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Published3 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Lisa SummersScotland Health CorrespondentA fatal accident inquiry (FAI) got under way this week into the deaths of three babies, all less than a day old, in Lanarkshire. The death of a baby is an event no parent should endure, let alone in circumstances where – if there were different decisions, procedures, or knowledge – that baby may have survived.To then have the details of that personal tragedy made public is further trauma that no family would want. Mirabelle Bosch died at just 12 hours old on 2 July 2021 at Wishaw General Hospital.Ellie McCormick died at five hours old on 5 March 2019 at the same hospital.And Leo Lamont was two hours old when he died at Monklands Hospital on 15 February 2019.It is important that these deaths are not brushed off as isolated tragedies, and if there are common failings then they should be investigated to prevent anything like this from happening again.That is why three families who were anticipating a joyous turn in their lives are putting themselves through the distress of reliving their worst nightmare. What is an FAI and why has it been called for?This FAI was called by the Crown Office and Procurator Fiscal Service which has deemed it in the public interest for this inquiry to take place.Mirabelle, Leo and Ellie were all said to have died “in circumstances giving rise to serious public concern”.The purpose of this FAI is not to apportion blame, but to establish what happened and prevent future deaths from happening in similar circumstances. A sheriff will hear evidence, and eventually issue a determination of their findings which can include recommendations. Image source, SpindriftWhat have we learned so far?Sheriff Principle Aisha Anwar, who is leading this inquiry, is sensitive to the immense trauma suffered by each family.While there is no way to avoid the distressing detail of what happened, much of their evidence has been submitted as written affidavits to save them the ordeal of being questioned on it in court. All the parents were in court on the first day of the inquiry, but none have been there since.Although very little is known at this stage, it is clear that a key question families want answered is how and whether potential procedural or system errors contributed to their babies deaths. The inquiry is set out in three chapters, firstly looking at the circumstances around Mirabelle Bosch’s death. Her father Eckhardt, told the inquiry they were “led into a dark tunnel” by “misguided” instructions which gave them a “wrong sense of security”.They had believed everything with the pregnancy was normal, with antenatal checks suggesting the baby was healthy and developing as it should. But the court heard that despite a 31-week scan recording the baby as completely breech, three subsequent midwife examinations recorded it as being in a head down, cephalic position. This is the position that typically allows for the smoothest delivery. Even when Rozelle Bosch’s waters broke suddenly on 30 June 2021 and she was examined in hospital, the midwife sent her home to wait for labour to advance. Mirabelle was considered a “low-risk” pregnancy and midwife Michelle Tannahill told the inquiry this week she saw “no red flags” upon her examination. “Everything I had found that night was within the scope of my practice within midwifery. There wasn’t anything concerning,” she said. The details of what happened next are extremely distressing.Husband Eckhardt Bosch said he still feels the trauma in his body over the night of 1 July. After going into active labour at home, paramedics were called but a catalogue of delays ensued. It took five attempts to call the maternity unit at Wishaw General Hospital before anybody answered the phone, and paramedics were unable to deliver the baby themselves.Mirabelle’s head was stuck and by the time mother and baby were taken to hospital, her chances of survival were very slim. She died hours later in her mother’s arms. The post-mortem later noted that if the breech position had been recognised earlier in the pregnancy, then Rozelle would have likely been classified as a higher risk where a management plan for a hospital birth would have been arranged and the outcome may have been different.The pathologist also concluded if there had not been such a long delays transporting the patient to hospital, she may also have stood a chance of survival. What has still to come?Evidence has been heard from health professionals involved in Mirabelle’s death, with expert witnesses who were not directly involved in the case to follow. The FAI will then examine the deaths of Ellie McCormick and Leo Lamont.At this point there is no indication that health professionals in Mirabelle’s case had not followed the protocols or procedures in place at the time. However, there have been questions about whether software used to record details of the pregnancy may not have alerted those involved of potential risks, or may have some limitations in the information it can hold. Issues around the subjectivity of deciding whether a baby is engaged in early pregnancy, and how clear instructions are to mothers on when they come into hospital, have also been discussed.These areas are likely to be explored further when the inquiry examines the circumstances around the deaths of Leo and Ellie.Speaking to BBC Scotland News, the McCormick family lawyer said they believe Ellie’s death was entirely avoidable.Darren Deery, a specialist in medical negligence law, said: “The family’s understanding is that there were potential defects in the system, in that certain risk factors weren’t highlighted in the way they could, and should, have been.”And had the subsequent midwifery and obstetrics staff been aware of those risks, a different course of action would have been taken and the outcome may well have been different.”Ultimately there will be no blame placed here, but it will look in detail at what happened in each case, considering whether systems were at fault, whether individual or collective errors were involved and it will establish what steps, if any, might be taken to prevent other children dying in similar circumstances.

Data from the St. Jude lifetime cohort study (St. JudeLIFE) revealed that two common biomarkers of cardiac function and damage could better predict cardiomyopathy within five years than routine clinical evaluations in high-risk, asymptomatic childhood cancer survivors. Early detection through screening using these two biomarkers may lead to earlier treatment to prevent and protect against further heart damage. The findings were published today in the Journal of Clinical Oncology.
Cardiomyopathy is often asymptomatic at onset and thus “invisible” to routine clinical evaluations. St. Jude Children’s Research Hospital scientists found that two common biomarkers, global longitudinal strain (GLS) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), could identify survivors with otherwise normal appearing heart function who are at elevated risk of decline in heart muscle function.
“This may be a much more sensitive way to identify childhood cancer survivors that might benefit from intervention at an earlier stage,” said first and corresponding author Matthew Ehrhardt, MD, MS, St. Jude Department of Oncology. “We were somewhat surprised by the magnitude of risk for declining heart function over such a relatively short period in individuals with abnormal GLS and NT-proBNP, suggesting a need for early and effective interventions that we hope will prevent progression to heart failure over time.”
The results showed an increase in predicting asymptomatic heart damage in patients treated with potent anthracycline chemotherapy drugs, such as doxorubicin. The study found that these biomarkers did not improve prediction models in patients who only received radiation. This knowledge may help physicians limit testing to only anthracycline-exposed survivors, saving time and resources while maximizing utility.
“This means doing more for patients at greatest risk while avoiding unnecessary tests for patients who will not benefit from them,” Ehrhardt said.
Two signs point to invisible heart problems
The key to helping survivors with asymptomatic cardiomyopathy is to detect dysfunction early. Cardiac function is typically assessed using echocardiograms, which look at the volume of blood pumped through part of the heart. The most common measure of that volume is called left ventricular ejection fraction. Many childhood cancer survivors appear to have a normal ejection fraction, only to later develop cardiomyopathy. Findings showed that even in survivors with normal ejection fraction, abnormal GLS and NT-proBNP improved the ability to predict cardiomyopathy risk.

“A survivor with a normal ejection fraction at baseline with abnormal ranges of both biomarkers was at a fourfold increased risk for a worsening ejection fraction in the next five years,” Ehrhardt said.
GLS is an additional measure of heart function obtained from an echocardiogram. GLS is more sensitive for detecting cardiac muscle injury than the traditionally reported ejection fraction. It is a software-derived mathematical estimation of the heart muscle fibers’ ability to contract, rather than the more rudimentary measure of ejection fraction, or blood volume pumped at a specific time. An institution that performs echocardiograms to measure ejection fraction can theoretically also routinely measure GLS.
NT-proBNP is a serum biomarker, a chemical released into the bloodstream in greater quantities when the heart is injured or overworked. It is frequently used in adult cardiac patients to identify potential heart injury and is thus widely available, though its application in pediatric oncology is relatively novel.
Practical measures to predict and protect the heart earlier
“One of the promising aspects of our findings is that both of these measures are readily available and, therefore, have the potential to impact care more immediately. Most cardiologists are already using GLS,” Ehrhardt said, “and NT-proBNP has been around for a long time.”
Together, these two common and easy-to-implement measures may help identify survivors at elevated risk of cardiomyopathy earlier, leading to earlier therapeutic interventions. Early detection helps protect against cardiac damage in adults with other diseases; it may extend the same benefits to childhood cancer survivors.

“The exciting part of this study is that it potentially helps to identify a population that we would have otherwise looked at and said, ‘You’re at risk for abnormal heart function, but everything looks good today. We’ll reevaluate your heart in two to five years,'” Ehrhardt said. “Whereas now we have reason to believe those with abnormal biomarkers are a particularly high-risk group that may benefit from closer follow-up or more proactive interventions to reduce risk. The findings set the stage for future studies evaluating novel screening and early intervention strategies that we hope will ultimately improve survivors’ cardiac health and well-being.”
Authors and funding
The study’s other authors are Qi Liu, University of Alberta; Isaac B. Rhea, University of Tennessee Health Science Center; Daniel Mulrooney, Stephanie Dixon, John Lucas, Yadav Sapkota, Kyla Shelton, Kirsten Ness, Deo Kumar Srivastava, Aaron McDonald, Leslie Robison, Melissa Hudson, Yutaka Yasui and Gregory Armstrong, of St. Jude.
The study was supported by grants from the National Cancer Institute (Cancer Center Support (CORE) grant (P30CA21765), U01CA195547 and R01CA216354) and ALSAC, the fundraising and awareness organization of St. Jude.

One of the biggest barriers to regenerative medicine is immunological rejection by the recipient, a problem researchers at the University of Arizona Health Sciences are one step closer to solving after genetically modifying pluripotent stem cells to evade immune recognition. The study “Engineering Human Pluripotent Stem Cell Lines to Evade Xenogeneic Transplantation Barriers” was published in Stem Cell Reports today.
Pluripotent stem cells can turn into any type of cell in the body. The findings offer a viable path forward for pluripotent stem cell-based therapies to restore tissues that are lost in diseases such as Type 1 diabetes or macular degeneration.
“There has been a lot of excitement for decades around the field of pluripotent stem cells and regenerative medicine,” said principal investigator Deepta Bhattacharya, PhD, a professor in the UArizona College of Medicine — Tucson’s Department of Immunobiology. “What we have learned from the experiences of organ transplantation is that you have to have matched donors, but the person receiving the transplant often still requires lifelong immune suppression, and that means there is increased susceptibility to infections and cancer. We’ve been trying to figure out what it is that you need to do to those stem cells to keep them from getting rejected, and it looks like we have a possible solution.”
To test their hypothesis, Bhattacharya and the research team used CRISPR-Cas9 technology, “genetic scissors” that allow scientists to make precise mutations within the genome at extremely specific locations.
Using human pluripotent stem cells, the team located the specific genes they believed were involved in immune rejection and removed them. Prior research into pluripotent stem cells and immune rejection looked at different parts of the immune system in isolation. Bhattacharya and his colleagues from The New York Stem Cell Foundation Research Institute, St. Jude Children’s Research Hospital and the Washington University School of Medicine opted to test their genetically modified stem cells in a complete and functional immune system.
“The immune system is really complicated and there are all sorts of ways it can recognize and reject things,” said Bhattacharya, a member of the UArizona Cancer Center and the BIO5 Institute who also serves on the UArizona Health Sciences Center for Molecular and Immunological Therapies advisory council.
“Transplantation across species, across the xenogeneic barrier, is difficult and is a very high bar for transplantation. We decided if we could overcome that barrier, then we could start to have confidence that we can overcome what should be a simpler human-to-human barrier, and so that’s basically what we did.”
The research team tested the modified stem cells by placing them into mice with normal, fully functioning immune systems. The results were promising — the genetically engineered pluripotent stem cells were integrated and persisted without being rejected.

“That has been the holy grail for a while. You might actually have a chance of being able to perform pluripotent stem cell-based transplants without immune suppressing the person who is receiving them. That would be an important advance, both clinically and from the simple standpoint of scale,” Bhattacharya said. “You wouldn’t have to make individualized therapies for every single person — you can start with one pluripotent stem cell type, turn it into the cell type you want and then give it to almost anyone.”
The next steps, Bhattacharya said, include testing the genetically modified pluripotent stem cells in specific disease models. He is already working with collaborators at The New York Stem Cell Foundation and the Juvenile Diabetes Research Foundation to test the technology in animal models for Type 1 diabetes.
“We needed to overcome the immune system first. The next steps are how do we use these cells?” Bhattacharya said. “We set the bar pretty high for our study and the fact that we were successful gives us some confidence that this can really work.”
Bhattacharya also is the co-founder of startup Clade Therapeutics in Boston, which licensed the technology through Tech Launch Arizona, the University of Arizona’s commercialization arm. Clade Therapeutics is establishing a robust cellular platform using stem cell-derived immune cells for the treatment of cancer and autoimmune diseases. The company said it hopes to begin clinical trials by the end of the year.

Compared to adult cancers, pediatric cancers often have distinctive genetic causes. This means there is an opportunity to develop pediatric-focused diagnostic strategies and treatments. Research by St. Jude Children’s Research Hospital published today in Nature Genetics clarifies the genomic landscape of pediatric acute myeloid leukemia (pAML). The work offers novel insight into this cancer’s causes and unique biological characteristics.
The findings establish 23 distinct molecular categories (including 12 categories not covered by the current classification systems) that can be used to classify cases of pAML on an individual basis. This marks a vital step towards understanding the molecular background and improving treatment strategies in the future. The classification of these cancers and appreciation of their uniqueness is not just a helpful tool for doctors to diagnose patients more accurately. It is also critical to identify the most effective therapeutic route and to ultimately save lives.
Identifying the blind spot
Just over 4 per every 100,000 people develop AML yearly; the vast majority are adults. This conceals the effect of pediatric cases, which account for about 500 new cases each year. Due to this, a disparity in how we understand this cancer has grown. “Most of what we know about classifications of AML really comes from the adult field,” said Jeffery Klco, MD, PhD, St. Jude Department of Pathology. “AML is more common in adults than it is in children.”
Klco, along with first authors Masayuki Umeda, MD, PhD, and Jing Ma, PhD, first demonstrated the unique features of pAML in 2022 with the discovery of a novel alteration in the UBTF gene.
“That put forth a new entity in pediatric AML that had not been described before,” explained Klco. “We decided to take a deeper dive into the overall classification of pediatric AML, recognizing that there are very significant differences between AML in adults and kids.”
To do this, they amassed a cohort of 887 unique pAML cases and examined what was driving the cancers through transcriptome and gene profiling.

“A lot of the types of AML that we see here at St. Jude, you just don’t see in adults,” Klco emphasized.
AML classification provides biological insight and potential clinical guidance
The reasons why different features give rise to AML in children and adults have yet to be fully understood. The normal accumulation of mutations during aging may explain many adult AML cases. In contrast, fusion oncoproteins, aberrant proteins resulting in the fusion of two separate genes, are major drivers for many pAML cases and were shown to account for over 70% of cases in this new study. Although each molecular category has a unique driver, some show very similar transcriptional and mutational profiles, which stood out to the researchers. “Some categories show very similar transcriptional profiles, indicating that the background biology is similar and can be potentially treated by similar drugs,” said Umeda.
This work offers a clear path forward for clinicians to identify distinct pAML sub-types and for larger collaborative groups to define cancer more accurately. “The World Health Organization [WHO] issued new classifications for hematological cancers in 2022, mostly based on adults,” Klco explained. “We recognized that many of the recurrent alterations we found in pAML aren’t even mentioned. Some of these sub-types have a significant impact on outcomes.”
Correct classification will allow clinicians worldwide to understand their pAML patients better and offer guidance to treat cases as low-risk or high-risk. In fact, through their analysis, they determined a strong association between the new sub-types and clinical outcomes. “The study definitely fills a lot of gaps in the current classification of pAML,” Ma confirmed. “It provides a risk stratification strategy that we hope will provide clinicians with a simpler road to accurate diagnosis and optimal treatment in the future.”
Authors and funding
The study’s other authors include Tamara Westover, Yonghui Ni, Guangchun Song, Jamie Maciaszek, Michael Rusch, Delaram Rahbarinia, Scott Foy, Michael Walsh, Priydarshini Kumar, Yanling Liu, Yiping Fan, Gang Wu, Xiaotu Ma, Lu Wang, Jeffrey Rubnitz, and Stanley Pounds of St. Jude; Benjamin Huang of the University of California San Francisco, Sharyn Baker of the Comprehensive Cancer Center, The Ohio State University, and Todd Alonzo of Keck School of Medicine, University of Southern California.
The study was supported by grants from The National Institutes of Health (P30 CA021765, Cancer Center Support Grant and Developmental Fund Award and U54 CA243124), the Fund for Innovation in Cancer Informatics, the Burroughs Wellcome Fund, the V Foundation, and ALSAC, the fundraising and awareness organization of St. Jude.

Antibiotic overuse can lead to antibiotic resistance, but classic antibiotic resistance might not completely explain why antibiotics sometimes fail. Sub-populations of bacteria called persister cells are capable of surviving in the presence of lethal doses of antibiotics for prolonged periods. Although persister cells have been intensively researched, evidence linking them to poor patient outcomes has been limited.
Scientists led by UNC School of Medicine microbiologist Brian Conlon, PhD, and Duke School of Medicine infectious diseases fellow Josh Parsons, MD, PhD, have now shown that E. coli can evolve in patients to produce increased persister cells and this leads to increased survival to antibiotics. Publishing their work in the Proceedings of the National Academy of Sciences (PNAS), Conlon and colleagues used a combination of patient data, clinical isolates and animal models to show that persister cells contribute to antibiotic failure when classic antibiotic resistance does not explain such failure.
“For decades, many scientists around the world have studied persister formation, and we have continually been challenged to provide evidence for real-world importance,” said Conlon, senior author and associate professor of microbiology and immunology. “We think our paper is the strongest evidence supporting the importance of persister cells in the clinic.”
Scientists and doctors have been sounded the alarm that overusing antibiotics — especially when doctors are not certain a patient is suffering from a bacterial infection — is making our arsenal of antibiotics less effective, leading to what we call antibiotic resistance, a global concern.
But some scientists have long thought antibiotic failure might not be that simple and that additional factors were required to understand antibiotic treatment failure, particularly where antibiotic resistance was not identified. Some of these scientists study persister cells, which are sub-populations of bacteria that can withstand antibiotics for a prolonged period of time. Despite a wealth of scientific literature on the subject, Conlon said it remained unclear how much, if at all, this persister phenomenon contributed to antibiotic treatment failure in the clinic. Through a collaboration with Duke researchers Josh Thaden, MD, PhD, and Vance Fowler, Jr., MD, Conlon’s lab decided to conduct stepwise research to investigate the possible role of persister cells in antibiotic failure.
Using clinical E. coli bacteremia isolates — bacteria from the blood of patients — Conlon, first author Joshua Parsons, MD, PhD, an infectious diseases fellow at Duke University, and colleagues found that high-persister mutants evolved in patients. The researchers then documented a 100-fold increase in persisters in one such mutant when challenged with the exact antibiotic doctors had used to treat patient from which the E. coli had been isolated.
The mutant bacteria showed no loss of fitness in a mouse infection model and displayed a 10-fold increase in survival following antibiotic challenge.

Importantly, Conlon said his team documented the infections and treatment protocols of patients who had been prescribed antibiotics to clear E. coli infections. In patients who did not clear infection with antibiotics, Conlon said that classical antibiotic resistance was not responsible for the poor outcomes.
“Because of this research, we think persister formation is likely a significant contributor to antibiotic treatment failure in patients,” Conlon said. “Our research strongly suggests that persister formation is an important metric to consider when treating patients with antibiotics.”
He also said that researchers should develop techniques to identify mutants that are likely to respond poorly to antibiotics because such information would influence treatment choices or duration of treatment. Additionally, the development of new therapeutic approaches to target and kill persisters may improve treatment outcomes in patients.
Along with Conlon and Parsons, authors of the PNAS paper are Ashelyn Sidders, Amanda Velez, Michelle Angeles-Solano, and Sarah Rowe at the UNC School of Medicine; Blake Hanson at the University of Texas Health Science Center; Felicia Ruffin, Joshua Thaden, and Vance Fowler Jr. at Duke University; and Cesar Arias at Cornell University.

Restricting calories is known to improve health and increase lifespan, but much of how it does so remains a mystery, especially in regard to how it protects the brain. Buck scientists have uncovered a role for a gene called OXR1 that is necessary for the lifespan extension seen with dietary restriction and is essential for healthy brain aging.
“When people restrict the amount of food that they eat, they typically think it might affect their digestive tract or fat buildup, but not necessarily about how it affects the brain,” said Kenneth Wilson, Ph.D., Buck postdoc and first author of the study, published online on January 11, 2024 in Nature Communications. “As it turns out, this is a gene that is important in the brain.”
The team additionally demonstrated a detailed cellular mechanism of how dietary restriction can delay aging and slow the progression of neurodegenerative diseases. The work, done in fruit flies and human cells, also identifies potential therapeutic targets to slow aging and age-related neurodegenerative diseases.
“We found a neuron-specific response that mediates the neuroprotection of dietary restriction,” said Buck Professor Pankaj Kapahi , Ph.D., co-senior author of the study. “Strategies such as intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of this gene to mediate its protective effects.”
“The gene is an important brain resilience factor protecting against aging and neurological diseases,” said Buck Professor Lisa Ellerby, Ph.D., co-senior author of the study.
Understanding variability in response to dietary restriction
Members of the team have previously shown mechanisms that improve lifespan and healthspan with dietary restriction, but there is so much variability in response to reduced calories across individuals and different tissues that it is clear there are many yet to be discovered processes in play. This project was started to understand why different people respond to diets in different ways.

The team began by scanning about 200 strains of flies with different genetic backgrounds. The flies were raised with two different diets, either with a normal diet or with dietary restriction, which was only 10% of normal nutrition. Researchers identified five genes which had specific variants that significantly affected longevity under dietary restriction. Of those, two had counterparts in human genetics.
The team chose one gene to explore thoroughly, called “mustard” (mtd) in fruit flies and “Oxidation Resistance 1” (OXR1) in humans and mice. The gene protects cells from oxidative damage, but the mechanism for how this gene functions was unclear. The loss of OXR1 in humans results in severe neurological defects and premature death. In mice, extra OXR1 improves survival in a model of amyotrophic lateral sclerosis (ALS).
The link between brain aging, neurodegeneration and lifespan
To figure out how a gene that is active in neurons affects overall lifespan, the team did a series of in-depth tests. They found that OXR1 affects a complex called the retromer, which is a set of proteins necessary for recycling cellular proteins and lipids. “The retromer is an important mechanism in neurons because it determines the fate of all proteins that are brought into the cell,” said Wilson. Retromer dysfunction has been associated with age-related neurodegenerative diseases that are protected by dietary restriction, specifically Alzheimer’s and Parkinson’s diseases.
Overall, their results told the story of how dietary restriction slows brain aging by the action of mtd/OXR1 in maintaining the retromer. “This work shows that the retromer pathway, which is involved in reusing cellular proteins, has a key role in protecting neurons when nutrients are limited,” said Kapahi. The team found that mtd/OXR1 preserves retromer function and is necessary for neuronal function, healthy brain aging, and lifespan extension seen with dietary restriction.
“Diet is influencing this gene. By eating less, you are actually enhancing this mechanism of proteins being sorted properly in your cells, because your cells are enhancing the expression of OXR1,” said Wilson.

The team also found that boosting mtd in flies caused them to live longer, leading researchers to speculate that in humans excess expression of OXR1 might help extend lifespan. “Our next step is to identify specific compounds that increase the levels of OXR1 during aging to delay brain aging,” said Ellerby.
“Hopefully from this we can get more of an idea of why our brains degenerate in the first place,” said Wilson.
“Diet impacts all the processes in your body,” he said. “I think this work supports efforts to follow a healthy diet, because what you eat is going to affect more than you know.”
Kapahi is founder and a member of the scientific advisory board at Juvify Bio. The other authors have no conflicts of interest.

A U.N.-affiliated panel said the territory could tip into famine very soon. International laws to protect people from human-made famines offer little help.The number of people facing possible starvation in the Gaza Strip in the coming weeks is the largest share of a population at risk of famine identified anywhere since a United Nations-affiliated panel created the current global food-insecurity assessment 20 years ago.After Hamas’s surprise attack on Israel on Oct. 7, Israel responded with air and ground assaults and a sealing of the territory, which have left the 2.2 million people who live there deprived of sufficient food, water and supplies. The U.N. has concluded that without significant intervention, Gaza could reach the level of famine as soon as early February.Limited amounts of food and other aid are entering Gaza from Israel and Egypt at border points with rigorous inspections; the ongoing bombardment and ground fighting make distribution of that aid extremely difficult.Scholars of famine say it has been generations since the world has seen this degree of food deprivation in warfare.“The rigor, scale and speed of the destruction of the structures necessary for survival, and enforcement of the siege, surpasses any other case of man-made famine in the last 75 years,” said Alex de Waal, an expert on humanitarian crises and international law at Tufts University who wrote “Mass Starvation: The History and Future of Famine.”The situation in Gaza is the latest in a series of recent crises that have reversed progress against famine. Mass death from starvation declined steadily from the 1980s well into the 21st century. But over the past seven years, food crises associated with conflict (such as those in Yemen, Syria and the Tigray region of Ethiopia) and those stemming from environmental conditions and climate change (such as in Somalia) have resulted in the loss of more than a million lives.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? 

Nutrition experts say the progression from hunger to severe malnutrition can be rapid, especially in children.A panel of experts affiliated with the United Nations has warned that the population of the Gaza Strip is at imminent risk of famine, with more than 90 percent of its 2.2 million people facing “acute food insecurity” and a quarter of the population experiencing “catastrophic levels of hunger.”Even before the war between Israel and Hamas, nearly 70 percent of Gazans were dependent on humanitarian assistance for food because the territory has been under Israeli and Egyptian blockade since 2007. Now, only 20 to 30 percent of what people there need is being permitted over the border into Gaza, according to the World Food Program. The lack of electricity and fuel and the impossibility of moving around safely have compounded the challenges of producing food or getting it to people. Most people are going a day or longer without eating, the expert panel said.As in a vast majority of other food crises the panel, the Famine Review Committee, has assessed in the 20 years since it was created, the situation in Gaza is not environmental but human-made. But Gaza is unusual for the speed with which people have been pushed into malnutrition.In interviews, nutrition experts and doctors described what can happen when people can’t get food.Children often fail firstChildren, pregnant and lactating women, people with medical conditions and older adults typically succumb first to acute malnutrition. How long they can survive under conditions of extreme hunger will vary.“It depends on the age of the person,” said Zita Weise Prinzo, senior nutritionist with the World Health Organization. “It depends on their health status. It depends on whether they have access to liquids, or to some sort of food, even if it doesn’t cover all the nutrient needs.”UNICEF, the humanitarian aid organization that focuses on children, is particularly concerned about infants, said Anuradha Narayan, the agency’s senior adviser on child nutrition in emergencies. Before the war, about 60 percent of Gazan infants were formula-fed. Their families now have little or no access to any food supply for them.“We know that there are many families who are probably unable to feed their children with infant formula,” she said.For families who have found formula, the challenge is getting clean water to make it; an estimated 1.6 liters of drinking water (versus the minimum of 15 liters per day recommended by the W.H.O.) are available per person in Gaza now.Palestinians displaced by Israeli bombardment waited for water at a makeshift tent camp in the Muwasi area of southern Gaza.Fatima Shbair/Associated PressProgression to severe malnutrition is fastMs. Narayan said the agency estimated that 7,000 to 8,000 children are so severely malnourished that they are at risk of death without immediate treatment, but the active conflict in Gaza was making it difficult for aid agencies to evaluate the situation.“We expect that those numbers can go up pretty dramatically in the next two to three weeks,” she said.Ms. Narayan said that in her work in other food security crises, such as in Ethiopia, it was typical to see a child fall ill and progress to severe malnutrition and wasting within days.For Gaza, she said, “It’s harder to predict but if there is nearly no food to feed young children, and illness involved, I would say it could be exactly the same. You go from being reasonably OK to being on some level of malnutrition, maybe not severely wasted, but still wasted, within a span of a few days. Particularly for the young, less than 2 years old, for sure that is likely to be the case.”The trajectory for people with some access to food would be different, said Dr. Stanley Zlotkin, a professor of nutrition at the University of Toronto and an expert on the effects of critical food shortage. An adult may be able to survive for an extended period with only intermittent access to calories or with only foods that offer limited nutrients, he said. In a situation like Gaza’s, where there is still sporadic availability of some food, most adults would be able to survive for some time, but that would not be enough for children to prevent a progression to malnutrition.What happens in the bodyA malnourished body first burns fat reserves, said Heather Stobaugh, an expert on nutrition and emergencies with the aid agency Action Against Hunger, until those are depleted. Then, “The body will resort to using muscle, and eventually vital organs will begin to break down,” she said. “In the most severe forms of malnutrition, immune systems are weakened and vital organs actually start to shrink — the heart, lungs and so on.” “When a child or an adult reaches this point,” she added, “their body is literally wasting away.”Ms. Weise Prinzo said that people in this state minimize energy expenditure. “They stop any movement not necessary for immediate survival, but also within the organs, there are changes in how the heart and liver function,” she said. “They really try to manage, but eventually one or the other of the systems starts to fail.”At this point, a starving person has a range of physical degradations, including extreme fatigue, an inability to regulate temperature and emotional impairment.“We say ‘acute malnutrition’ and acute means that it could happen in a short period of time,” Dr. Stobaugh said. “It doesn’t always have to be months of a slow degradation.”A destroyed building in Rafah, southern Gaza.Fatima Shbair/Associated PressMalnutrition and disease drive a grim cycleA malnourished person is vulnerable to disease because of a weakened immune system and because pf the conditions of conflict, where there is a lack of clean water and sanitation facilities, and people are often living in crowded shelters.A malnourished body’s defenses — epithelial cells, which make up the surface of the skin and barrier tissues in places such as the gut — break down, and white blood cells malfunction.“Then when you get sick, the body uses whatever protein and energy stores that you have, trying to fight the infection, and that cycle of infection and malnutrition is what rapidly causes the wasting to take place,” Ms. Narayan said. This process is more rapid in children, she said.Dr. Zlotkin said disease spreads rapidly in situations such as the current one in Gaza, where 90 percent of people have been displaced and are sheltering in tents or other temporary structures, and there are few adequate latrines or washing facilities. Pneumonia and gastrointestinal infections are the main causes of death for malnourished people.“You have outbreaks of illness such as extreme diarrhea in combination with no health care services, no food, no clean water,” Dr. Stobaugh said. “This sort of perfect storm of adverse environmental conditions and health conditions is going to exacerbate the speed with which a body will become malnourished and can ultimately become on the brink of death quite quickly.”

A new, systematic analysis of cancer cells identifies 370 candidate priority drug targets across 27 cancer types, including breast, lung and ovarian cancers.
By looking at multiple layers of functional and genomic information, researchers were able to create an unbiased, panoramic view of what enables cancer cells to grow and survive. They identify new opportunities for cancer therapies in a significant leap towards a new generation of smarter, more effective cancer treatments.
In the most comprehensive study of its kind, researchers from the Wellcome Sanger Institute, Open Targets and their collaborators, pooled together data from 930 cancer cell lines. They then used machine learning methods to find the drug targets that show the most promise for developing new treatments, and the patients who would most benefit from such treatments. This involved assessing the occurrence of these targets in actual patient tumours and linking them to specific biological markers and genetic and molecular features found in the tumours.
The findings, published today (11 January) in Cancer Cell, not only bring researchers one step closer to producing a full Cancer Dependency Map1 of every vulnerability in every type of cancer, but help guide focused efforts to accelerate the development of targeted cancer treatments.
There are many types of cancer that currently lack effective treatments, such as liver and ovarian cancers. Chemotherapy and radiotherapy are effective treatments, but unable to distinguish normal cells from cancerous ones, so can cause damage throughout the entire body with harsh side effects, such as extreme fatigue, nausea and hair loss.
New precision drugs based on the exact genetic mutations that drive the cancer are needed to help the millions of patients diagnosed with some form of cancer each year, responsible for one in six deaths worldwide2. However, drug development has a 90 per cent failure rate3, making it both costly and inefficient.
With over 20,000 potential anti-cancer targets in the genome, determining which are suitable to target for specific types of cancers and patients is a significant challenge.

In this new study, researchers from the Wellcome Sanger Institute and their collaborators set out to narrow down potential drug targets. By analysing data available from the Cancer Dependency Map project, which involved CRISPR technology4 to disrupt every gene inside 930 human cancer lines one at a time, they were able to produce the most comprehensive view of potential new cancer targets to date.
The researchers first identified weaknesses within different cancer types — so-called genetic dependencies, meaning which genes, proteins or cellular processes that cancer cells rely on to survive — that could be harnessed to make new therapies. They then linked those weaknesses to clinical markers to identify patients in which those therapies would be most effective. Finally, they explored how dependency-marker pairs fit into known networks of molecular interactions within cells, providing clues as to how cell biology is disrupted by cancer, and which targets might yield the most effective therapies.
The work provides a clearer understanding of which types of cancer can possibly be treated by existing drug discovery strategies and pinpoint areas where novel and innovative approaches are needed.
The findings underscore the importance of tailoring treatments to the unique characteristics of each cancer, promising more personalised care for patients with fewer side effects in the future.
Dr Francesco Iorio, co-lead author of the study from the Computational Biology Research Centre of Human Technopole, said: “Analysing the largest-ever cancer dependency dataset, we present the most comprehensive map yet of human cancers’ vulnerabilities — their “Achilles heel.” We identify a new list of top-priority targets for potential treatments, along with clues about which patients might benefit the most — all made possible through the design and use of innovative computational and machine intelligence methodologies.”
Dr Mathew Garnett, co-lead author of the study at the Wellcome Sanger Institute and Open Targets, said: “Our work uncovers 370 candidate priority targets for tackling the most prevalent cancers, including breast, lung and colon cancers. This work exploits the latest in genomics and computational biology to understand how we can best target cancer cells. This will help drug developers focus their efforts on the highest value targets to bring new medicines to patients more quickly.”
Dr Marianne Baker, science engagement manager at Cancer Research UK, said: “Two people might have the same type of cancer, but their diseases can behave differently. That is why we need precision medicine. This ambitious work is a compelling example of research informing drug discovery from the start, paving the way for more effective precision cancer therapies. Giving people treatments for their unique cancer can improve the odds of success and help more people affected by cancer live longer, better lives.”

1. The Cancer Dependency Map is an international collaboration between the Wellcome Sanger Institute and the Broad Institute in the United States. The results of the first iteration of the Cancer Dependency Map were published in 2019. The Cancer Dependency Map at the Sanger Institute is a project that aims to assign a dependency to every cancer cell in a patient, which could be exploited to develop new therapies. It is linked with the Open Targets initiative to facilitate new drug target identification. Projects developed by the Open Targets consortium have supported elements of the Cancer Dependency map to facilitate new drug target identification inclusive of this research.
2. https://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293739/
4. CRISPR-CAS9 is a tool used to precisely edit DNA.
These data can be accessed on the Sanger Institute’s Cancer Dependency Map website: https://depmap.sanger.ac.uk/

The repair of damage to genetic material (DNA) in the human body is carried out by highly efficient mechanisms that have not yet been fully researched. A scientific team led by Christian Seiser from MedUni Vienna’s Center for Anatomy and Cell Biology has now discovered a previously unrecognised control point for these processes. This could lead to a new approach for the development of cancer therapies aimed at inhibiting the repair of damaged cancer cells. The research work was recently published in the journal “Nucleic Acids Research.”
GSE1-CoREST is the name of the newly discovered complex, which contains three enzymes that control DNA repair processes and could form the basis for novel cancer therapeutics. “In research, these proteins are already associated with cancer, but not in the context that we have now found,” emphasises Christian Seiser, who led the study in close collaboration with researchers from the Max Perutz Labs Vienna. The new complex was identified as a controller of DNA repair processes using a precise measurement method (affinity purification mass spectrometry). “This also showed that the inhibition of these enzymes can prevent the repair of genetic material and cause the death of cells,” says first author Terezia Vcelkova from MedUni Vienna’s Center for Anatomy and Cell Biology describing a highly desirable effect in tumour cells.
Stopping repair mechanisms
The genetic material, the DNA, is exposed to various harmful influences such as UV light or environmental pollutants on a daily basis. These influences can lead to changes in the DNA sequence, so-called mutations. To repair this damage to genetic material, various highly efficient biochemical repair mechanisms are normally activated. If these processes do not succeed in repairing the damage, programmed cell death (apoptosis) is ultimately initiated to protect against malignant cells.
To ensure their survival, cells react to DNA damage by activating and integrating signalling pathways or signalling cascades. This is achieved in particular through the activation of signalling pathways known as DNA damage response (or DDR). These signalling cascades are responsible for bringing repair factors to the right place in the genome at the right time in order to repair the mutated DNA efficiently and promptly. The control instances and regulators in this interaction are better defined thanks to the current research work. “The effectiveness of the novel cancer therapeutics based on this, which are intended to improve the response of tumour cells to cancer therapies, is now being tested in preclinical studies,” says Christian Seiser about the next steps.