Publisher Health

The death rate linked to extreme temperatures will increase significantly under global warming of 2°C, finds a report by researchers from UCL and the University of Reading.
Temperature-related mortality — where a death is directly linked to climate temperature — in England and Wales during the hottest days of the year will increase by 42% under a warming scenario of 2°C from pre-industrial levels. This means an increase from present-day levels of around 117 deaths per day, averaged over the 10 hottest days of the year, to around 166 deaths per day. The findings underline the importance of keeping global warming levels to below 2°C.
At current global warming levels of around 1.21°C we see a slight decrease in temperature-related mortality in winter and a minimal net effect in summer, meaning that overall, at this level of warming we see a slight decrease in temperature-related mortality rate.
In the paper, published in Environmental Research Letters, the team examined the impact of climate change on temperature-related mortality rates in England and Wales, focusing on the risk from heat in summer and cold in winter. They found that as the global mean temperature increases, temperature-related mortality in summer will increase at a much faster, non-linear rate.
The rate of increase particularly speeds up at 2°C of warming, with a much higher risk appearing beyond 2.5°C. The researchers say that 3°C warming could lead to a 75% increase in mortality risk during heatwaves.
When plotted on a graph, the relationship between temperature and mortality is roughly u-shaped, meaning that at extremely high temperatures, which the population is not used to, the mortality risk increases sharply for each degree rise of daily mean temperature.

A surface that feels smooth to human touch could be pretty rough to a protein. That can be good or bad, depending on what you want that protein to do.
Exactly how proteins interact with solid surfaces is a concern for health care manufacturers who design drugs, make biosensors or develop anti-fouling materials.
The mechanisms that control these interactions are hard to see, but researchers at Rice University are changing that with a microscopy technique to assess the effects of surface roughness as well as water-repelling properties (hydrophobicity) and electrostatic charge. The ability to tune those parameters will lead to more predictable materials.
“The main idea is to understand the how the combination of these properties influences protein dynamics,” said Anastasiia Misiura, lead author of a study in the Journal of Chemical Physics and a graduate student in the Rice lab of chemist Christy Landes. “It turned out that roughness and hydrophobicity are opposite forces, but proteins get stuck on areas that are very rough.”
The paper, an “editor’s choice,” is part of the journal’s “Ever-Expanding Optics of Single Molecules and Nanoparticles” collection.
How molecules interact at surfaces is important at every scale in the physical realm, from grinding planetary plates to brakes grabbing the wheels in your car to the invisible molecular transactions that make life possible. Understanding these mechanisms at the very smallest level is the focus of Landes’ lab as its members attempt to clarify what’s actually happening down there.

For Dr. Ayoade Alakija, saying no was not an option when she was asked to lead efforts to expand Covid-19 testing and treatments to underserved regions.This interview is part of our latest Women and Leadership special report, which highlights women making significant contributions to the major stories unfolding in the world today. The conversation has been edited and condensed.Dr. Ayoade Alakija, an infectious disease specialist based in Nigeria, is co-chair of the African Union’s Vaccine Delivery Alliance (AVDA). In December 2021, Dr. Alakija, nicknamed Yodi, was put in charge of accelerating equitable access to Covid-19 tests, treatments and vaccines for the World Health Organization’s global initiative known as the Access to Covid-19 Tools Accelerator. She uses the term “global north” to describe high-income countries and “global south” to describe low- and middle-income countries.Throughout the pandemic you have been critical about vaccine inequity, especially in Africa. How did it feel when the W.H.O. director-general Dr. Tedros Adhanom Ghebreyesus asked you to be special envoy to the Access to Covid-19 Tools (ACT) Accelerator?I had been one of the most critical voices at some of the outputs of the ACT Accelerator. I had been agitator No. 1 for vaccine inequity. So my first thought was, “Oh my God, they will all hate me.”It was a shake-up of the status quo; a fox in the henhouse. When Tedros called me to ask if I would do it, I said, “Have you got the right number?” And then I said, “Oh, no, no, no.” So he asked me to think about it, saying, “Your voice is needed, your steer is needed.”I spoke to my husband, and he said, “Yodi, you have been at the forefront of saying those of us from the global south need to be heard. They have invited you to that table, you cannot say no.”Dr. Ayoade Alakija on her approach to getting more women in positions of power: “So if they don’t give you a seat at the table, pull up a chair,” she said. “And if they don’t make space, then get on the table.”Alaye MWhat does your role entail?I operate 16 to 18 hours a day, advising governments, health ministers, finance ministers and the ACT Accelerator leads, coordinating with AVDA colleagues on vaccine shipments, deliveries and bottlenecks. There are also speaking and media engagements I undertake in order to advocate on the issue of vaccine equity, and equitable access to health care tools.How do we achieve vaccine equity?When we ascribe the same value to lives in the global south as we do to lives in the global north. We can only achieve it when we don’t think it’s OK for people to be dying in Mombasa or in Kibera of diseases that no longer exist in London or New York. When we value each other the same. Because at the moment there are those who are saying, “Oh, well, it’s not so bad in Africa. So maybe we don’t really need to vaccinate them. We’re not seeing the I.C.U.s being completely overrun.” Well, that’s because there are no I.C.U.s. That’s because there are no health centers. That’s because people are dying silently.You began your clinical career working with H.I.V. and AIDS patients, then decided to pursue your master’s degree in public health in your early 20s. Did you face any obstacles early in your career?When I applied to the London School of Hygiene and Tropical Medicine to study public health, I received a rejection letter saying, “This course tends to be for really senior level public servants, ministers or permanent secretaries from different countries around the world. You are very young so we are not accepting you on to this course.”I was outraged. My husband and I were living in London at the time, so I marched into the school and demanded to see the dean, who at the time was Richard Feachem. I threw the letter on the desk and I said, “What is the meaning of this? This is what I want to do and I am not leaving until I am doing what I applied to do.” He sat back in his chair and said, “I really look forward to the day you are running the world.” He then directed me to someone in admissions.You’ve been vocal about the need for more women in positions of power when it comes to the world’s Covid-19 response. How do we achieve that?It has slapped me in the face so much during this pandemic, the fact that the global health leaders are men. A lot of women tend to be No. 2s, so they don’t quite have the decision-making power, the voice.I was at a conference in Rwanda, and there was a group of men who had invited themselves into this mentoring session that I was doing for young women. And they were standing right in front of the only table in the room. So I tapped each on the shoulder and said, “Excuse me.” And they sort of looked at me and said dismissively, “Oh, yeah, hi.”So I parted through them and I climbed on a chair, and then on a table. The conference erupted. I got the mic and I said, “Right here, this is what we’re talking about. That even if you pull up a chair and you sort of get into the conversation politely, they look at you like, ‘eh?’”So if they don’t give you a seat at the table, pull up a chair. And if they don’t make space, then get on the table.Do you believe that Covid has disproportionately affected the lives of women and girls, especially in Africa?There is another silent pandemic going on here with child marriage — people selling off their daughters because of the economic impact of Covid. People can’t afford to feed their families, therefore, it is the girls who have to go.Even for vaccines, the prioritization in communities means that if there are a few vaccines available in the country, and people are willing to go and get it, the man will go and get it. But the woman won’t.How do we get more vaccines in arms?It is not as simple as hesitancy. Hesitancy is a function of trust — trust in systems, trust in governments. There needs to be a more regular, more consistent, predictable supply of vaccines. We have to also look at the wider strengthening of the health systems. It has to be a component of our delivery of vaccines and our preparation for the next outbreak or the next pandemic or just preparation for life, really.

A funding dispute with Republican senators may complicate the Biden administration’s efforts to guarantee supplies of free antiviral pills and monoclonal antibody treatments this year to Americans who test positive for the coronavirus.At issue is whether the White House has provided the level of detail desired by Republicans about the trillions of dollars in Covid relief spending that Congress previously authorized. A group of three dozen Republican senators, led by Mitt Romney of Utah, told the White House last week that they would not consider billions in new Covid relief spending without a more detailed accounting of how existing funds had been spent and whether any money was left over.“It is not yet clear why additional funding is needed,” they wrote in a letter to President Biden on Wednesday.Administration officials have requested $22.5 billion for additional vaccines, oral antivirals and monoclonal antibodies, testing and support for the global vaccination effort.Republican senators have suggested that the administration should divert money from the $1.9 trillion pandemic law to the areas of need, rather than have Congress spend billions of new funds.Jen Psaki, the White House press secretary, said on Friday that the current supply of monoclonal antibodies will run out by May and stocks of oral antivirals would be depleted by September without new purchases. “This is an urgent request,” she said.A breakdown of spending on Covid-related supplies like testing, vaccines and treatments provided to Congress by the Biden administration and obtained by The New York Times indicated that nearly all existing funds had been spent or committed in signed contracts, and that any remaining funds had been allocated. The administration offered some detail on its plans for new Covid spending in a letter to Congress on Wednesday.The funding dispute is playing out as the White House tries to put in place plans that it says are essential to the country’s efforts to return to a semblance of normalcy.Hundreds of pharmacies and other health facilities were prepared to launch a “test to treat” program this week allowing people to walk in for a coronavirus test and, if the results are positive, to leave with free antiviral pills, administration officials said.Last week, the Department of Defense told STAT, a medical news outlet, that it would exercise contract options to buy more of Pfizer’s antiviral treatment, known as Paxlovid, once funding became available.The White House also said that Americans who had already received a package of four free at-home coronavirus tests from the government would become eligible this week to place a second order on covidtests.gov.New virus cases in the United States have plunged in recent weeks, but more than 1,500 Americans are still dying from the virus each day on average.There are also signs that a particular version of the Omicron variant that is even more contagious than the one that tore through the United States this winter is becoming more prevalent, rising to roughly 8 percent of sequenced cases in the United States by late February. But overall cases remain on the decline and vaccines look to be equally effective against the Omicron subvariant, which does not appear to be any more severe.Biden administration officials hope to include the $22.5 billion in coronavirus aid, alongside humanitarian and military aid for Ukraine, in a sprawling catchall spending package that would fund the government for the remainder of the fiscal year. Congress has until March 11, when funding is set to lapse, to hammer out the details of a deal.

The treatment could be lifesaving for many who cannot get protection from the vaccine, but confusion about the drug has made some doctors slow to prescribe it.Sasha Mallett, Sue Taylor and Kimberly Cooley all have immune deficiencies that make them especially vulnerable to Covid-19, and all have tried to get the same thing: a new treatment that can prevent the disease in people who either cannot produce antibodies after receiving a coronavirus vaccine or cannot get vaccinated at all.Ms. Cooley, a liver transplant recipient in Duck Hill, Miss., got the antibody drug, called Evusheld, from her transplant team at the University of Mississippi Medical Center with no trouble. But Ms. Taylor, of Cincinnati, was denied the treatment by two hospitals near her home. And Dr. Mallett, a physician in Portland, Ore., had to drive five hours to a hospital willing to give her a dose.As much of the nation unmasks amid plummeting caseloads and fresh hope that the pandemic is fading, the Biden administration has insisted it will continue protecting the more than seven million Americans with weakened immune systems who remain vulnerable to Covid. Evusheld, which was developed by AstraZeneca with financial support from the federal government, is essential to its strategy.But there is so much confusion about the drug among health care providers that roughly 80 percent of the available doses are sitting unused in warehouses and on pharmacy and hospital shelves — even as patients like Ms. Taylor, 67, and Dr. Mallett, 38, go to great lengths, often without success, to get them.Because they have a weakened response to the coronavirus vaccine and may not be able to fight off Covid-19, many immunocompromised people have continued to isolate themselves at home and feel left behind as the country reopens. Evusheld, which is administered in two consecutive injections, appears to offer long-lasting protection — perhaps for half a year — giving it considerable appeal for this group.For now, though, the drug is in short supply. Because it is authorized only for emergency use, it is being distributed by the federal government. The Biden administration has purchased 1.7 million doses — enough to fully treat 850,000 people — and had nearly 650,000 doses ready for distribution to the states as of this past week, according to a senior federal health official. But only about 370,000 doses have been ordered by the states, and fewer than a quarter of those have been used.“There’s so many other people who are scrapping and driving for hours to get Evusheld,” Ms. Cooley, 40, said, “when in Mississippi it’s sitting on the shelves.”Interviews with doctors, patients and government officials suggest the reasons the drug is going unused are varied. Some patients and doctors do not know Evusheld exists. Some do not know where to get it. Government guidelines on who should be prioritized for the drug are scant. In some hospitals and medical centers, supplies are being reserved for patients at the highest risk, such as recent transplant recipients and cancer patients, while doses in other areas of the country are being given out through a lottery or on a first-come, first-served basis.Hesitance is also an issue. Some doctors and other providers do not know how to use Evusheld and are thus loath to prescribe it. The fact that it is an antibody treatment can be confusing, because most such treatments are used after someone gets Covid rather than for preventive care.Adding to the confusion are revised Food and Drug Administration guidelines for Evusheld, released last month, that called for doubling the initial recommended dose after data showed the drug may be less effective against certain variants.Evusheld is a key piece of the Biden administration’s strategy to protect the more than seven million Americans with weakened immune systems.Ted S. Warren/Associated Press“It is overwhelming and it’s all new,” said Dr. Mitchell H. Grayson, chief of the allergy and immunology division at Nationwide Children’s Hospital in Columbus, Ohio. “Providers are definitely trying to keep up, it’s just — I don’t know how well everyone’s doing with that.”Roughly 3 percent of Americans are characterized by health professionals as immunocompromised because they have a disease that weakens their body’s immune response or are receiving a treatment that does so. They include transplant recipients and people with conditions like cancer, lupus and rheumatoid arthritis.Evusheld’s arrival in December immediately set off a scramble. In Facebook groups and online messages, patients and their loved ones began swapping information about how to get it. Government data sets about Evusheld’s availability were so complex and confusing that a software developer in the Seattle area, Rob Relyea, developed his own mapping tool that tracks how much of the drug is available and which providers have it.“People should know where to go to get in line,” he said.Mr. Relyea, 51, had a vested interest: His wife, Rebecca, is in remission from cancer. They tried 10 hospitals unsuccessfully but then got the drug through luck, as Ms. Relyea’s name was picked in a lottery for Evusheld at a hospital near their home in early February, he said.But they have not heard anything yet about scheduling a second dose, which Ms. Relyea needs based on the new recommendations.Dr. Mallett, in Oregon, was one of many who were desperate to get the drug. She has common variable immunodeficiency, a condition that keeps her immune system from making enough antibodies. Her son started attending kindergarten in person last fall, and when the Omicron variant surged, his teacher and classmates began testing positive for Covid.To find Evusheld, Dr. Mallett scoured an online government database of shipments and spent weeks cold-calling hospitals, pharmacies and health organizations that received the drug.When she finally found a hospital in La Grande, Ore., willing to give her a dose, she worked with her physician to enroll as a patient there. Then she dropped everything and drove to the hospital in the rain, received the shots and immediately turned back — an 11-hour trip in total.Sasha Mallett was eager to find a dose of Evusheld, but many of the health workers she called had not even heard of it.Amanda Lucier for The New York TimesDr. Mallett is highly educated, medically savvy, wealthy and easily able to take time away from her job — privileges that helped her get a dose, but that many others do not have.“I definitely have a lot of lingering ethical qualms about how I went about getting this medication,” she said. “Did I take advantage of our broken system?”Many of the health workers Dr. Mallett called while she was trying to find a dose had not even heard of Evusheld — even if their workplaces had the drug in stock.Some experts argue that Evusheld should go first to people who cannot get vaccinated because of severe allergies and to those who produce the fewest antibodies in response to coronavirus vaccines. But antibodies are only one component of the immune system, and the Centers for Disease Control and Prevention still recommends against using tests that determine antibody levels to assess someone’s immunity.“The biggest problem is that there is absolutely no guidance or prioritization or any rollout in place at all, and it’s been a mess,” said Dr. Dorry Segev, a transplant surgeon at N.Y.U. Langone Health who has been studying coronavirus vaccines in transplant patients. “Without formal guidelines, you really can’t do anything.”The Coronavirus Pandemic: Key Things to KnowCard 1 of 3Mask guidance.

New data suggests overall abortions declined much less than previously known, because women traveled out of state or ordered pills online.The impact of the Texas abortion law was partly offset by trips to out-of-state clinics, and by abortion pillsEstimated number of monthly abortions among Texas residents

The parents of a five-year-old girl have said they believe she is the only child in the world to have a rare genetic condition.Isla was born with mandibuloacral dysplasia, which causes features of premature ageing.The family have said they do not know what her future holds and have used social media to raise awareness of her condition.Prof Pradeep Vasudevan, consultant clinical geneticist at Leicester’s Hospitals, said: “Isla’s condition is very rare – fewer than 50 cases have been recorded in medical literature. “Because of this, many cases most likely go misdiagnosed or undiagnosed making it difficult to determine the true frequency of mandibuloacral dysplasia in the general population.”Video journalist: Chris WaringFollow BBC East Midlands on Facebook, Twitter, or Instagram. Send your story ideas to eastmidsnews@bbc.co.uk.

Investigators from Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center have discovered how a drug for multiple sclerosis interacts with its targets, a finding that may pave the way for better treatments.
The study, published Feb. 8 in Nature Communications, details the precise molecular structure of the multiple sclerosis drug siponimod as it interacts with its target, the human S1P receptor 1 (S1P1), and off-target receptors using a cutting-edge electron microscopy technique called cryo-EM. This knowledge could help scientists develop drugs for the disease that are less likely to miss their targets.
“This discovery will help us improve drugs for multiple sclerosis and reduce their side effects,” said the study’s co-senior author Dr. Xin-Yun Huang, professor of physiology and biophysics at Weill Cornell Medicine.
In patients with multiple sclerosis, immune cells called lymphocytes attack and destroy the protective sheath around nerve cells, causing progressive neurologic symptoms. Scientists developed immune-suppressing drugs that block the release of these lymphocytes from the lymph nodes by binding to S1P1 receptors. But the first-generation version of these drugs could also bind to related receptors including S1P3, which caused unwanted side effects including an abnormal heart rhythm. To address this problem, scientists created next-generation medications like siponimod that bind more selectively to S1P1 and another receptor called S1P5. But this didn’t eliminate all unwanted side effects.
The new study, co-led by Dr. Shian Liu, a research associate at Weill Cornell Medicine, and Navid Paknejad, a graduate student at Memorial Sloan Kettering, reveals how siponimod binds to these two receptors and the features of the molecule that prevent it from binding to unwanted targets like S1P2, S1P3 and S1P4. Scientists can use this information to modify the drug to help it attach more tightly to its target (S1P1) and less likely to bind with unintended target (S1P5), reducing the risk of side effects.
“This new structural information will help us develop the next generation of multiple sclerosis drugs,” Dr. Huang said.
The study also helps explain how naturally occurring lipids can regulate the immune system, the nervous system and lung function. The team found that nearly identical lipids called sphingosine 1-phosphate and lysophosphatidic acid assumed very different shapes when bound to their target receptors.
“Lipids are highly plastic molecules, and the structures reveal how the receptors leverage subtle differences in the lipids structures to discriminate between them,” said co-senior author Dr. Richard Hite, a structural biologist at Memorial Sloan Kettering and an assistant professor in the biochemistry and structural biology and the physiology, biophysics and systems biology programs at the Weill Cornell Graduate School of Medical Sciences.
“This explains how lipids can play very different roles in the body even though their chemical structures are very similar,” Dr. Huang said.
The finding highlights the importance of carefully designing lipid-based drugs to prevent them from missing their targets. “We need to make lipid-based drugs that are very specific to reduce the risk of side effects,” he said.
These new insights may help scientists develop improved treatments for other autoimmune diseases like inflammatory bowel disease, psoriasis and systemic lupus. They might also help scientists create lipid-based therapies for conditions that affect the brain or lungs. For example, Dr. Huang noted that there are currently lipid-based drugs in clinical trials to reduce lung stiffening in patients with COVID-19.
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Take a cell-deep tour of a brain afflicted with Alzheimer’s disease, and you will find minuscule clumps of protein that seem suspicious. Ever since the 1980s, when neuroscientists began identifying these protein tangles, researchers have discovered that other brain diseases have their own tangled-protein signatures.
“Each of these diseases has a unique protein tangle, or fibril, associated with it,” said Anthony Fitzpatrick, PhD, principal investigator at Columbia’s Zuckerman Institute. “These proteins associated with diseases have their own shapes and behaviors,” added Dr. Fitzpatrick, also an assistant professor of biochemistry and molecular biophysics at Columbia University Irving Medical Center and a member of Columbia’s Taub Institute for Research on Alzheimer’s Disease and the Aging Brain.
Published today in Cell, the research by Dr. Fitzpatrick and an international team of 22 collaborators reveals a new fibril in diseased brains, one formed by a protein normally busy cleaning cells.
“We have a surprising and provocative result that we hope could have some bearing on managing neurodegenerative diseases,” said undergraduate Andrew Chang, a co-first author on the paper in the Fitzpatrick lab. Drug researchers have long pursued the tangle-forming proteins as targets for new medicines, but this pursuit so far has largely delivered disappointing results.
Fibril-associated diseases, some common and some rare, collectively affect millions of people around the world. Their incidence is slated to increase as the population grows and people live longer. Untangling what is going on in these neurodegenerative diseases has a personal facet for Dr. Fitzpatrick: He lost an uncle to one of them, progressive supranuclear palsy (PSP).
“We have found that a protein called TMEM106B can form fibrils, and this behavior was not known before,” said Xinyu Xiang, formerly a member of the Fitzpatrick lab at the Zuckerman Institute and now a graduate student at Stanford University’s Department of Structural Biology. “This protein is a core component of lysosomes and endosomes, which are organelles that clean up the junk that builds up in our cells as we get older.”
Normally, TMEM106B molecules span the membranes of those waste-management organelles. In a feat of laboratory sleuthing, Fitzpatrick’s team discovered that TMEM106B molecules can split into two fragments. Fragments inside the organelles can then self-assemble into what the researchers suspect could be cell-hobbling fibrils.

A new DNA test, developed by researchers at the Garvan Institute of Medical Research in Sydney and collaborators from Australia, UK and Israel, has been shown to identify a range of hard-to-diagnose neurological and neuromuscular genetic diseases quicker and more-accurately than existing tests.
‘We correctly diagnosed all patients with conditions that were already known, including Huntington’s disease, fragile X syndrome, hereditary cerebellar ataxias, myotonic dystrophies, myoclonic epilepsies, motor neuron disease and more,’ says Dr Ira Deveson, Head of Genomics Technologies at the Garvan Institute and senior author of the study.
The diseases covered by the test belong to a class of over 50 diseases caused by unusually-long repetitive DNA sequences in a person’s genes — known as ‘Short Tandem Repeat (STR) expansion disorders’.
‘They are often difficult to diagnose due to the complex symptoms that patients present with, the challenging nature of these repetitive sequences, and limitations of existing genetic testing methods,’ says Dr Deveson.
The study, published today in Science Advances, shows that the test is accurate, and allows the team to begin validations to make the test available in pathology services around the world.
A patient who participated in the study, John, first realised something wrong when he experienced unusual problems balancing during a ski lesson.