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Published30 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Jacqueline HowardBBC NewsDame Esther Rantzen says a free vote on assisted dying would be top of the agenda if she were PM for a day.”I think it’s important that the law catches up with what the country wants,” the veteran broadcaster told Radio 4’s Today programme.Earlier this year, the 83-year-old announced she had been diagnosed with stage four lung cancer. Dame Esther told the BBC she is currently undergoing a “miracle” treatment to combat the disease. However, if her next scan shows the medication is not working “I might buzz off to Zurich”, where assisted dying is legal and she has joined the Dignitas clinic, she said.She said this decision could be driven in part by her wish that her family’s “last memories of me” are not “painful because if you watch someone you love having a bad death, that memory obliterates all the happy times”.However, if she did travel to Dignitas, that would put “my family and friends in a difficult position because they would want to go with me”, Dame Esther told the programme, “and that means that the police might prosecute them”. Under the law in England and Wales, anyone assisting someone to die or accompanying them abroad to do so can be sentenced to up to 14 years in prison.”We’ve got to do something. At the moment, it’s not really working, is it?” Dame Esther said.Speaking about assisted dying, Dame Esther said people are “given the choice over so many other things, medical and otherwise. Why should you not be given the choice about how you want to go and when you want to go?…”I get all the arguments about… not wanting to be a burden and pressure being applied and all that. But… you can come to the wrong conclusion. “If you just base everything on the worst case scenario, you’ve got to have a look at the advantages as well.”Almost a year on from her diagnosis, Dame Esther told Today she had not expected to live with cancer for so long.”I thought I’d fall off my perch within a couple of months, if not weeks. I certainly didn’t think I’d make my birthday in June, which I did, and I definitely didn’t think I’d make this Christmas, which I am. It appears, although anything can happen,” she said.At the time, Dame Esther said the news had prompted her to express “profound thanks to everyone who has made my life so joyful”.By May, she announced her lung cancer was in stage four, the most advanced stage, which means the cancer has spread beyond the lungs or from one lung to the other.Dame Esther enjoyed a successful TV presenting career which included hosting BBC consumer show That’s Life! for 21 years.She is also known for launching ChildLine in 1986, the first national helpline for children in danger or distress.In 2013, she launched the Silver Line, a charity to help elderly people suffering from isolation and loneliness.More on this storyEsther Rantzen says her lung cancer is stage fourPublished26 MayDame Esther Rantzen diagnosed with lung cancerPublished29 JanuaryProposed Isle of Man assisted dying laws progressPublished31 October

Xavier Becerra, the health and human services secretary, suggested that states were doing far too little to make sure that children were not unfairly denied federal insurance.The Biden administration on Monday warned the governors of nine states of unusually high Medicaid coverage losses among children, suggesting that officials were failing to protect young, low-income Americans while winnowing the program’s rolls.Xavier Becerra, the health and human services secretary, wrote letters to the leaders of the states that had the highest number or percentage of Medicaid coverage losses among children through September, after a federal policy that required states to keep people in the program lapsed.The appeals to state leaders doubled as a call to expand Medicaid under the Affordable Care Act. The letter recipients included Gov. Ron DeSantis of Florida, Gov. Brian Kemp of Georgia and Gov. Greg Abbott of Texas. All three are Republicans who lead states that have not expanded Medicaid and where hundreds of thousands of children have lost coverage this year.The nine states accounted for roughly 60 percent of the decline in enrollment in Medicaid and the Children’s Health Insurance Program, or CHIP, through September, federal health officials said.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

New research suggests that air pollution may contribute to the development or worsening of skin conditions.
The work, which is published in Dermatology and Therapy and led by scientists at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system, points to the need to improve air quality to lower the burden of skin disease, especially for vulnerable communities.
“We were inspired to investigate the relationship between air pollution and skin inflammation after listening to patients who kept telling us that their skin conditions like eczema were particularly bad, and in some cases ‘worse than ever before,’ this summer,” says senior author Arianne Shadi Kourosh, MD, MPH, director of Community Health in the Department of Dermatology at MGH.
“This was strange because typically patients with eczema are more likely to experience worsening symptoms or flares in winter months due to cold dry weather, but we were seeing the opposite: an unusual surge in the summer.”
Kourosh and her colleagues examined Environmental Protection Agency measurements of carbon monoxide levels in the Boston region in the months following the Canadian wildfires of 2023.
They also assessed dermatology clinic visits for dermatitis and eczema at the Mass General Brigham (MGB) hospital system, 300 miles from the wildfires, and compared this information with data from the corresponding months in 2019-2022.
The team observed a notable rise and an atypical summer peak in carbon monoxide levels in the Boston region during 2023. Carbon monoxide concentrations that were an average of 0.22 ppm in the months of May-September in 2019-2022 rose to 0.6 ppm in July of 2023.

This peak correlated with a spike in visits for atopic dermatitis and eczema at dermatology clinics within the MGB hospital system compared with the prior four years.
Exposure to pollutants from wildfires and chronic air pollution can cause cumulative damage to the skin by triggering a stress response that impacts collagen metabolism, promoting premature skin aging and weaking the skin barrier, which leads to more inflammation and damage, Kourosh and colleagues explain.
The researchers noted that airborne particulate matter (a mixture of microscopic pollutants) is more commonly assessed in studies of air pollution, and while it was also higher in Boston during the spike of these dermatitis-related clinic visits (41 ug/m3 in July 2023 versus 6.6 ug/m3 during the year prior), they chose to highlight carbon monoxide due to its atmospheric longevity and usefulness for tracking downstream air pollution during wildfires.
The authors note that their study is retrospective and that correlation does not prove causation. More research will be needed to explore the connections between air pollution and skin problems.
“As wildfire events in North America have been increasing, we must become equipped not only to prevent and extinguish fires, but to also clean or purify our air in order to minimize the negative impacts of these air pollution events on the health of our communities,” says lead author and medical student Kathyana P. Santiago Mangual, BA.
“Such efforts will have the greatest impact on populations that are most vulnerable to the negative effects of air pollution — including low-income communities, older individuals, and children.”
Additional authors include Sarah Ferree, MD, and Jenny E. Murase, MD.

Large language models (LLMs) like ChatGPT and GPT-4 have the potential to assist in clinical practice to automate administrative tasks, draft clinical notes, communicate with patients, and even support clinical decision making. However, preliminary studies suggest the models can encode and perpetuate social biases that could adversely affect historically marginalized groups. A new study by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, evaluated the tendency of GPT-4 to encode and exhibit racial and gender biases in four clinical decision support roles. Their results are published in The Lancet Digital Health.
“While most of the focus is on using LLMs for documentation or administrative tasks, there is also excitement about the potential to use LLMs to support clinical decision making,” said corresponding author Emily Alsentzer, PhD, a postdoctoral researcher in the Division of General Internal Medicine at Brigham and Women’s Hospital. “We wanted to systematically assess whether GPT-4 encodes racial and gender biases that impact its ability to support clinical decision making.”
Alsentzer and colleagues tested four applications of GPT-4 using the Azure OpenAI platform. First, they prompted GPT-4 to generate patient vignettes that can be used in medical education. Next, they tested GPT-4’s ability to correctly develop a differential diagnosis and treatment plan for 19 different patient cases from a NEJM Healer, a medical education tool that presents challenging clinical cases to medical trainees. Finally, they assessed how GPT-4 makes inferences about a patient’s clinical presentation using eight case vignettes that were originally generated to measure implicit bias. For each application, the authors assessed whether GPT-4’s outputs were biased by race or gender.
For the medical education task, the researchers constructed ten prompts that required GPT-4 to generate a patient presentation for a supplied diagnosis. They ran each prompt 100 times and found that GPT-4 exaggerated known differences in disease prevalence by demographic group.
“One striking example is when GPT-4 is prompted to generate a vignette for a patient with sarcoidosis: GPT-4 describes a Black woman 81% of the time,” Alsentzer explains. “While sarcoidosis is more prevalent in Black patients and in women, it’s not 81% of all patients.”
Next, when GPT-4 was prompted to develop a list of 10 possible diagnoses for the NEJM Healer cases, changing the gender or race/ethnicity of the patient significantly affected its ability to prioritize the correct top diagnosis in 37% of cases.
“In some cases, GPT-4’s decision making reflects known gender and racial biases in the literature,” Alsentzer said. “In the case of pulmonary embolism, the model ranked panic attack/anxiety as a more likely diagnosis for women than men. It also ranked sexually transmitted diseases, such as acute HIV and syphilis, as more likely for patients from racial minority backgrounds compared to white patients.”
When asked to evaluate subjective patient traits such as honesty, understanding, and pain tolerance, GPT-4 produced significantly different responses by race, ethnicity, and gender for 23% of the questions. For example, GPT-4 was significantly more likely to rate Black male patients as abusing the opioid Percocet than Asian, Black, Hispanic, and white female patients when the answers should have been identical for all the simulated patient cases.
Limitations of the current study include testing GPT-4’s responses using a limited number of simulated prompts and analyzing model performance using only a few traditional categories of demographic identities. Future work should investigate biases using clinical notes from the electronic health record.
“While LLM-based tools are currently being deployed with a clinician in the loop to verify the model’s outputs, it is very challenging for clinicians to detect systemic biases when viewing individual patient cases,” Alsentzer said. “It is critical that we perform bias evaluations for each intended use of LLMs, just as we do for other machine learning models in the medical domain. Our work can help start a conversation about GPT-4’s potential to propagate bias in clinical decision support applications.”

As the world heats up, and the climate shifts, life will migrate, adapt or go extinct. For decades, scientists have deployed a specific method to predict how a species will fare during this time of great change. But according to new research, that method might be producing results that are misleading or wrong.
University of Arizona researchers and their team members at the U.S. Forest Service and Brown University found that the method — commonly referred to as space-for-time substitution — failed to accurately predict how a widespread tree of the Western U.S. called the ponderosa pine has actually responded to the last several decades of warming. This also implies that other research relying on space-for-time substitution may not accurately reflect how species will respond to climate change over the next several decades.
The team collected and measured ponderosa pine tree rings from across the Western U.S. going as far back as 1900 and compared the trees’ actual growth to how the model predicted the trees should respond to warming.
“We found that space-for-time substitution generates predictions that are wrong in terms of whether the response to warming is a positive or negative one,” said Margaret Evans, a coauthor on the paper and an associate professor in the UArizona Laboratory of Tree-Ring Research. “This method says that ponderosa pines should benefit from warming, but they actually suffer with warming. This is dangerously misleading.”
Their findings are published in the Proceedings of the National Academy of Sciences. U.S. Forest Service ORISE Fellow Daniel Perret is first author and received his tree ring analysis training at the UArizona laboratory through the university’s summer field methods course. This research was part of his doctoral dissertation at Brown University with Dov Sax, a professor of biogeography and biodiversity and coauthor on the paper.
This is how space-for-time substitution works: Every species occupies their preferred range of climate conditions. Scientists have assumed that the individuals growing at the hotter end of that range can serve as an example of what might happen to populations at cooler locations in a warmer future.
The team found that ponderosa pine trees grow at a faster rate at warmer locations. Under the space-for-time substitution paradigm, then, this suggests that as the climate warms at the cool edge of distribution, things should be getting better.

“But in the tree ring data, that’s not what it looks like,” Evans said.
But when the team used tree rings to assess how individual trees responded to changes in temperature, they found that the ponderosa’s were consistently negatively impacted by temperature variability.
“If it’s a warmer-than-average year, they put on a smaller-than-average ring, so warming is actually bad for them, and that’s true everywhere,” she said.
The team suspects that this is happening because the trees can’t adapt fast enough to keep up with the quickly changing climate.
An individual tree and all its rings are a record of the genetics of that specific tree being exposed to different climatic conditions in one year compared to the next, Evans said. But how a species responds as a whole is the result of the slow pace of evolutionary adaptation to the average conditions at a specific location, which are different from another location. Like evolution, migration of better-adapted trees with the changing temperatures could potentially rescue species, but climate change is happening too fast, Evans said.
Beyond temperature, the team also investigated how trees respond to rainfall. They confirmed that more water is always better, whether you look across time or space.
“These spatially based predictions are really dangerous, because the spatial patterns reflect an end point after a long period of time when species have had a chance to evolve and disperse and, ultimately, sort themselves out on the landscape,” Evans said. “But that’s just not how climate change works. Unfortunately, the trees find themselves in a situation where change is happening faster than the trees can adapt, which is really putting them at risk of going extinct. It’s a word of caution for ecologists.”

Published13 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Jim ReedHealth reporterThe government has said it is still not in a position to make a final decision on compensation for the victims of the infected blood scandal. Earlier this month, the government lost a key vote designed to speed up the creation of a new body to administer and make payments. Cabinet office minister John Glen said he recognised the anger of victims. But he told the Commons it would be wrong to pre-judge the final report of a public inquiry due next year.”For these reasons, the government is not yet in a position to share any final decisions on compensation,” he said. “However, members across this house have made clear that we must do right by the victims and the government recognises this, and I am personally committed to make sure that we do that.”What is the contaminated blood inquiry?Blood scandal: 1 in 3 infected with HIV was a childHunt says compensation bill may be very largeUp to 30,000 patients were infected with HIV and hepatitis C through contaminated blood products in the 1970s and 1980s. It is thought more than 3,000 people died in what has been described by MPs as the worst treatment disaster in NHS history.The government has said there is a moral case for compensating victims of the scandal, and has made the first interim payments of £100,000 each to 4,000 surviving victims and bereaved partners. On 4 October, MPs narrowly defeated the government in a vote to amend the Victims and Prisoners Bill. That legislation, which still needs to be approved by the House of Lords before becoming law, would mean a new independent body would have to be set up within three months to administer full compensation payments to a wider group of victims and their relatives. Campaigners say that one person affected by the scandal dies every four days, making the speed of compensation key. ‘Significant impact’Speaking in the Commons, Mr Glen said the government was still “working through the implications” of the amendment, adding that a final decision on compensation must consider both the victims of the scandal and the costs to the public sector.”There are a number of technical issues that must be considered that would have a significant impact on public finances,” he said.”This is my highest priority and I will continue to progress this work with all the urgency it deserves.”A new psychological support service would be set up for victims and their families in England, to go live from early summer 2024, he added. Earlier this year, Sir Brian Langstaff, who is chairing the long-running public inquiry into the scandal, called for a full compensation scheme to be set up immediately. Mr Glen repeated that it would be inappropriate for the government to respond until its full findings have been published, a process currently expected to be completed in March 2024. Responding, Labour MP Dame Diana Johnson, who put forward the amendment, said the government’s statement would cause “huge anguish” to victims, and “fuel suspicion” ministers were trying to delay the payments. “Justice delayed again will be justice denied for even more of those infected and affected in this scandal,” she added.The father of the house, Sir Peter Bottomley, one of 22 Conservative MPs who also voted for the amendment, said the government was still not doing enough for victims. “If it’s a question of money… and the cash flow of the government, say so now,” he added. More on this storyWhy the NHS gave thousands HIV-contaminated bloodPublished27 July 2021How 175 British children were infected with HIVPublished6 October 2022

Scientists led by Duke-NUS Medical School in Singapore and the University of California, Los Angeles, (UCLA) in the United States have discovered a new control mechanism that can drive the maturation of human stem cell-derived heart muscle cells, providing fresh insight into the maturation process of heart muscle cells from fetal to adult form.
After birth, heart muscle cells undergo extensive changes to become fully mature adult cells, altering their form, function and physiology. However, the regulatory processes governing this maturation have been poorly understood thus far. For regenerative therapies in particular, this lack of understanding has proven a major limitation as efforts to grow stem cell-derived heart muscle cells have not been successful at producing mature adult cells, capable of restoring or improving heart function.
Publishing in Circulation, the research team used transcriptomic analysis to pinpoint an RNA splicing regulator named RBFox1 that was highly elevated soon after birth in a newborn heart. Analyses of published single-cell data also showed dramatic RBFox1 increase in maturing heart cells.
“This represents the first evidence that RNA splicing control contributes significantly to heart cell maturation,” said lead author Dr Huang Jijun, who performed the preclinical study during his postdoctoral work at UCLA. “While RBFox1 alone may not be sufficient to mature fetal heart muscle cells all the way to fully matured adult cells, our findings uncover a new RNA-based internal network that can substantially drive this maturation process beyond other available approaches.”
By expressing RBFox1 in immature human stem cell-derived heart cells, the researchers saw enhancements in key indicators of maturation, including cell size, sarcomere structure, contraction, calcium handling and oxygen usage. RBFox1 expression also led to the development of characteristic electrical properties seen in adult cells.
Further analyses showed RBFox1 regulated splicing of RNA transcripts linked to heart cell contraction and sarcomere components.
“This work demonstrates for the first time that altering RNA splicing alone can stimulate significant maturation of human stem cell-derived heart cells,” said senior author Professor Wang Yibin, Director of the Cardiovascular & Metabolic Disorders Programme at Duke-NUS. “Our results uncover a promising molecular approach to improve heart cell maturation, which could overcome a major limitation in cardiac regenerative therapy and disease modelling.”
While further research is needed to explore the mechanisms linking RBFox1-mediated RNA splicing with downstream maturation processes and phenotype, the study provides proof-of-concept that modulating RNA splicing can significantly impact heart muscle cell, or cardiomyocyte, maturation. This opens possibilities for regulating maturation that could eventually be translated to therapeutic strategies.

The study brought together researchers from leading research institutions across Singapore and the US. Collaborating groups hail from the Agency for Science, Technology and Research (A*STAR)’s Institute of Molecular and Cell Biology in Singapore, and Baylor College of Medicine, Forcyte Biotechnologies, the Greater Los Angeles VA Healthcare System, Meharry Medical College, the Stanford Cardiovascular Institute, the University of Cincinnati, the University of North Carolina, and Vanderbilt University School of Medicine in the US.
“Duke-NUS’ partnerships with leading global institutions continue to foster impactful translational research that advances scientific knowledge and ultimately improves clinical outcomes for patients,” said Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS. “This study’s findings provide a new understanding of the intrinsic regulatory network controlling heart cell maturation and reveal a promising molecular strategy that could potentially be harnessed to progress cell-based therapies and cardiac regenerative medicine.”
Moving forward, the researchers will investigate how RBFox1 coordinates splicing to direct the functional and morphological changes underlying maturation. Their long-term aim is to identify druggable targets that can boost heart cell maturation efficiency for regenerative medicine use.

With more of us looking for alternatives to eating animals, new research has found a surprising environmentally friendly source of protein — algae.
The University of Exeter study has been published in The Journal of Nutrition and is the first of its kind to demonstrate that the ingestion of two of the most commercially available algal species are rich in protein which supports muscle remodeling in young healthy adults. Their findings suggest that algae may be an interesting and sustainable alternative to animal-derived protein with respect to maintaining and building muscle.
Researcher Ino Van Der Heijden from the University of Exeter said: “Our work has shown algae could become part of a secure and sustainable food future. With more and more people trying to eat less meat because of ethical and environmental reasons, there is growing interest in nonanimal-derived and sustainably produced protein. We believe it’s important and necessary to start looking into these alternatives and we’ve identified algae as a promising novel protein source.”
Foods rich in protein and essential amino acids have the capacity to stimulate muscle protein synthesis, which can be measured in the laboratory by determining the incorporation of labelled amino acids into muscle tissue proteins and translated to a rate over time. Animal-derived protein sources robustly stimulate resting and post-exercise muscle protein synthesis.
However, because animal-based protein production is associated with increasing ethical and environmental concerns, it’s now been discovered that an intriguing environmentally friendly alternative to animal-derived protein is algae. Cultivated under controlled conditions, spirulina and chlorella are the two most commercially available algae that contain high doses of micronutrients and are rich in protein. However, the capacity of spirulina and chlorella to stimulate myofibrillar protein synthesis in humans remains unknown.
To bridge the knowledge gap, University of Exeter researchers assessed the impact of ingesting spirulina and chlorella, compared with an established high-quality nonanimal-derived dietary protein source (fungal-derived mycoprotein) on blood amino acid concentrations, as well as resting and post-exercise myofibrillar protein synthesis rates. Thirty-six healthy young adults participated in a randomized, double-blind trial. Following a bout of one-legged resistance leg exercise, participants ingested a drink containing 25 grams of protein from fungal-derived mycoprotein, spirulina or chlorella. Blood and skeletal muscle samples were collected at baseline and during a four-hour post-feeding and post-exercise period. Blood amino acid concentrations and myofibrillar protein synthesis rates in rested and exercised tissue were assessed.
Protein ingestion increased blood amino acid concentrations, but most rapidly and with higher peak responses following consumption of spirulina compared with mycoprotein and chlorella. Protein ingestion increased myofibrillar protein synthesis rates in both rested and exercised tissue, with no differences between groups, but with higher rates in exercised compared with rested muscle.
This study is the first of its kind to demonstrate that ingestion of spirulina or chlorella robustly stimulates myofibrillar protein synthesis in resting and exercised muscle tissue, and to an equivalent extent as a high-quality nonanimal derived counterpart (mycoprotein).
In a companion commentary, Lucy Rogers and Professor Leigh Breen from the University of Birmingham highlight the strengths and utility of these novel findings, while identifying paths forward for future research that focuses on diverse populations such as older adults.

Scientists from Necker-Enfants Malades Hospital (AP-HP), the Institut Pasteur, Université Paris Cité, Inserm, Université Paris-Est Créteil and the Alfort National Veterinary School, coordinated by Professor Marc Eloit and Dr. Anne Jamet in collaboration with Dr. Jacques Fourgeaud and Beatrice Regnault, studied the role of global genetic characterization of samples (or non-targeted metagenomics) using next-generation sequencing (mNGS) in diagnosing infections. The results of the study were published on December 1, 2023 in the journal Lancet Microbe.
The identification of microorganisms involved in infection is a major challenge in ensuring that patients receive optimal treatment. Recent epidemics have shown the importance of a tool capable of detecting new or unexpected pathogens and those with rapidly evolving genomes. Currently, the search for infectious agents is mostly ‘targeted’ and requires prior knowledge of the possible causes of infection. In many cases however, no microorganism is identified by first-line testing and the cause of the infection remains unknown, leading to suboptimal treatment.
Metagenomics1 using next-generation sequencing (mNGS) can identify a wide range of pathogens, including rare or novel microorganisms. This study aims to improve use of this innovative microbial identification technique, which remains complex and costly for hospital laboratories as it requires cross-disciplinary skills ranging from specific sample preparation to bioinformatics analysis of a large number of sequences. The hospital team drew on the technical and IT skills of the Institut Pasteur’s Pathogen Discovery Laboratory2 and worked to make mNGS available within the AP-HP and to practitioners in healthcare centers in mainland France and overseas.
In this study, 742 samples were collected for mNGS analysis from 523 patients between October 29, 2019 and November 7, 2022. Samples were accompanied by a mandatory prescription form completed by the physician, indicating the level of clinical suspicion of infection.
The results relate to a panel whose initial suspicion of infection was either high (63%) or low (37%). In 117 patient samples where infection was strongly suspected — i.e. 25% of samples where infection was strongly suspected according to the practitioners’ preliminary assessment — causative or potentially causative pathogens were detected.
The diagnostic yield of mNGS was particularly high in immunocompromised patients and in patients with neurological disorders where brain biopsies were available. In fact, mNGS more easily detects a causative or potentially causative pathogenic virus in brain biopsies than in cerebrospinal fluid, which is traditionally used because it is easier to obtain. Furthermore, the study showed that stool analyses could be used to investigate not only digestive disorders, but also hepatitis and various neurological symptoms.
In addition, the clinical performance of mNGS compares favorably to conventional microbiology. Together with future studies, the results of this prospective observational study will help to define the role of mNGS in decision making relating to diagnosis and treatment.

“The Microbiology Laboratory (Prof. Leruez-Ville), in conjunction with the Department of Infectious and Tropical Diseases (Prof. Lortholary and Prof. Lecuit) and the Pediatric Immunohematology and Rheumatology Department (Prof. Quartier dit Maire and Prof. Neven) at Necker-Enfants Malades Hospital (AP-HP), has developed extensive expertise in the management of immunocompromised patients prone to infections caused by unusual microorganisms. The Institut Pasteur’s Pathogen Discovery Laboratory2, which was led by Prof. Marc Eloit at the time of the study, had already optimized the use of high-throughput sequencing for pathogen discovery by developing the technique for both sample preparation methods and bioinformatics analysis tools. This collaboration between Necker-Enfants Malades (AP-HP) and the Institut Pasteur was therefore well placed to identify novel causes of infection in cases where conventional techniques were missing diagnoses,” explains Dr. Anne Jamet, the study’s final author, who is head of mNGS at Necker-Enfants Malades Hospital (AP-HP) and a researcher at the Institut Necker-Enfants Malades (AP-HP).
“Our instincts have translated into reliable diagnoses in everyday practice as well as several noteworthy discoveries, including the identification of a new virus responsible for hepatitis,” adds Dr. Jacques Fourgeaud, first author of the study and lead virologist for mNGS at Necker-Enfants Malades Hospital (AP-HP).
“This sequencing-based tool is now indispensable for diagnosing patients with a suspected infection. We are now using it earlier and earlier in severe cases, particularly those involving the brain, and in immunocompromised adults and children,” says Prof. Olivier Lortholary, an infectious diseases specialist who is head of the Department of Infectious and Tropical Diseases at Necker-Enfants Malades Hospital (AP-HP) and co-author of the study.
“We’re delighted to be able to contribute to better medical care, while at the same time increasing our knowledge of infectious diseases,” adds Prof. Marc Eloit, co-last author of the study, who led the Pathogen Discovery Laboratory2 until September 2023 and is now a visiting researcher at the Institut Pasteur. The study also provides an insight into the future of infection diagnostics. “The microorganisms we identify with the Necker microbiology laboratory will enable us to develop new tools to make sequencing technology faster and more accessible for front-line microbiological analysis while enhancing its potential for the discovery of new human pathogens,” says co-author Philippe Pérot, a research engineer in the Institut Pasteur’s Pathogen Discovery Laboratory2 and lead for mNGS at the Institut Pasteur.
The study was funded by Necker-Enfants Malades Hospital (AP-HP) and the Institut Pasteur.
1 Study of all genomes from a single environment and interactions between them
2 The Institut Pasteur’s Pathogen Discovery Laboratory was led by Prof. Marc Eloit until August 31, 2023. Dr. Nolwenn Dheilly took over as head of the laboratory on September 1, 2023.

Led by Aoxing Liu and senior authors Melinda Mills, Andrea Ganna and an international team, the study examined the link between 414 early-life diseases and lifetime childlessness in over 2.5 million individuals born in Finland and Sweden.
In many Western European and East Asian countries, up to 15-20% of individuals born around 1970 are now childless. Although multiple social, economic and individual preferences have been studied, there has been limited research examining the contribution of different diseases to being childless over a lifetime, particularly those diseases with onset prior to the peak reproductive age.
Dr Aoxing Liu, lead author of the study and Postdoctoral researcher at the University of Helsinki’s Institute for Molecular Medicine in Finland (FIMM) said, ‘Various factors are driving an increase in childlessness worldwide, with postponed parenthood being a significant contributor that potentially heightens the risk of involuntary childlessness. Our study is the first to systematically explore how multiple early-life diseases relate to lifetime childlessness and low parity in both men and women.’
Using nationwide registers, the researchers analysed information on 414 early-life disease diagnoses for 1.4 million women born between 1956-1973 and 1.1 million men born between 1956-1968. All were alive at the age of 16, did not emigrate, and had mostly finished their reproductive years by the end of 2018 (defined as age 45 for women, and age 50 for men).
The study’s main analyses focused on 71,524 full-sister and 77,622 full-brother pairs who exhibited differences in their childlessness status. Interestingly, the association between disease and childlessness was more alike between childless individuals and their siblings who had only one child, in comparison to those with more children.
Out of the 74 diseases significantly associated with childlessness in at least one sex, including the 33 shared among women and men, more than half of these were mental-behavioural disorders. In addition, several novel associations between disease and childlessness were discovered such as autoimmune and inflammatory diseases. A full list of the results can be found on this interactive dashboard.
A quarter of the 1.1 million men studied were childless compared to 16.6% of the 1.4 million women. Individuals with lower educational attainment in Finland and Sweden were more likely to be childless compared to the general population, and an individual’s childless status was notably linked to their parents’ level of education.

The researchers also observed significant gender differences in the relationships between diseases and childlessness. For example, schizophrenia and acute alcohol intoxication exhibited stronger associations with childlessness in men, while diabetes-related diseases and congenital anomalies showed stronger associations among women.
Sex differences were noticeable in the age of disease onset, with stronger associations earlier on for women diagnosed between the ages of 21-25, and later for men diagnosed at the age of 26-30. For instance, women diagnosed with obesity experienced higher levels of childlessness if they received their initial diagnosis between the ages of 16-20, compared to those diagnosed at a later age.
Professor Melinda Mills, senior author and Director of the Leverhulme Centre for Demographic Science at Oxford Population Health said, ‘As well as reinforcing demographic research on assortative mating and other socioeconomic factors linked to childlessness, this paper underscores the necessity for interdisciplinary research and enhanced public health emphasis on addressing early-life diseases among both men and women in relation to childlessness.’
The study also revealed that the absence of a partner played a substantial role in the connection between diseases and childlessness, accounting for an estimated 29.3% in women and 37.9% in men. Childless individuals were twice as likely to be single, whilst six diseases in women and 11 in men remained associated with childlessness among partnered individuals.
Associate Professor Andrea Ganna, senior author and FIMM-EMBL group leader at the University of Helsinki’s FIMM concluded, ‘This study reveals a connection between early-life diseases and childlessness, influencing both single and partnered women and men differently. By assessing the role of multiple early-life diseases on childlessness for 2.5 million people across Finland and Sweden, this study paves the way for a better understanding of how disease contributes to involuntary childlessness and the need for improved public health interventions.’
The study acknowledges the need for additional data to distinguish between the impacts of voluntary and involuntary childlessness, and further research to enhance the generalisability of results beyond Nordic countries and to more recent cohorts with evolving treatments, reproductive and partnering practices.