Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.
Complex interplay: the gut-immune-brain axis
The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. “We investigated the role this axis plays in the brain development of extreme preterm infants,” says the first author of the study, David Seki. “The microorganisms of the gut microbiome — which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes — are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain,” explains the microbiologist and immunologist.
Patterns in the microbiome provide clues to brain damage
“In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”
Comprehensive study of the development of extremely premature infants
Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. “Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage,” explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. “We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods — the team examined the microbiome using 16S rRNA gene sequencing, among other methods — the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.
Research continues with two studies
The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika Berger. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. ” The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”
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Individuals who are hospitalized during pregnancy due to sepsis have higher odds of complications surrounding childbirth, according to a study led by researchers at UC San Francisco. The study found that pregnancies complicated by sepsis were associated with an increased risk of cesarean delivery, postpartum hemorrhage and preterm delivery, highlighting the risk of any severe infection during pregnancy.
“If pregnant women were admitted for severe infection, even after they’re discharged and they recover from that infection, there was an increased risk of complications related to pregnancy that are associated with core placental dysfunction,” said Stephanie Gaw, MD, PhD, assistant professor of Obstetrics, Gynecology & Reproductive Sciences at UCSF, and senior author of the paper, which appears September 3, 2021, in JAMA Network Open.
Sepsis is a life-threatening condition caused by an unusually severe response to an infection, which leads to widespread inflammation in the body and, potentially, organ failure and death. Maternal sepsis is the second leading cause of maternal mortality in the United States, according to the Centers for Disease Control and Prevention (CDC).
The timing of infection also impacts outcomes for mother and baby. The cohort study found that patients with sepsis before delivery were twice as likely to have placental dysfunction compared to pregnant patients without sepsis.
During the study, the mean gestational age at the time of infection was 24.6 weeks. Early infection, at less than 24 weeks of gestation, was associated with the greatest risk of placental dysfunction, maternal hypertensive disorder, and newborns who were small for gestational age.
Downstream Consequences of COVID or Other Infections
Although the study used pre-pandemic data, Gaw says the findings are an important reflection of the potential long-term consequences of any acute infection.

Researchers from Kaunas universities, Lithuania developed a deep learning-based method that can predict the possible onset of Alzheimer’s disease from brain images with an accuracy of over 99 per cent. The method was developed while analysing functional MRI images obtained from 138 subjects and performed better in terms of accuracy, sensitivity and specificity than previously developed methods.
According to World Health Organisation, Alzheimer’s disease is the most frequent cause of dementia, contributing to up to 70 per cent of dementia cases. Worldwide, approximately 24 million people are affected, and this number is expected to double every 20 years. Owing to societal ageing, the disease will become a costly public health burden in the years to come.
“Medical professionals all over the world attempt to raise awareness of an early Alzheimer’s diagnosis, which provides the affected with a better chance of benefiting from treatment. This was one of the most important issues for choosing a topic for Modupe Odusami, a PhD student from Nigeria,” says Rytis Maskeli?nas, a researcher at the Department of Multimedia Engineering, Faculty of Informatics, Kaunas University of Technology (KTU), Odusami’s PhD supervisor.
Image processing delegated to the machine
One of the possible Alzheimer’s first signs is mild cognitive impairment (MCI), which is the stage between the expected cognitive decline of normal ageing and dementia. Based on the previous research, functional magnetic resonance imaging (fMRI) can be used to identify the regions in the brain which can be associated with the onset of Alzheimer’s disease, according to Maskeli?nas. The earliest stages of MCI often have almost no clear symptoms, but in quite a few cases can be detected by neuroimaging.
However, although theoretically possible, manual analysing of fMRI images attempting to identify the changes associated with Alzheimer’s not only requires specific knowledge but is also time-consuming — application of Deep learning and other AI methods can speed this up by a significant time margin. Finding MCI features does not necessarily mean the presence of illness, as it can also be a symptom of other related diseases, but it is more of an indicator and possible helper to steer toward an evaluation by a medical professional.

By developing the first statistical model to finely characterize how ketamine anesthesia affects the brain, a team of researchers at MIT’s Picower Institute for Learning and Memory and Massachusetts General Hospital have laid new groundwork for three advances: understanding how ketamine induces anesthesia; monitoring the unconsciousness of patients in surgery; and applying a new method of analyzing brain activity.
Based on brain rhythm measurements from nine human and two animal subjects, the new model published in PLOS Computational Biologydefines the distinct, characteristic states of brain activity that occur during ketamine-induced anesthesia, including how long each lasts. It also tracks patterns of how the states switch from one to the next. The “beta-hidden Markov model” therefore provides anesthesiologists, neuroscientists, and data scientists alike with a principled guide to how ketamine anesthesia affects the brain and what patients will experience.
In parallel work the lab of senior author Emery N. Brown, an anesthesiologist at MGH and Edward Hood Taplin Professor of Computational Neuroscience at MIT, has developed statistical analyses to characterize brain activity under propofol anesthesia, but as the new study makes clear, ketamine produces entirely different effects. Efforts to better understand the drug and to improve patient outcomes therefore depend on having a ketamine-specific model.
“Now we have an extremely solid statistical stake in the ground regarding ketamine and its dynamics,” said Brown, a professor in MIT’s Department of Brain and Cognitive Sciences and Institute for Medical Engineering & Science, as well as at Harvard Medical School.
Making a model
After colleagues at MGH showed alternating patterns of high-frequency gamma rhythms and very low-frequency delta rhythms in patients under ketamine anesthesia, Brown’s team, led by graduate student Indie Garwood and postdoc Sourish Chakravarty set out to conduct a rigorous analysis. Chakravarty suggested to Garwood that a hidden Markov model might fit the data well because it is suited to describing systems that switch among discrete states.

The development of direct-acting antiviral (DAA) agents revolutionized treatment for the hepatitis C virus (HCV) in 2013, changing the disease from one that can be controlled to one that can be cured. But with a list price of $25,000 to $95,000 per prescription, state Medicaid programs — which insure a disproportionate number of people with HCV — have imposed strict limitations on who can qualify for these medications.
Subscription-based payment models (SBPM), a novel approach in which states contract exclusively with a single manufacturer to supply prescriptions at a reduced price, could increase access to these life-saving treatments, according to a new School of Public Health study. In a SBPM, states pay reduced per prescription prices for medications until a certain utilization threshold. After this threshold, the cost of additional prescriptions is essentially zero.
Published in the journal JAMA Health Forum, the study examined changes in Medicaid-covered HCV prescription fills in Louisiana and Washington after the two states implemented SBPMs in July 2019. While Washington did not experience a significant change in quarterly HCV prescription fills, Louisiana’s prescription fills increased by 534 percent.
“With subscription-based payment models, there’s no incentive to ration access because there is almost no cost of additional prescriptions after the threshold,” says study lead author Samantha Auty, a doctoral candidate in the Department of Health Law, Policy & Management. “This model actually incentivizes states to treat as many individuals who would benefit from HCV treatment as possible, which improves population health in a group of individuals who face structural barriers to care and aligns with the goals of the WHO to eradicate this virus by 2030.”
For the study, Auty and colleagues used publicly available Medicaid data from all 50 states and Washington, DC to compare changes in HCV prescription fills between the two states that implemented SBPMs and those that did not. The average rate of HCV prescription fills per 100,000 Medicaid enrollees rose from 43.1 to 206.0 in Louisiana and from 50.1 to 53.9 in Washington.
The researchers say the differences in increased medication use between the two states may be explained by state variation in SBPM implementation, differences in the populations that qualified for HCV medication coverage prior to SBPMs in each state, and screening and treatment delays as a result of the COVID-19 pandemic. Louisiana lifted its liver damage and sobriety restrictions for HCV medication access simultaneously with SBPM adoption, while Washington removed these restrictions in 2016. Even when accounting for this change, Louisiana experienced an 180.2% increase in HCV prescription use following SBPM adoption.
SBPMs are similar to the advance market commitment that the US adopted for its COVID vaccination strategy, in which the country pledged to purchase high-cost vaccines from select manufacturers, says Auty. The SBPM model appears to be a scalable solution that other states could apply to multiple public health issues, she says.
“Our results are evidence that SBPMs can work, and there are other epidemics in the US that could benefit from this type of model,” Auty says. “Medications for opioid use disorder saves many lives, as they reduce risk of overdose, death, and other comorbidities related to use. My hope is that these results provide support for the use of SBPMs not just for HCV, but for other high-value medications as well.”
The study was co-authored by Paul Shafer, assistant professor of health law, policy & management, and Kevin Griffith, SPH alum and assistant professor of policy at Vanderbilt University Medical Center.
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Materials provided by Boston University School of Medicine. Original written by Jillian McKoy. Note: Content may be edited for style and length.

Scientists from the Faculty of Engineering, Information, and Systems at the University of Tsukuba analyzed video from top-level judo matches to systematically determine the aspects of posture, just before executing a throw, that lead to success. This work may help in quantitative measurements of other biomechanical processes, as well as improving coaching methods.
Many athletic training regimens use repetition to perfect technique. However, seeing the difference between correct and improper form can often require the keen eye of an experienced coach or trainer. Having an automated method that can detect the body movements that correlate with successful outcomes would be of great assistance to newcomers and professionals alike. Now, scientists from the University of Tsukuba have developed a computer method that uses video from real competitions, including the Judo World Championships, to better understand the key aspects of grabbing and throwing one’s opponent. Using this approach, the critical factors of the body positioning just before a successful throw can be identified.
“We can develop a new training method for athletes to master the most successful throwing techniques if we can find the correlations among the postures right before initiating a throw,” author Professor Shinichi Yamagiwa says. This process had two main phases, the measurement phase and analysis phase. First, the team collected video from 781 successful judo throws. Then, they used a χ2 statistical test to identify the aspects of the situation that correlated with success. To explain the results of the paper, the authors describe two judoka, or judo practitioners, named Tori and Uke. In these illustrations, Tori is executing a throw of Uke. “We found that Uke’s distance from Tori’s shoulders and legs is key to correct throwing technique,” Professor Shinichi Yamagiwa says.
Future training systems using the method may include graphical interfaces to work with videos.This is particularly useful for self-training systems for martial arts.
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The common analogy for CRISPR gene editing is that it works like molecular scissors, cutting out select sections of DNA. Stanley Qi, assistant professor of bioengineering at Stanford University, likes that analogy, but he thinks it’s time to reimagine CRISPR as a Swiss Army knife.
“CRISPR can be as simple as a cutter, or more advanced as a regulator, an editor, a labeler or imager. Many applications are emerging from this exciting field,” said Qi, who is also an assistant professor of chemical and systems biology in the Stanford School of Medicine and a Stanford ChEM-H institute scholar.
The many different CRISPR systems in use or being clinically tested for gene therapy of diseases in the eye, liver and brain, however, remain limited in their scope because they all suffer from the same flaw: they’re too large and, therefore, too hard to deliver into cells, tissues or living organisms.
In a paper published Sept. 3 in Molecular Cell, Qi and his collaborators announce what they believe is a major step forward for CRISPR: An efficient, multi-purpose, mini CRISPR system. Whereas the commonly used CRISPR systems — with names like Cas9 and Cas12a denoting various versions of CRISPR-associated (Cas) proteins — are made of about 1000 to 1500 amino acids, their “CasMINI” has 529.
The researchers confirmed in experiments that CasMINI could delete, activate and edit genetic code just like its beefier counterparts. Its smaller size means it should be easier to deliver into human cells and the human body, making it a potential tool for treating diverse ailments, including eye disease, organ degeneration and genetic diseases generally.
Persistent effort
To make the system as small as possible, the researchers decided to start with the CRISPR protein Cas12f (also known as Cas14), because it contains only about 400 to 700 amino acids. However, like other CRISPR proteins, Cas12f naturally originates from Archaea — single-celled organisms — which means it is not well-suited to mammalian cells, let alone human cells or bodies. Only a few CRISPR proteins are known to work in mammalian cells without modification. Unfortunately, CAS12f is not one of them. This makes it an enticing challenge for bioengineers like Qi.

SharecloseShare pageCopy linkAbout sharingimage sourceGetty ImagesIsrael’s booster vaccination programme – offering a third shot to over-40s – has begun to show signs of success.But the country’s recent spike in cases has ignited debate about the future of the vaccination programme and the ongoing pandemic.It had virtually returned to normal life by this spring, cases stayed low and it looked like vaccination had more or less quashed Covid. From July, though, cases started to rise again. Since Israel surged ahead in immunising its population last winter, the rest of the vaccinated world has turned to it to understand what might be in store in the coming weeks and months. The country’s own health leaders will be keeping a watchful eye on cases after schools reopened on 1 September, while next week, Rosh Hashanah, the Jewish new year, will see groups gathering. Unvaccinated peopleAlthough the country rolled out jabs quickly and take-up was relatively high, there are still a million people out of its roughly nine million overall population who are eligible for the vaccine and haven’t taken it up.Israel is also a relatively young country, with about a third of its population under the age of 14. Under-12s are not eligible for the vaccine unless they have particular health conditions. That means, despite high take-up, only 60% of the total population is fully vaccinated with two doses.But even without these groups being vaccinated, back in spring the level of coverage appeared to be enough to keep a lid on cases – so what changed?Waning immunityThe more infectious Delta variant seems to have evaded part of the vaccine’s protection against infection, although it is still highly effective against severe illness. But scientists monitoring the data believe a major factor in the recent spike in cases is waning immunity from the Pfizer vaccine, which was initially the only one given in the country. Prof Eran Segal, who advises the Israeli government on Covid matters, said by month five or six after vaccination, people are probably only 30-40% protected, compared with more than 90% when protection first kicks in. “That’s what was driving the wave,” he said – a conclusion drawn from careful analysis of the rates of infection in people vaccinated in different months. Despite this fall, vaccination still prevents a substantial amount of sickness, with the unvaccinated becoming severely ill with Covid about nine times as often in over-60s, and twice as often in younger people. A third vaccination?Israel is responding to the dip in protection against infection by rolling out a booster programme, offering a third jab first to over-60s and more recently to the over-40s. The boosters for older people began to be offered just over a month ago, and they appear to be now taking effect, with hospital admissions levelling off in that group.”This is leading to a halt in the Delta wave,” Prof Segal said. Early data suggests a tenfold increase in protection from infection and severe disease after the third jab, compared with after two. Dr Anat Ekka Zohar, who is leading the booster programme study, said three doses were “highly protective, against both infection and severe illness”. She added: “The triple dose is the solution to curbing the current infection outbreak.” So what’s next?There are fierce debates over whether booster programmes should be rolled out when so many people around the world haven’t even had one vaccine.And some have questioned whether it is sustainable to top up the vaccines every six months, or once a year as is the case with the flu jab. While we’ve built up a large amount of evidence to show the Covid vaccines are safe and effective for almost everyone, there are still areas where we need more information. One of those areas is exactly how long immunity lasts, and whether a third booster shot will provide much more durable protection. It could be that a three-shot schedule is what’s needed, as in the case of the hepatitis B vaccine, where three doses result in more or less lifelong protection for most.Or it could be that two jabs plus natural immunity will be enough. People can get good natural protection after catching the virus, but, without a vaccine, that comes with the risk of becoming very ill, developing long-term complications or dying. With the vaccines now protecting against most of the worst disease, people may still catch milder versions of Covid and boost their vaccine-derived immunity that way. Scientists have hypothesised that repeated exposure to the Covid infection, now with the protection of the vaccine and natural immunity from past infection rendering it less risky, could over time turn the virus into a potentially recurring, but relatively untroublesome illness.What’s the best way to top up our Covid immunity?But others fear there may be a high cost to this, as breakthrough infections can still reach the most vulnerable and the eventual toll of “long Covid” remains unknown. At the least, Israel’s booster programme might provide more answers to some of these remaining questions.

What to Know: Purdue Pharma SettlementJan HoffmanReporting on the opioid epidemicAbout 130,485 people who can prove they were harmed by OxyContin will each get between $3,500 and $48,000. Guardians of 6,550 children born with symptoms of opioid withdrawal will receive about $7,000. Over the past 20 years, more than 500,000 people in the U.S. died from prescription and illicit opioids. Federal economists said that the true cost of the epidemic — including law enforcement, healthcare and treatment — could run into trillions of dollars. During the pandemic, overdose deaths soared.

Federal regulators warned on Thursday they may not have enough data to recommend boosters for anyone except certain recipients of the Pfizer vaccine by late September.WASHINGTON — Top federal health officials have told the White House to scale back a plan to offer coronavirus booster shots to the general public later this month, saying that regulators need more time to collect and review all the necessary data, according to people familiar with the discussion.Dr. Janet Woodcock, the acting commissioner of the Food and Drug Administration, and Dr. Rochelle P. Walensky, who heads the Centers for Disease Control and Prevention, warned the White House on Thursday that their agencies may be able to determine in the coming weeks whether to recommend boosters only for recipients of the Pfizer-BioNTech vaccine — and possibly just some of them to start.The two health leaders made their argument in a meeting with Jeffrey D. Zients, the White House pandemic coordinator. Several people who heard about the session said it was unclear how Mr. Zients responded. But he has insisted for months that the White House will always follow the advice of government scientists, wherever it leads.Asked about the meeting, a White House spokesman on Friday said, “We always said we would follow the science, and this is all part of a process that is now underway,” adding that the administration was awaiting a “full review and approval” of booster shots by the F.D.A. as well as a recommendation from the C.D.C.“When that approval and recommendation are made,” the spokesman, Chris Meagher, said, “we will be ready to implement the plan our nation’s top doctors developed so that we are staying ahead of this virus.”Less than three weeks ago, Mr. Biden said that contingent on F.D.A. approval, the government planned to start offering boosters the week of Sept. 20 to adults who had received their second shot of the Pfizer-BioNTech or Moderna vaccine at least eight months ago. That would include many health care workers and nursing home residents, as well as some people older than 65, who were generally the first to be vaccinated. Administration officials have said that recipients of the single-dose Johnson & Johnson vaccine would probably be offered an additional shot soon as well.Mr. Biden cast the strategy as another tool that the nation needed to battle the highly contagious Delta variant, which has driven up infection rates, swamped hospitals with Covid-19 patients and is now leading to an average of more than 1,500 deaths a day. “The plan is for every adult to get a booster shot eight months after you got your second shot,” he said on Aug. 18, adding, “It will make you safer, and for longer. And it will help us end the pandemic faster.”Like Mr. Biden, members of his pandemic response team have said that the plan depended on the F.D.A. and the C.D.C. authorizing the booster shots. Both Dr. Woodcock and Dr. Walensky publicly endorsed the strategy, as did the nation’s other senior health leaders.Privately, Dr. Woodcock had argued that it was risky to set a firm date for a booster rollout before regulators had a chance to thoroughly review the data, some of which had yet to be submitted by the vaccine manufacturers, and decide whether shots were safe and necessary, according to several people familiar with the discussions.And since the White House announced the booster plan in mid-August, they said, new hurdles appeared.Among the reasons for delaying is that regulators need more time to decide the proper dosage for a possible third Moderna shot. The company’s application asking the F.D.A. to authorize a booster shot contains insufficient data, one federal official familiar with the process said. Other data expected from Johnson & Johnson has not been delivered.Nor has the raw data that the F.D.A. has been seeking from Israel, which is already giving boosters to everyone 12 and older. Israeli officials say their data shows that the potency of Pfizer’s vaccine wanes over time against severe disease and hospitalization, but that a third shot bolsters protection significantly. The F.D.A. wants to see the underlying data, to make sure it backs up summaries that the Israeli government has provided.Dr. Janet Woodcock, the acting commissioner of the Food and Drug Administration, has privately argued that setting a firm date for booster shots to begin was risky.Stefani Reynolds for The New York TimesNarrowing the booster plan could confuse the public and create a perception that federal vaccine policy is in some degree of disarray. But some public health experts will most likely welcome it.They have been arguing strenuously that the administration lacks the data to justify a broad rollout of extra shots and should instead concentrate on vaccinating the roughly 25 percent of Americans who are eligible for shots but remain unprotected. And some have said that Biden aides wrongly cornered regulators by announcing a strategy before they could conduct a full review..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{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;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{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;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{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-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}Regulators are only beginning to review critical data that will help them determine if and how boosters should be given. Pfizer completed its booster application to the F.D.A. last week, officials said, and Moderna has just initiated its own.This week, two of the F.D.A.’s top vaccine regulators announced that they would be leaving the agency this fall, apparently partly because of frustration with the administration’s booster plan. Dr. Marion Gruber, who directs the agency’s vaccines office, and her deputy, Dr. Philip Krause, have told people there was not nearly enough data to justify offering extra shots to the general population starting in just weeks.More friction may lie ahead. On Sept. 17, the F.D.A.’s outside advisory committee is scheduled to publicly review Pfizer’s data supporting a booster shot. Even though Pfizer has asked the F.D.A. to approve booster doses for people 16 and up, the agency could decide to restrict who gets a booster. The C.D.C. and its outside advisory panel would also have to weigh in.One key member of the F.D.A.’s advisory panel, Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, argues boosters are premature. “There is no compelling reason to get a third dose” now, he said in an interview on Thursday.He said the administration had appeared to expect that the F.D.A. and the C.D.C. would rubber-stamp its booster timeline. “Bypassing and marginalizing those agencies led veterans who you need in this pandemic to leave the F.D.A.,” he said, referring to the departures of Dr. Gruber and Dr. Krause.Various studies have shown that the potency of the Pfizer-BioNTech and Moderna vaccines ebbs against infection over time, but suggest that the vaccines continue to offer robust protection against severe illness and hospitalization.But Dr. Vivek Murthy, the surgeon general, said in an interview on Thursday that a few studies have suggested a dip in protection against severe disease over time. “Our feeling was that if we waited several more months we would see protection against hospitalizations and deaths break down,” he said.In an interview published Thursday on WebMD.com, Dr. Woodcock echoed that view, saying that the trend of breakthrough infections has led health officials to believe at some point, “we are going to see hospitalizations and more serious disease” among fully vaccinated people. When that happens, she said, “we want to be ready” with the booster plan.Some Americans are already getting booster shots ahead of F.D.A. approval: more than a million fully vaccinated people have received an additional dose since mid-August.