understanding how this circuit and others reorganize neuronal activity across many brain regions.”
In addition to these fundamental advances in understanding how the brain functions, this work has important clinical implications. In motor disorders, such as Parkinson’s disease, patients experience difficulty in self-initiated movement, including difficulty in walking. However, adding environmental cues to trigger movements, such as lines on the floor or auditory tones, can dramatically improve a patient’s mobility. This phenomenon, known as paradoxical kinesia, suggests that different mechanisms in the brain are recruited for self-initiated movement and cue-triggered movement. Discovering the brain networks involved in cue-triggered movements, which are relatively spared in Parkinson’s disease, may help to optimize treatment.

Cognitive decline is the biggest factor in determining how long patients with Alzheimer’s disease will live after being diagnosed, according to a new study from researchers at UT Southwestern. The findings, published in the Journal of Alzheimer’s Disease, are a first step that could help health care providers provide reliable prediction and planning assistance for patients with Alzheimer’s disease and their families.
Using a National Alzheimer’s Coordinating Center dataset on 764 autopsy-confirmed cases, C. Munro Cullum, Ph.D., Professor of Psychiatry, Neurology, and Neurological Surgery, and first author Jeffrey Schaffert, Ph.D., a postdoctoral fellow in clinical neuropsychology at UT Southwestern, identified seven factors that helped predict life expectancy variances among participants. These factors are the most predictive of how many years of life remain after diagnosis.
“Life expectancy for patients with Alzheimer’s disease typically ranges from three to 12 years but can be longer in some cases. Families are anxious to know what to expect and how to best plan for the time ahead in terms of finances, family caregiving, and how they want to live out their lives,” said Dr. Cullum, a neuropsychologist Investigator in the Peter O’Donnell Jr. Brain Institute who specializes in cognitive assessment. “We’re trying to get them better answers.”
Of the many variables studied, performance deficiencies on a brief cognitive screening test that focuses on orientation was the most significant predictor, accounting for about 20% of the variance in life expectancy. This was followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings.
“We found that beyond global cognitive function, patients who were older, non-Hispanic, male, and who had more motor and psychiatric symptoms had a significantly shorter life expectancy,” Dr. Schaffert said.
The data was drawn from clinical records and autopsy reports on patients who died with Alzheimer’s disease between 2005 and 2015. Alzheimer’s disease was confirmed by traditional abnormalities observed in brain autopsy specimens, including the presence of abnormal protein aggregation. Life expectancy in the study group ranged from one month to 131 months after diagnosis, and most were diagnosed on their first visit.
Dr. Schaffert explained that past studies have focused on only a few of the 21 predictors identified for life expectancy. In this case, researchers had a complete dataset for 14 variables in this group, the largest to date. Moreover, past studies have not been autopsy-based, thereby confounding results with data from other forms of dementia that mimic Alzheimer’s disease.
The researchers caution that prediction of life expectancy is complex and influenced by many factors. While the cognitive test used in the study was a relatively strong predictor, they plan to follow up using more sensitive measures of memory and other specific cognitive abilities as predictors and probe how the rate of decline in cognition may track with life expectancy. They also hope to expand the population base.
“This dataset was largely derived from well-educated white patients who donated their brains to research. We would like to extend this work to better reflect our more diverse patient population,” Dr. Cullum said.
This study was supported by the Texas Alzheimer’s Research and Care Consortium (TARCC), funded by the state of Texas through the Texas Council on Alzheimer’s Disease and Related Disorders, and by the Texas Institute for Brain Injury and Repair (TIBIR), a state-funded initiative as part of the O’Donnell Brain Institute. Dr. Cullum is TARCC’s Scientific Director.
Dr. Cullum holds the Pam Blumenthal Distinguished Professorship in Clinical Psychology.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesThe transport secretary has confirmed that all remaining Covid travel measures will be scrapped.Currently, everyone travelling to the UK must complete a passenger locator form before they arrive. Travellers who are not fully vaccinated have to take a Covid test before departure, fill in the form, and book and pay for a PCR test after arriving. Grant Shapps confirmed in a tweet that these rules will end at 04:00 on Friday.His announcement means that passengers who are not fully vaccinated will no longer have to take Covid tests before and after travelling to the UK. The passenger locator form will no longer be necessary either.People planning an overseas trip will still need to be aware of other countries’ entry rules. Mr Shapps tweeted: “These changes are possible due to our vaccine rollout and mean greater freedom in time for Easter.”When any new Covid strains appear in the future, the government said its default approach would be to use “the least-stringent measures” for restricting travel.Its “Living with Covid” plan said new measures at the border would only be considered in “extreme circumstances”. It said the UKHSA would closely monitor the prevalence and spread of Covid variants.What are the UK’s ‘Living with Covid’ plans? Scotland and Wales have agreed to follow England in scrapping the remaining coronavirus border measures.But Welsh Health Minister Eluned Morgan said she was doing so “reluctantly” – and was “extremely disappointed” that testing requirements and the passenger location form were being ditched.The Scottish government said consistency across the four nations was agreed because of the “negative impact of non-alignment on the tourism industry”.Testing requirements for fully-vaccinated arrivals into the UK were dropped in February. The latest move was welcomed by some figures in the travel industry, which has campaigned for the remaining rules to be dropped so businesses can take full advantage of strong summer holiday demand.Tim Alderslade, chief executive of trade body Airlines UK, said: “Today’s announcement sends a clear message to the world – the UK travel sector is back. “With travellers returning to the UK no longer burdened by unnecessary forms and testing requirements, we can now look forward to the return to pre-Covid normality throughout the travel experience.”A Virgin Atlantic spokesperson said: “The removal of all remaining UK travel restrictions is the final important step towards frictionless air travel, helping to further restore consumer confidence as we welcome more customers back to the skies this spring and summer. “To uphold the experience of all travellers, it’s vital that the UK Government works closely with industry to ensure the UK border is ready for increasing passengers, as international travel ramps up.”Meanwhile, Eurostar’s chief executive Jacques Damas said the easing of restrictions would help the cross-Channel train operator’s recovery.”We hope and expect to see the UK’s approach replicated across our other markets in the coming weeks,” Mr Damas said.Challenges remainHowever, as Covid restrictions recede, other headwinds for the aviation industry are appearing.The price of jet fuel has soared as a result of higher crude oil prices. This adds to cost pressures on airlines, although some have been protected by their hedging strategies, whereby they purchased fuel in advance at lower prices.On Friday, the chief executive of Heathrow airport, John Holland-Kaye, said the recovery of aviation remained “overshadowed by war and Covid uncertainty”.Businesses will also be keeping a careful eye on whether consumers’ confidence to book is knocked by the war in Ukraine and rising household bills squeezing disposable incomes. Air France-KLM and Ryanair have both recently warned air fares will rise.More on this storyWhat are the UK’s ‘Living with Covid’ plans?Ryanair boss: Air fares will be higher this summerWhat Covid rules do holiday destinations have?

A new study suggests that the malaria drug hydroxychloroquine inhibits pathways that drive resistance to the chemotherapy agent cisplatin in head and neck cancers and restores tumor-killing effects of cisplatin in animal models.
The findings, published today in Proceedings of the National Academy of Sciences by University of Pittsburgh and UPMC scientists, pave the way for a clinical trial that combines cisplatin and hydroxychloroquine to treat chemotherapy-resistant head and neck cancers.
“When caring for patients with head and neck cancers, I often see chemotherapy fail. Cisplatin is a very important chemotherapy drug, but tumor resistance to cisplatin is a huge problem,” said co-senior author Umamaheswar Duvvuri, M.D., Ph.D., head and neck surgeon at UPMC Hillman Cancer Center and professor of otolaryngology in Pitt’s School of Medicine. “My lab is interested in understanding the mechanisms of resistance so that we can find better ways to treat these patients.”
Previous research showed that a protein called TMEM16A is linked with cisplatin resistance in patient tumors. Overexpression of this protein, which occurs in about 30% of head and neck cancers, is also associated with decreased survival.
TMEM16A belongs to a group of proteins called ion channels. Straddling the cell’s outer envelope, these proteins provide a passageway to chloride ions, which regulate muscle and nerve activation and transport of salt and water. Because impaired chloride transport is typically linked with neurological and kidney diseases such as epilepsy, cystic fibrosis and kidney stones, Duvvuri was surprised by the link between TMEM16A and cancer.
“It’s always been a bit of a puzzle as to why an ion channel is upregulated in cancer,” he said. “This research provides important clues towards solving this puzzle.”
The new study suggests that TMEM16A promotes expulsion of cisplatin in cellular compartments called lysosomes. In a healthy cell, lysosomes act like a recycling and waste disposal system, breaking down molecules for reuse and expelling cellular detritus.

Close the blinds, draw the curtains and turn off all the lights before bed. Exposure to even moderate ambient lighting during nighttime sleep, compared to sleeping in a dimly lit room, harms your cardiovascular function during sleep and increases your insulin resistance the following morning, reports a new Northwestern Medicine study.
“The results from this study demonstrate that just a single night of exposure to moderate room lighting during sleep can impair glucose and cardiovascular regulation, which are risk factors for heart disease, diabetes and metabolic syndrome,” said senior study author Dr. Phyllis Zee, chief of sleep medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “It’s important for people to avoid or minimize the amount of light exposure during sleep.”
There is already evidence that light exposure during daytime increases heart rate via activation of the sympathetic nervous system, which kicks your heart into high gear and heightens alertness to meet the challenges of the day.
“Our results indicate that a similar effect is also present when exposure to light occurs during nighttime sleep,” Zee said.
The study will be published March 14 in PNAS.
Heart rate increases in light room, and body can’t rest properly
“We showed your heart rate increases when you sleep in a moderately lit room,” said Dr. Daniela Grimaldi, a co-first author and research assistant professor of neurology at Northwestern. “Even though you are asleep, your autonomic nervous system is activated. That’s bad. Usually, your heart rate together with other cardiovascular parameters are lower at night and higher during the day.”

Having dense breasts (more fibroglandular tissue than fatty tissue, as visualized on a mammogram) reduces the sensitivity of mammography by masking breast cancers and carries a 1.6- to 2.0-fold increased independent risk for breast cancer. To inform women about these risks, 38 U.S. states and the federal government have enacted legislation requiring a written dense breast notification (DBN) of a patient’s breast density after a mammogram, but there still is limited evidence about what breast density means, and what the implications are, to women.
According to a new study, while women are receiving these notifications about their breast density, not all recipients are fully understanding what they mean in terms of future health implications. Boston University School of Medicine researchers suggest that knowledge about breast density and its associated risks is partly linked to women’s race/ethnicity and health literacy.
“Our findings, together with prior reports suggest that DBNs alone are not adequately educating women, suggest that development of future notifications warrants further refinement and testing,” says corresponding author Nancy Kressin, PhD, professor of medicine at BUSM.
To assess women’s knowledge about breast density after receiving a notification, the researchers conducted a telephone survey and interviews among a racially/ethnically and health literacy level diverse sample. Although most women responded correctly that breast density is related to the amount of fatty versus connective tissue, the researchers observed significant variations by women’s race/ ethnicity, whereby Non-Hispanic White women were less likely to respond correctly than Non-Hispanic Black women.
Only 47 percent of women correctly indicated that having dense breasts increases one’s risk of breast cancer; women with low health literacy were more often correct. Fifty-eight percent of women correctly indicated that breast density is not related to touch, with higher accuracy among non-Hispanic white women and those with greater health literacy. Eighty-seven percent of women recognized that breast density is identified visually via mammogram, with no significant differences in responses by race/ethnicity or health literacy.
Qualitative results revealed additional dimensions of understanding: Some women incorrectly reported that density could be felt, or dense breasts were lumpier, thicker, or more compacted; others identified ”dense” tissue as fatty. Interpretations of risk included that breast density was an early form of breast cancer.
“The ultimate goal of DBNs is to educate women about breast density, to guide their future decisions about breast cancer screening. Thus, in-depth characterization of women’s knowledge after receiving a DBN can help ensure that future health communications are accessible and understandable to all recipients,” adds Kressin.
These findings appear online in the Journal of Women’s Health.
Funding for this study was provided by a grant from the American Cancer Society (133017-RSG-19-085-01-CPHPS); C.M.G. was also supported by the National Cancer Institute (1K07CA221899).
P.J.S., Co-author on an UpToDate article on Breast density and screening for breast cancer, for which she receives royalties.
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Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.