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A type of glaucoma called normal-tension glaucoma is associated with an increased risk of cognitive impairment and possibly dementia, finds research published online in the British Journal of Ophthalmology.
Glaucoma is a condition in which the optic nerve becomes damaged and this can eventually lead to blindness. In most types of glaucoma, the damage is caused by a build-up of pressure in the eye, but this is not the case with normal-tension glaucoma.
The disease pathway for normal-tension glaucoma — a subtype of primary open angle glaucoma (POAG) — is not fully understood, but the authors say their findings suggest that it may share similar neurodegenerative pathways with dementia.
Primary open angle glaucoma and dementia have been linked in some previous studies, but not all studies have found this association.
Primary open angle glaucoma encompasses not only low-tension glaucoma or normal-tension glaucoma (NTG), where the pressure in the eye is not raised above normal levels, but also high-tension glaucoma (HTG), where pressure in the eye is high. Normal-tension glaucoma is more common in Asia, while high-tension glaucoma is more common in Europe.
Two of the studies which showed a link between primary open angle glaucoma and dementia included lots of people with Asian ethnicity. This led the authors to wonder whether it may be specifically normal-tension glaucoma that is linked to cognitive impairment and dementia.
To investigate, they used the Australian and New Zealand Registry of Advanced Glaucoma to randomly select 248 patients aged at least 65 years who had normal-tension glaucoma, and these were matched by age and sex with 349 patients with high-tension glaucoma.
All patients were invited to participate in a health questionnaire and cognitive assessment over the telephone. A total of 290 patients — 144 with normal-tension glaucoma and 146 with high-tension glaucoma — had the cognitive screen. There was no difference between the two groups in demographic and eye parameters at baseline.
Cognitive impairment was found to be more than twice as prevalent in patients with normal-tension glaucoma than it was in those with high-tension glaucoma.
This is an observational study, so can’t establish cause, and the authors cannot rule out the possibility that results were affected by unobserved differences in clinical features or cognition of patients who could not be contacted or did not participate.
And while cardiovascular disease risk factors strongly associated with dementia, such as stroke, smoking, high blood pressure and diabetes were accounted for in the analysis, other potentially influential factors, such as socioeconomic status were not.
Nevertheless, the authors conclude: “Our finding of an association between normal-tension glaucoma and cognitive impairment supports a growing body of evidence suggesting an association between normal-tension glaucoma and dementia.”
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Materials provided by BMJ. Note: Content may be edited for style and length.

Physical activity is important in preventing heart and blood vessel disease in young people so long as they don’t undertake very strenuous activity on days when air pollution levels are high, according to a nationwide study of nearly 1.5 million people published today (Tuesday) in the European Heart Journal.
Until now, little has been known about the trade-offs between the health benefits of physical activity taking place outdoors and the potentially harmful effects of air pollution. Previous research by the authors of the current study had investigated the question in middle-aged people at a single point in time, but this is the first time that it has been investigated in people aged between 20-39 years over a period of several years. In addition, the researchers wanted to see what happens when people increase or decrease their physical activity over time.
The researchers from Seoul National University College of Medicine (South Korea), led by Professor Sang Min Park, looked at information from the National Health Insurance Service (NHIS) in South Korea for 1,469,972 young Koreans living in cities, who underwent two consecutive health examinations during two screening periods: 2009-2010 and 2011-2012. They followed up the participants from January 2013 to December 2018.
At each health check-up the participants completed a questionnaire asking about their physical activity in the past seven days and this information was converted into units of metabolic equivalent task (MET) minutes per week (MET-mins/week). The participants were divided into four groups: 0, 1-499, 500-999 and 1000 or more MET-mins/week. European Society of Cardiology guidelines recommend people should try to do 500-999 MET-mins/week and this can be achieved by, for example, running, cycling or hiking for 15-30 minutes five times a week, or brisk walking, doubles tennis or slow cycling for 30-60 minutes five times a week. [1]
The researchers used data from the National Ambient Air Monitoring System in South Korea to calculate annual average levels of air pollution, in particular the levels of small particulate matter that are less than or equal to 10 or 2.5 microns in diameter, known as PM10 and PM2.5 [2]. The amount of exposure to air pollution was categorised at two levels: low to moderate (less than 49.92 and 26.43 micrograms per cubic metre, μm/m3, for PM10 and PM2.5 respectively), and high (49.92 and 26.46 μm/m3 or more, respectively). [2]
Dr Seong Rae Kim, first author of the paper, said: “We found that in young adults aged 20-39 years old, the risk of cardiovascular diseases, such as stroke and heart attack, increased as the amount of physical activity decreased between the two screening periods in the group with low levels of exposure to air pollution.

Reece caught coronavirus during the first wave of the pandemic in March 2020, but like many twenty-somethings, he wasn’t hospitalised overnight.What he thought would be a mild illness became a protracted nightmare with his partner Alice becoming his carer. Months after his initial infection, he was diagnosed with CFS/ME (Chronic Fatigue Syndrome/Myalgic Encephalomyelitis) by his GP and referred to a specialist. His CFS/ME consultant later confirmed his CFS/ME symptoms were a form of ‘long Covid’ and referred him to a long Covid clinic.Video Journalist: Lorna Acquah

The administration is stepping up the pace of vaccinations and expanding access to shots, but it remains in a race against a virus on the upswing.WASHINGTON — President Biden, facing a rise in coronavirus cases around the country, called on Monday for governors and mayors to reinstate mask mandates as the director of the Centers for Disease Control and Prevention warned of “impending doom” from a potential fourth surge of the pandemic.The president’s comments came only hours after the C.D.C. director, Dr. Rochelle Walensky, appeared to fight back tears as she pleaded with Americans to “hold on a little while longer” and continue following public health advice, like wearing masks and social distancing, to curb the virus’ spread.The back-to-back appeals reflected a growing sense of urgency among top White House officials and government scientists that the chance to conquer the pandemic, now in its second year, may slip through its grasp. Coronavirus infections and hospitalizations are on the upswing, including a troubling rise in the Northeast, even as the pace of vaccinations is accelerating.“Please, this is not politics — reinstate the mandate,” Mr. Biden said, adding, “The failure to take this virus seriously is precisely what got us into this mess in the first place.”According to a New York Times database, the seven-day average of new virus cases as of Sunday was about 63,000, a level comparable with late October’s average. That was up from 54,000 a day two weeks earlier, an increase of more than 16 percent. Similar upticks in Europe have led to major surges in the spread of Covid-19, Dr. Walensky said.Public health experts say that the nation is in a race between the vaccination campaign and new, worrisome coronavirus variants. Although more than one in three American adults have received at least one shot and nearly one-fifth are fully vaccinated, the nation is a long way away from reaching so-called herd immunity — the tipping point that comes when spread of a virus begins to slow because so many people, estimated at 70 to 90 percent of the population, are immune to it.But states are rapidly expanding access to more plentiful quantities of the vaccine. On Monday, at least six — Texas, Kansas, Louisiana, North Dakota, Ohio and Oklahoma — made all adults eligible for vaccination. New York said that all adults would be eligible starting April 6.Mr. Biden said on Monday that the administration was taking steps to expand vaccine eligibility and access, including opening a dozen new mass vaccination centers. He directed his coronavirus response team to ensure that 90 percent of Americans would be no farther than five miles from a vaccination site by April 19.The president said doses were plentiful enough now that nine of 10 adults in the nation — or more — would be eligible for a shot by that date. Previously, he had called on states to broaden eligibility to all adults by May 1. He revised that promise because states, buoyed by projected increases in shipments, are opening their vaccination programs more rapidly than expected, a White House official said.But it was Dr. Walensky’s raw display of emotion that seemed to capture the angst of the moment. Barely three months into her new job, the former Harvard Medical School professor and infectious disease specialist acknowledged she was departing from her prepared script during the White House’s regular coronavirus briefing for reporters.She described “a feeling of nausea” she experienced last year when, caring for patients at Massachusetts General Hospital, she saw the corpses of Covid-19 victims piled up, overflowing from the morgue. She recalled how she stood — “gowned, gloved, masked, shielded” — as the last one in a patient’s room before they died alone, without family.Dr. Rochelle Walensky, the director of the C.D.C., said on Monday that the nation had “so much reason for hope,” but she warned of the potential for another virus surge.Anna Moneymaker for The New York Times“I am asking you to just hold on a little longer, to get vaccinated when you can, so that all of those people that we all love will still be here when this pandemic ends,” Dr. Walensky said. The nation has “so much reason for hope,” she added.“But right now,” she said, “I’m scared.”In nine states over the past two weeks, virus cases have risen more than 40 percent, The Times database shows. Michigan led the way with a 133 percent increase, and the Northeast has also seen a marked rise in virus cases. Connecticut reported a 62 percent jump over the past two weeks, and New York and Pennsylvania both reported increases of more than 40 percent.Michigan’s increase has not been traced to any one event, but epidemiologists have noted that cases started to rise after the state eased restrictions for indoor dining on Feb. 1 and lifted other restrictions in January. Other hot spots included North Dakota, where cases rose by nearly 60 percent, and Minnesota, where cases have risen 47 percent. Of those states, North Dakota is the only one currently without a mask mandate.The wave of new cases does come at the same time as some promising news: A C.D.C. report released Monday confirmed the findings of last year’s clinical trials that vaccines developed by Moderna and Pfizer were highly effective against Covid-19. The report documented that the vaccines work to prevent both symptomatic and asymptomatic infections “in real-world conditions.”Researchers followed nearly 4,000 health care employees and essential workers beginning in December. They found 161 infections among the unvaccinated workers, but only three among those who received two doses of vaccine. The study suggested even a single dose was 80 percent effective against infection two weeks after it was administered. Studies are continuing to determine whether vaccinated people can still transmit the virus to others, although many scientists consider that unlikely.A vaccination site on Monday in Houston. A recent drop in cases in Texas may be reversing. Go Nakamura for The New York TimesThe pace of vaccination continues to pick up. The seven-day average of vaccines administered hit 2.76 million on Monday, an increase over the pace the previous week, according to data reported by the C.D.C. On Sunday alone, nearly 3.3. million people were inoculated, said Andy Slavitt, a senior White House pandemic adviser.Broader eligibility pools should bolster that further, with more than three dozen states now allowing all adults to sign up for shots by mid-April.Minnesota will open up to all adults on Tuesday, and Connecticut on Thursday. Florida has lowered the age of eligibility to 40, and Indiana has lowered it to 30.At the same time, Covid surges in some states have health officials increasingly on edge. Similar escalations several weeks ago in Germany, France and Italy have now turned into major outbreaks, Dr. Walensky said.“We know that travel is up, and I just worry that we will see the surges that we saw over the summer and over the winter again,” she said.As his presidency enters its third month, Mr. Biden is still fighting some battles started by his predecessor, who turned the act of mask wearing into a political statement. As soon as he took office, Mr. Biden used his executive authority to impose mask requirements where he could — on federal property. And he urged all Americans to “mask up” for 100 days.But some governors, particularly in more conservative states, ignored him. When the governors of Mississippi and Texas announced this month that they would lift their mask mandates, Mr. Biden denounced the plans as a “big mistake” that reflected “Neanderthal thinking.”Texas’ governor this month allowed all businesses to open at full capacity and lifted the state’s mask mandate.Matthew Busch for The New York TimesIn Texas, a recent drop in cases may be reversing. Although The Times database shows that over the past two weeks coronavirus infections there have declined 17 percent, deaths have declined 34 percent and hospitalizations have declined 25 percent, the seven-day average of newly reported coronavirus infections was up on Sunday to 3,774. Last Wednesday, the average case count was at a low of 3,401.“There is something particularly difficult about this moment,” said Dr. Joshua M. Sharfstein, a former top Food and Drug Administration official who now teaches at the Johns Hopkins Bloomberg School of Public Health. With more and more Americans vaccinated and the potential to bring the pandemic to an end in sight, he said that “it feels like every case is unnecessary.”Dr. Walensky, who has issued several warnings in recent weeks about the need to keep up mask wearing and social distancing, said she planned to talk to governors on Tuesday about the risks of prematurely lifting restrictions.“I know you all so badly want to be done,” she said. “We are just almost there, but not quite yet.”Eileen Sullivan

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesThe Covid-19 vaccine blocks pretty much all cases of serious illness – but the government has been much more cautious about saying whether it stops people carrying the virus and infecting others. Until evidence had built up from lots of people being vaccinated, scientists could not say for sure if the jab would stop transmission – and there was concern those vaccinated might stop taking precautions, potentially leading to a rise in infections. But with some now refusing the vaccine in the belief it will not stop them passing on the virus, is this caution becoming counterproductive?A number of people have contacted the BBC, saying they believe the jab could stop them becoming severely ill only. But the evidence is moving fast.Protection from the vaccine may not be perfect and people still need to be careful – but this does not mean it provides no protection to others. It is becoming increasingly clear the jab is a very big step towards protecting those around you – particularly people who are vulnerable, including the elderly and those with care needs such as learning disabilities or mental illness. And a growing body of real-world evidence suggests it stops a big chunk of people catching the virus at all – they do not fall ill and cannot infect people. When will over-40s get a jab?Covid vaccines: How fast is worldwide progress?The vaccines that work – and the others on the wayThink of a ladder with the worst Covid effects, intensive-care admission or death, at the top and the mildest, no or asymptomatic infection, at the bottom.Being vaccinated effectively moves people down the rungs of this ladder.Even the small number who do not receive complete protection might move from a very high risk of dying down to mild or moderate symptoms. And those who would have very mild or asymptomatic Covid without the jab are probably most likely to move down to no infection at all.What does the government say?”There has been some early evidence that suggests vaccines do have an impact on transmission,” an official said.”But the full impact on infection rates will not become clear until a large number of people have been vaccinated.”It is important to continue following the national restrictions, instructions from NHS Test and Trace, and to self-isolate if you are instructed to do so, even if you have had the vaccine.”What about the evidence?Regular testing of participants in the Oxford-AstraZeneca vaccine trials, with or without symptoms, found positive tests fell by more than half.And this suggested “the potential for a substantial reduction in transmission”, the team reviewing the trial results said.The Pfizer-BioNTech trial participants, meanwhile, were tested only if they had symptoms.But a later study of 40,000 health workers in England suggested one Pfizer-BioNTech dose cut the risk of infection – symptomatic or otherwise – by 70%, and two doses by 85%.Also, people living with vaccinated NHS staff in Scotland were considerably less likely to catch the virus than those living with unvaccinated health workers. And a separate analysis of the test results of hospital workers in Cambridge found a 75% decrease in asymptomatic infections after vaccination. In Israel, the Pfizer-BioNTech vaccine appeared to reduce all infections by as much as 90%, although the Ministry of Health could not be certain of the precise number as not everyone came forward for asymptomatic testing. And, a separate Israeli study found, the infections there had much lower “viral loads” – people shed less virus, meaning they would be less contagious as well as at lower risk of becoming ill.Similar conclusions have been drawn in studies of patients in the US and care-home residents in England.And, overall, the picture is clear – vaccines reduce transmission.Aren’t asymptomatic cases less contagious anyway?Asymptomatic Covid cases do seem to be less contagious – but those without symptoms may unknowingly infect more people. Studies estimate between a third and a half of new cases were caught this way.And those vaccinated are much less likely to pass on the virus.You only need to look at the disproportionately large number of outbreaks and deaths in care homes during the first wave of the pandemic to see the impact of relying on symptoms. And people are most infectious – at very high risk of passing on the virus – the day or two before symptoms develop.Follow Rachel on Twitter

One specific protein may be a master regulator for changing how cancer cells consume nutrients from their environments, preventing cell death and increasing the likelihood the cancer could spread, a study from the University of Notre Dame has shown.
The study, published in Cell Reports, was completed in the laboratory of Zachary Schafer, the Coleman Foundation Associate Professor of Cancer Biology in the Department of Biological Sciences.
Schafer and collaborators found a protein called SGK1, known to be activated in a variety of cancer cell types, signals the cell to take up nutrients. These nutrients include glucose, which allows the cell to survive after it detaches from the scaffold of proteins it had been attached to, called the extracellular matrix. Non-cancerous cells often die after detaching from the extracellular matrix, but SGK1 activity promotes survival and therefore increases the chances that the cancer could spread, or metastasize.
“If you better understand precisely how cancer cells that are potentially metastatic survive in these sorts of foreign environments, then you can potentially antagonize those survival pathways and selectively cause those cells to die,” said Schafer, also an affiliate member of Notre Dame’s Harper Cancer Research Institute.
More than 90 percent of cancer deaths are caused by metastasis of cancer cells from one location to another, Schafer said. For instance, breast cancer can metastasize to the brain, and metastatic cancer cells need to adapt to the new environment there.
There are unique circumstances where the SGK1 protein is critically important, so there might be a vulnerability that researchers can target and alter the way the cells process their nutrients, said Schafer.
This discovery appears to be broadly relevant across many different types of cancer, Schafer said, with research in this paper focused on breast and colon cancer cells grown in cultures under different conditions. The research took place over a number of years, and in addition to a collaboration with the Duke University School of Medicine and Northwestern University Feinberg School of Medicine, several Notre Dame postdoctoral, graduate and undergraduate researchers assisted with the work.
The next step in the research is to complete a “proof of principle” study, which is an early-stage investigation of how this knowledge could be leveraged for clinical benefit. Such a study could reveal if different agents — which could become therapeutics — could potentially eliminate the cells in question.
“If you can kill those cells that are potentially metastatic, then potentially you can get to a point where you can block cancer dissemination,” Schafer said.
The study was funded by the American Cancer Society, the Phi Beta Psi National Project, the Coleman Foundation, the National Science Foundation (through a Research Experience for Undergraduate grant) and the Malanga Family Excellence Fund for Cancer Research.
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Materials provided by University of Notre Dame. Original written by Deanna Csomo McCool. Note: Content may be edited for style and length.

Since the beginning of the pandemic, a loss of smell has emerged as one of the telltale signs of COVID-19. Though most people regain their sense of smell within a matter of weeks, others can find that familiar odors become distorted. Coffee smells like gasoline; roses smell like cigarettes; fresh bread smells like rancid meat.
This odd phenomenon is not just disconcerting. It also represents the disruption of the ancient olfactory circuitry that has helped to ensure the survival of our species and others by signaling when a reward (caffeine!) or a punishment (food poisoning!) is imminent.
Scientists have long known that animals possess an inborn ability to recognize certain odors to avoid predators, seek food, and find mates. Now, in two related studies, researchers from the Yu Lab at the Stowers Institute for Medical Research show how that ability, known as innate valence, is encoded. The findings, published in the journals Current Biology and eLife, indicate that our sense of smell is more complicated — and malleable — than previously thought.
Our current understanding of how the senses are encoded falls into two contradictory views — the labeled-line theory and the pattern theory. The labeled-line theory suggests that sensory signals are communicated along a fixed, direct line connecting an input to a behavior. The pattern theory maintains that these signals are distributed across different pathways and different neurons.
Some research has provided support for the labeled-line theory in simple species like insects. But evidence for or against that model has been lacking in mammalian systems, says Ron Yu, PhD, an Investigator at the Stowers Institute and corresponding author of the reports. According to Yu, if the labeled-line model is true, then the information from one odor should be insulated from the influence of other odors. Therefore, his team mixed various odors and tested their impact on the predicted innate responses of mice.
“It’s a simple experiment,” says Qiang Qiu, PhD, a research specialist in the Yu Lab and first author of the studies. Qiu mixed up various combinations of odors that were innately attractive (such as the smell of peanut butter or the urine of another mouse) or aversive (such as the smell of rotting food or the urine of a predator). He then presented those odor mixtures to the mice, using a device the lab specially designed for the purpose. The device has a nose cone that can register how often mice investigate an odor. If mice find a particular mixture attractive, they poke their nose into the cone repeatedly. If they find the mixture aversive, they avoid the nose cone at all costs.

Far more work is needed to understand how the pandemic began, the report says, but it is not clear that Beijing will cooperate. “We may never find the true origins,” an expert said.For 27 days, they searched for clues in Wuhan, visiting hospitals, live animal markets and government laboratories, conducting interviews and pressing Chinese officials for data, but an international team of experts departed the country still far from understanding the origins of the coronavirus pandemic that has killed nearly 2.8 million people worldwide.The 124-page report of a joint inquiry by the World Health Organization and China — to be released officially on Tuesday but leaked to the media on Monday — contains a glut of new detail but no profound new insights. And it does little to allay Western concerns about the role of the Chinese Communist Party, which is notoriously resistant to outside scrutiny and has at times sought to hinder any investigation by the W.H.O. The report is also not clear on whether China will permit outside experts to keep digging.“The investigation runs the risk of going nowhere, and we may never find the true origins of the virus,” said Yanzhong Huang, senior fellow for global health at the Council on Foreign Relations.The report, an advance copy of which was obtained by The New York Times, says that China still does not have the data or research to indicate how or when the virus began spreading. Some skeptics outside the country say that China may have more information than it admits.The expert team also dismisses as “extremely unlikely” the possibility that the virus emerged accidentally from a Chinese laboratory, even though some scientists say that is an important question to explore.The Chinese government, while granting some degree of access and cooperation, has repeatedly tried to bend the investigation to its advantage. The report was written jointly by a team of 17 scientists from around the world, chosen by the W.H.O., and 17 Chinese scientists, many of whom hold official positions or work at government-run institutions, giving Beijing great influence over its conclusions.Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle, said he was not convinced that a laboratory leak was extremely unlikely, after seeing a copy of the report. He said he agreed that it was highly plausible that the virus could have evolved naturally to spread to humans, but he did not see any reasoning in the report to dismiss the possibility of a lab escape.One member of the team of experts, Peter Daszak, a British disease ecologist who runs EcoHealth Alliance, a New York-based pandemic prevention group, pushed back against the criticism of the team’s work and of China’s level of cooperation. He said the lab leak hypothesis was “political from the start.” Dr. Daszak added that the W.H.O. team was not restricted in its interviews with scientists who were on the ground at the start of the pandemic.He himself has been accused of having a conflict of interest because of his past research on coronaviruses with the Wuhan Institute of Virology, which, he said, was what a disease ecologist should be doing.“We were in the right place because we knew that there was a risk of the virus emerging,” said Dr. Daszak. “We were working there with this exact viral group and it happened.”The prevailing theory remains that the virus originated in bats, jumped to another animal, and then mutated in a way that enabled it to transmit to humans, and from human to human. But the process of tracing the origins of a virus is notoriously painstaking.To answer numerous remaining questions, the report recommends further retrospective studies of human infections, including the earliest cases, and more virus testing of livestock and wildlife in China and Southeast Asia. It also calls for more detailed tracing of pathways from farms to markets in Wuhan that would require extensive interviews and blood tests for farmers, vendors and other workers.But it is unclear to what degree China will cooperate, and the country’s secretive and defensive behavior has helped fuel theories that it was somehow to blame for the start of the pandemic. Local officials in Wuhan at first tried to conceal the outbreak; Beijing has since expelled many Western journalists and has floated evidence-free theories about the virus originating elsewhere — though the earliest known cases were all in China, and experts agree it almost certainly first appeared there.“We’ve got real concerns about the methodology and the process that went into that report, including the fact that the government in Beijing apparently helped to write it,” Secretary of State Antony J. Blinken said a CNN interview broadcast on Sunday.China’s increasingly acrimonious relationship with the United States and other countries has also complicated the inquiry. The Biden administration has repeatedly criticized China’s lack of transparency, including its refusal to hand over raw data about early Covid-19 cases to investigators when they visited Wuhan. Chinese officials have bristled, suggesting that the United States should welcome the W.H.O. to examine the unfounded theory that the virus might have originated in a U.S. Army laboratory.“We will never accept the groundless accusations and wanton denigration by the United States on the issue of the epidemic,” Zhao Lijian, a spokesman for the Chinese foreign ministry, said at a regular news briefing in Beijing on Monday.In bombastic news articles, Chinese propagandists have hailed the inquiry as a sign of China’s openness to the world and a vindication of the government’s handling of the epidemic.The W.H.O. has come under pressure to demand more data and research from the Chinese government. But by design, the global health agency is beholden to its member countries, which did not grant the W.H.O. team sweeping powers to carry out, for example, forensic investigations of laboratory mishaps in China.While much of the report was heavy on detail about molecular studies, virus evolution and possible animal hosts, the section dealing with the possibility of a lab leak was cursory at best. While the virus’s animal origin is largely undisputed, some scientists maintain that the virus could have been collected and present in the lab of the Wuhan Institute of Virology, even though Chinese scientists say it was not.China’s lack of transparency as well as other concerns prompted a small group of scientists not affiliated with the W.H.O. to call this month for a new inquiry into the origin of the pandemic. They said such an inquiry should consider the possibility that the virus escaped from a laboratory in Wuhan or infected someone inside it.The lab leak theory has been promoted by some officials in the Trump administration, including Dr. Robert Redfield, the former director of the Centers for Disease Control and Prevention, in comments to CNN last week. He offered no evidence and emphasized that it was his opinion; the theory has been widely dismissed by scientists and U.S. intelligence officials.Matt Apuzzo and Apoorva Mandavilli contributed reporting. Albee Zhang contributed research.

A team led by investigators at Weill Cornell Medicine and NewYork-Presbyterian has used advanced technology and analytics to map, at single-cell resolution, the cellular landscape of diseased lung tissue in severe COVID-19 and other infectious lung diseases.
In the study, published online March 29 in Nature, the researchers imaged autopsied lung tissue in a way that simultaneously highlighted dozens of molecular markers on cells. Analyzing these data using novel analytical tools revealed new insights into the causes of damage in these lung illnesses and a rich data resource for further research.
“COVID-19 is a complex disease, and we still don’t understand exactly what it does to a lot of organs, but with this study we were able to develop a much clearer understanding of its effects on the lungs,” said co-senior author Dr. Olivier Elemento, professor of physiology and biophysics, director of the Caryl and Israel Englander Institute for Precision Medicine, associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine at Weill Cornell Medicine and co-Director of the WorldQuant Initiative for Quantitative Prediction, which funded the technology for single cell analysis of tissue. “I think the technological approach we used here is going to become standard for studying such diseases.”
Traditional tissue analysis, often using chemical stains or tagged antibodies that label different molecules on cells and can reveal important features of autopsied tissues. However, this approach is limited in the number of features it can mark simultaneously. It also usually doesn’t allow detailed analyses of individual cells in tissues while retaining information about where the cells were in the tissue.
The main technology the investigators employed in the study, a technology called imaging mass cytometry, largely overcomes those limitations. It uses a collection of metal-tagged antibodies that can simultaneously label up to several dozen molecular markers on cells within tissues. A special laser scans the labeled tissue sections, vaporizing the metal tags, and the metals’ distinct signatures are detected and correlated with the laser position. The technique essentially maps precisely where cells are in the sample as well as each cell’s surface receptors and other important identifying markers. Altogether over 650,000 cells were analyzed.
The researchers applied the method to 19 lung tissue samples autopsied from patients who had died of severe COVID-19, acute bacterial pneumonia, or bacterial or influenza-related acute respiratory distress syndrome, plus four lung tissue samples autopsied from people who had had no lung disease.

Chimeric antigen receptor T-cell therapy, or CAR T, is a relatively new type of therapy approved to treat several types of aggressive B cell leukemias and lymphomas. Many patients have strong responses to CAR T; however, some have only a short response and develop disease progression quickly. Unfortunately, it is not completely understood why these patients have progression. In an article published in Proceedings of the Royal Society B, Moffitt Cancer Center researchers use mathematical modeling to help explain why CAR T cells work in some patients and not in others.
CAR T is a type of personalized immunotherapy that uses a patient’s own T cells to target cancer cells. T cells are harvested from a patient and genetically modified in a laboratory to add a specific receptor that targets cancer cells. The patient then undergoes lymphodepletion with chemotherapy to lower some of their existing normal immune cells to help with expansion of the CAR T cells that are infused back into the patient, where they can get to work and attack the tumor.
Mathematical modeling has been used to help predict how CAR T cells will behave after being infused back into patients; however, no studies have yet considered how interactions between the normal T cells and CAR T cells impact the dynamics of the therapy, in particular how the nonlinear T cell kinetics factor into the chances of therapy success. Moffitt researchers integrated clinical data with mathematical and statistical modeling to address these unknown factors.
The researchers demonstrate that CAR T cells are effective because they rapidly expand after being infused back into the patient; however, the modified T cells are shown to compete with existing normal T cells, which can limit their ability to expand.
“Treatment success critically depends on the ability of the CAR T cells to multiply in the patient, and this is directly dependent upon the effectiveness of lymphodepletion that reduces the normal T cells before CAR T infusion,” said Frederick Locke, M.D., co-lead study author and vice chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt.
In their model, the researchers discovered that tumor eradication is a random, yet potentially highly probable event. Despite this randomness of cure, the authors demonstrated that differences in the timing and probability of cures are determined largely by variability among patient and disease factors. The model confirmed that cures tend to happen early, within 20 to 80 days before CAR T cells decline in number, while disease progression tends to happen over a wider time range between 200 to 500 days after treatment.
The researchers’ model could also be used to test new treatments or propose refined clinical trial designs. For example, the researchers used their model to demonstrate that another round of CAR T-cell therapy would require a second chemotherapy lymphodepletion to improve patient outcomes.
“Our model confirms the hypothesis that sufficient lymphodepletion is an important factor in determining durable response. Improving the adaptation of CAR T cells to expand more and survive longer in vivo could result in increased likelihood and duration of response,” explained Philipp Altrock, Ph.D., lead study author and assistant member of the Integrated Mathematical Oncology Department at Moffitt.
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Materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Content may be edited for style and length.