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The DNA carries the genetic information of all living organisms and consists of only four different building blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one of the four nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up millions of times and form the DNA double helix, similar to a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides can be modified to a great extent in the laboratory.
The researchers developed so-called threofuranosyl nucleic acid (TNA) with a new, additional base pair. These are the first steps on the way to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published in the Journal of the American Chemical Society.
Artificial nucleic acids differ in structure from their originals. These changes affect their stability and function. “Our threofuranosyl nucleic acid is more stable than the naturally occurring nucleic acids DNA and RNA, which brings many advantages for future therapeutic use,” said Professor Dr Stephanie Kath-Schorr. For the study, the 5-carbon sugar deoxyribose, which forms the backbone in DNA, was replaced by a 4-carbon sugar. In addition, the number of nucleobases was increased from four to six. By exchanging the sugar, the TNA is not recognized by the cell’s own degradation enzymes. This has been a problem with nucleic acid-based therapeutics, as synthetically produced RNA that is introduced into a cell is rapidly degraded and loses its effect. The introduction of TNAs into cells that remain undetected could now maintain the effect for longer.
“In addition, the built-in unnatural base pair enables alternative binding options to target molecules in the cell,” added Hannah Depmeier, lead author of the study. Kath-Schorr is certain that such a function can be used in particular in the development of new aptamers, short DNA or RNA sequences, which can be used for the targeted control of cellular mechanisms. TNAs could also be used for the targeted transport of drugs to specific organs in the body (targeted drug delivery) as well as in diagnostics; they could also be useful for the recognition of viral proteins or biomarkers.

A team of University of Michigan researchers has successfully modified a naturally occurring chemical compound in the lab, resulting in advanced lead compounds with anti-HIV activity.
Their results, published March 7 in the Journal of Medicinal Chemistry, offer a new path forward in the development of drugs that could potentially help cure — rather than treat — HIV.
Although effective treatments are available to manage HIV, a cure has remained elusive due to the virus’s ability to hide from the immune system, lying dormant in reservoirs of infected cells.
“With most viruses, when people get infected, they get sick for a while and then the immune system kicks in and the virus is cleared,” said Kathleen Collins, professor of microbiology and immunology at the U-M Medical School. “But with HIV, once a patient is infected, that virus will persist for their entire life — meaning they must remain on treatments indefinitely.”
One key to HIV’s ability to remain hidden in patients’ cells is a protein that the virus makes, called Nef. This protein shuts down a system that the cell would normally use to alert the immune system to an infection, thus preventing the immune cells from recognizing and clearing the virus.
Collins and her lab have studied this protein for more than 15 years, investigating how it works and how it can be disabled. She and David Sherman, professor at the U-M Life Sciences Institute, previously discovered that a chemical found in nature can inhibit HIV Nef, allowing the immune system to find and eliminate virally infected cells: a compound called concanamycin A (CMA), which is produced by a soil-derived microorganism.
In its natural form, however, CMA presents several challenges as a potential therapeutic. The first challenge the team had to overcome was supply. While CMA is a naturally occurring compound, the original bacteria that produces it does so in quantities far too small to be useful for testing and modification in the lab.

Another major challenge with developing CMA as an anti-HIV drug is that Nef is not CMA’s primary target.
“CMA’s main job in human cells is to inhibit an enzyme called V-ATPase, which we absolutely do not want to block in this case,” said Sherman, who is also a professor at the U-M College of Pharmacy, Medical School, and College of Literature, Science, and the Arts. “So, we needed to find a way to modify CMA’s activity, widening the effective dosage gap between when it starts to inhibit the target we’re aiming for — HIV Nef — without affecting V-ATPase, its typical cellular target.”
With this latest research, the team has overcome both of these challenges. Using bioengineering, Sherman’s team was able to develop a bacterial strain that increased CMA production 2,000-fold. Synthetic chemists in the lab then created more than 70 new variations of the compound, swapping out different chemical groups, to test for their potency against HIV Nef.
Collins’ lab team ran the new compounds through a battery of tests to measure their toxicity to cells, as well as how they affected the activities of both HIV Nef and V-ATPase.
“Even though we know that CMA is extremely active against the HIV Nef protein, all drugs have side effects,” said Collins, also a professor of internal medicine at the Medical School. “And so we wanted to ensure we’ve done everything we can to minimize the side effect profile of the drug before we consider putting it into an animal or human.”
The team now has several CMA analogs that show high potency in blocking HIV Nef at very low dosage levels, without interrupting off-target effects or causing toxicity in human cells. They caution, however, that several important steps remain before the compounds would be ready for further testing in a clinical setting.
“We are really encouraged, though, because our groups have solved some very important problems,” Sherman said. “We have engineered microorganisms to produce sustainable supplies of the natural product molecules and have really good chemical methods to make new analogs. And we have the methodologies in place to continue tracking the critical toxicity and potency parameters to further reduce off-target effects.”
The research was supported by the National Institutes of Health.
Other study authors are: Morgan McCauley, Matthew Huston, Alanna Condren, Filipa Pereira, Joel Cline, Marianne Yaple-Maresh, Mark Painter, Gretchen Zimmerman, Andrew Robertson, Nolan Carney, Christopher Goodall and Valeri Terry of U-M and Rolf Mu?ller of Hemholtz Institute for Pharmaceutical Research, Germany.

As more people seek to go where no man has gone before, researchers are exploring how forensic science can be adapted to extraterrestrial environments.
A new study by Staffordshire University and the University of Hull highlights the behaviour of blood in microgravity and the unique challenges of bloodstain pattern analysis aboard spacecraft.
Bloodstain expert Zack Kowalske is a Crime Scene Investigator based in Atlanta, USA, and led the study as part his PhD research at Staffordshire University.
“Studying bloodstain patterns can provide valuable reconstructive information about a crime or accident. However, little is known about how liquid blood behaves in an altered gravity environment. This is an area of study that, while novel, has implications for forensic investigations in space,” he commented.
“Forensic science is more than just trying to solve crimes; it additionally has a role in accident reconstruction or failure analysis. With this concept, consider how various forensic disciplines could be utilized in a critical accident onboard a space station or shuttle.”
Experiments were conducted aboard a Zero Gravity Corporation modified Boeing 727 parabolic aircraft. A mixture of 40% glycerin and 60% red food colouring was used, simulating the relative density and viscosity of human blood. Blood droplets were propelled from a hydraulic syringe toward a target during periods of reduced gravity between 0.00 and 0.05 g. From these blood stains, the researchers reconstructed the angle of impact.
Co-author Professor Graham Williams, from the University of Hull, explained: “With the lack of gravitational influence, surface tension and cohesion of blood droplets are amplified. What this means is that blood in space has a higher tendency to stick to surfaces until a greater force causes detachment. Within the application of bloodstain formation, it means that blood drops exhibit a slower spread rate and, therefore, have shapes and sizes that would not be reflective on Earth.

“On Earth, gravity and air drag have a noticeable influence on skewing the calculated angle. The initial hypothesis was that because of the absence of gravity, certain mathematical calculations would be more accurate. However, the amplified effect of surface tension became a predominant factor that caused the calculation to have greater variance, even in the absence of gravity.”
This is the first study relating to the behavior of blood in free flight. With the rate of technological evolution in space exploration, the authors say that the need for reliable forensic science techniques will become increasingly important.
Zack added: “We find ourselves in a new era of forensic science; just as mid-19th century research asked the question of what a bloodstain meant in relation to cause; we are once again at the beginning of new questions that tie in how new environments influence forensic science.
“Astroforensics is a novel subdiscipline that is in its infancy. Broadening the understanding of all forensic sciences in non-terrestrial environments is critical as we expand into a space-faring species. Research is needed, research that spans across all disciplines.”

Leaders of the treatment’s manufacturer, Amylyx, said they would announce their plans for it within eight weeks.One of the few treatments the Food and Drug Administration has approved for amyotrophic lateral sclerosis has failed a large clinical trial, and its manufacturer said Friday that it was considering whether to withdraw it from the market.The medication, called Relyvrio, was approved less than two years ago, despite questions about its effectiveness in treating the severe neurological disorder. At the time, the F.D.A.’s reviewers had concluded there was not yet sufficient evidence that the medication could help patients live longer or slow the rate at which they lose functions like muscle control, speaking or breathing without assistance.But the agency decided to greenlight the medication instead of waiting two years for results of a large clinical trial, citing data showing the treatment to be safe and the desperation of patients with a disease that often causes death within two to five years. Since then, about 4,000 patients in the United States have received the treatment, a powder that is mixed with water and either drunk or ingested through a feeding tube and carries a list price of $158,000 a year.Now, results of the 48-week trial of 664 patients are in, and they showed that the treatment did not work better than a placebo.“We are surprised and deeply disappointed,” Justin Klee and Joshua Cohen, the co-chief executive officers of Amylyx Pharmaceuticals, the treatment’s manufacturer, said in a statement. They said they would announce their plans for the medication within eight weeks, “which may include voluntarily withdrawing” it from the market.“We will be led in our decisions by two key principles: doing what is right for people living with A.LS., informed by regulatory authorities and the A.L.S. community, and by what the science tells us,” Mr. Klee and Mr. Cohen 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? Log in.Want all of The Times? Subscribe.

Eli Lilly’s donanemab was expected to be approved this month, but the agency has decided to convene a panel of independent experts to evaluate the drug’s safety and efficacy.The Food and Drug Administration has decided to delay action on a closely watched Alzheimer’s drug, donanemab, which the agency was widely expected to approve this month. The F.D.A. will instead require donanemab to undergo the scrutiny of a panel of independent experts, the drug’s maker, Eli Lilly and Company, said Friday.“The F.D.A. has informed Lilly it wants to further understand topics related to evaluating the safety and efficacy of donanemab, including the safety results in donanemab-treated patients and the efficacy implications of the unique trial design,” the company said in a statement.The decision is likely to surprise many Alzheimer’s experts, doctors and patients who had expected the medication would soon be on the market. The F.D.A.’s move was startling to the company, which had been planning for the agency to greenlight the drug during the first quarter of this year.“We were not expecting this,” Anne White, an executive vice president of Lilly and president of its neuroscience division, said in an interview. She said that while the F.D.A. often calls on such independent advisory committees when it has questions about drugs, it was unusual to do so “at the end of the review cycle and beyond the action date that the F.D.A. had given us.”The F.D.A. did not say anything publicly about the move, which will delay any decision about whether to approve donanemab until at least later this year. Lilly officials said they expected it would be a few months before the advisory committee holds a hearing.“The F.D.A. did commit to us to move quickly, so we would hope that they would then take action shortly after the advisory committee,” Mrs. White 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? Log in.Want all of The Times? Subscribe.

For some, just a few minutes can quiet the mind.As a child, Josh Patner became accustomed to stepping over his mom, who used to lie down in the kitchen whenever her mother-in-law would call.“My grandmother would talk her ear off,” Mr. Patner, 61, recalled. To cope, his mother would “lie on the floor and hold the phone away from her head.” Mr. Patner’s father, also a fan of the floor, took a 20-minute nap under the family’s piano each night after work.So it is unsurprising, perhaps, that Mr. Patner enjoys floor time at his home in Brooklyn or even at his friend’s places — in part to stretch and soothe his back (he has scoliosis), but also, he says, because it feels calming.“If I know you well enough to sit on your couch, I know you well enough to lie on your floor,” he said.While this is nothing new to Mr. Patner, others are just now catching on to the practice: Posts with the hashtag #floortime have garnered millions of views on TikTok.Lily Bishop, a graduate student in Chicago, made a video showing herself prone on her beige carpet, silently staring at the ceiling, arms spread wide. “I am a floor person to my core,” read the words emblazoned over the clip. “Meeting just ended? Floor. Home from the gym? Floor. Want to take a nap? Floor.”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? Log in.Want all of The Times? Subscribe.

A University of Colorado Department of Medicine faculty member says she and her colleagues have identified the means in which bacteria in the digestive system can break down tryptophan in the diet into an inflammatory chemical that primes the immune system towards arthritis.
The research was co-authored by Kristine Kuhn, MD, PhD, Scoville Endowed Chair and head of the CU Division of Rheumatology. Several of her division colleagues collaborated on the paper, which was published in February in the Journal of Clinical Investigation.
Tryptophan is an essential amino acid found in many protein-rich foods, including meats, fish, dairy products, and certain seeds and nuts. It has many uses in the body, including helping in the production of proteins, muscles, enzymes, and neurotransmitters — the nervous system’s chemical messengers. The body doesn’t make it; we get it from our diet.
Many people think of tryptophan as the ingredient in turkey that supposedly makes us sleepy after a Thanksgiving feast. In fact, researchers say that although tryptophan plays a role in helping to regulate the sleep cycle, the amount that’s in turkey probably isn’t a significant cause of post-dinner drowsiness.
Cause and effect
Kuhn and her associates set out to learn how a substance that often is a force for good in the body is converted into a pathway to inflammatory diseases such as rheumatoid arthritis, which affects about 1% of the population. It can cause painful swelling of the hands and feet, and joint deformities if left untreated.
“It’s been known that the microbiome — the bacteria in our gut — can break down tryptophan into byproducts. Some of those byproducts are anti-inflammatory, but we’ve also associated some inflammatory causes of those products,” Kuhn says. “We’re the first to highlight which products are contributing to inflammation, and how they are doing that.”
She says the new research “builds upon some observations we had in patients with spondyloarthritis — not quite rheumatoid arthritis, but a closely related condition — where we found that changes in the microbiome were associated with increased production of these products called indoles, which are what bacteria make from tryptophan.” Similar changes were observed in arthritis studies involving mice, she says.

“We put mice on antibiotics to wipe out their microbiome, and they didn’t get arthritis, and they didn’t have indole,” she says. “So we said, OK, what if they do have a microbiome and we put them on a diet with little tryptophan? The microbiome can’t break down tryptophan into indole, and the mice didn’t get arthritis. So two different ways, we showed that it’s tryptophan that’s broken down by the microbiome into indole.”
Inflammatory flags
So how does that work? “We found that when indole is present, the mice start to develop autoreactive T-cells that are more inflammatory. They have less of those regulatory T-cells that help maintain balance in the immune system, and they start to develop antibodies that are more pathogenic. We found that the antibodies had flags for being more inflammatory when indole was present.”
The paper concludes that “blockade of indole generation may present a unique therapeutic pathway” for rheumatoid arthritis and spondyloarthritis. That’s all about finding the right path for the body’s tryptophan, Kuhn says.
“If tryptophan hits our body’s cells, it tends to go get broken down into anti-inflammatory products versus when it hits the bacterial cells and goes more inflammatory. The ways we think about how this could lead to therapies are: How do you keep that balance tipped so that tryptophan goes towards that anti-inflammatory pathway? How can you manipulate intestinal bacteria to tip that balance? That’s where we’re interested in going in the future.”
Does Kuhn’s research suggest we should be eating differently? “I get asked that a lot,” she says. “A diet that’s rich in plant-based fibers and lean meats — this whole Mediterranean diet — seems to push the microbiome into a healthier state, so that you are getting the anti-inflammatory properties of tryptophan, whereas the typical western diet seems to go more toward the inflammatory pathway.”
As for other ways to protect against arthritis, Kuhn says that through research by her Division of Rheumatology colleagues, “we have started to understand the at-risk stage, where we can actually identify people who are likely to progress to rheumatoid arthritis within the next few years based on blood markers. There’s some data that suggests we could intervene during that period and prevent disease, but we’re not quite sure yet what are the right ways to intervene.”

Adults who had amblyopia (‘lazy eye’) in childhood are more likely to experience hypertension, obesity, and metabolic syndrome in adulthood, as well as an increased risk of heart attack, finds a new study led by UCL researchers.
In publishing the study in eClinicalMedicine, the authors stress that while they have identified a correlation, their research does not show a causal relationship between amblyopia and ill health in adulthood.
The researchers analysed data from more than 126,000 participants aged 40 to 69 years old from the UK Biobank cohort, who had undergone ocular examination.
Participants had been asked during recruitment whether they were treated for amblyopia in childhood and whether they still had the condition in adulthood. They were also asked if they had a medical diagnosis of diabetes, high blood pressure, or cardio/cerebrovascular disease (ie. angina, heart attack, stroke).
Meanwhile, their BMI (body mass index), blood glucose, and cholesterol levels were also measured and mortality was tracked.
The researchers confirmed that from 3,238 participants who reported having a ‘lazy eye’ as a child, 82.2% had persistent reduced vision in one eye as an adult.
The findings showed that participants with amblyopia as a child had 29% higher odds of developing diabetes, 25% higher odds of having hypertension and 16% higher odds of having obesity. They were also at increased risk of heart attack — even when other risk factors for these conditions (e.g. other disease, ethnicity and social class) were taken into account.

This increased risk of health problems was found not only among those whose vision problems persisted, but also to some extent in participants who had had amblyopia as a child and 20/20 vision as an adult, although the correlation was not as strong.
Corresponding author, Professor Jugnoo Rahi (UCL Great Ormond Street Institute for Child Health, UCL Institute of Ophthalmology and Great Ormond Street Hospital), said: “Amblyopia is an eye condition affecting up to four in 100 children. In the UK, all children are supposed to have vision screening before the age of five, to ensure a prompt diagnosis and relevant ophthalmic treatment.
“It is rare to have a ‘marker’ in childhood that is associated with increased risk of serious disease in adult life, and also one that is measured and known for every child — because of population screening.
“The large numbers of affected children and their families, may want to think of our findings as an extra incentive for trying to achieve healthy lifestyles from childhood.”
Amblyopia is when the vision in one eye does not develop properly and can be triggered by a squint or being long-sighted.
It is a neurodevelopmental condition that develops when there’s a breakdown in how the brain and the eye work together and the brain can’t process properly the visual signal from the affected eye. As it usually causes reduced vision in one eye only, many children don’t notice anything wrong with their sight and are only diagnosed through the vision test done at four to five years of age.

A recent report from the Academy of Medical Sciences* involving some researchers from the UCL Great Ormond Street Institute for Child Health, called on policymakers to address the declining physical and mental health of children under five in the UK and prioritise child health.
The team hope that their new research will help reinforce this message and highlight how child health lays the foundations for adult health.
First author, Dr Siegfried Wagner (UCL Institute of Ophthalmology and Moorfields Eye Hospital), said: “Vision and the eyes are sentinels for overall health — whether heart disease or metabolic disfunction, they are intimately linked with other organ systems. This is one of the reasons why we screen for good vision in both eyes.
“We emphasise that our research does not show a causal relationship between amblyopia and ill health in adulthood. Our research means that the ‘average’ adult who had amblyopia as a child is more likely to develop these disorders than the ‘average’ adult who did not have amblyopia. The findings don’t mean that every child with amblyopia will inevitably develop cardiometabolic disorders in adult life.”
The research was carried out in collaboration with the University of the Aegean, University of Leicester, King’s College London, the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC) at Moorfields Eye Hospital and UCL Institute of Ophthalmology and the NIHR BRC at UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital.
The work was funded by the Medical Research Council, the NIHR and the Ulverscroft Foundation.

Published32 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Nick TriggleHealth correspondentPatients in parts of England are facing an uphill struggle to see a GP, experts say, after an analysis showed wide regional variation in doctor numbers. The Nuffield Trust think tank found Kent and Medway had the fewest GPs per person, followed by Bedfordshire, Luton and Milton Keynes. It comes as ministers have struggled to hit the pledge to boost the GP workforce by 6,000 this Parliament.But the government said it had plans in place to tackle shortages.Last year, it published a 15-year workforce plan – the first time such a strategy had been developed.Under-doctored regionsBut Dr Billy Palmer, of the Nuffield Trust, said: “Solely boosting the number of staff nationally in the NHS is not enough alone – the next government should set a clear aim of reducing the uneven distribution of key staffing groups and shortfalls to tackle unfairness in access for patients.”The think-tank report found while the government had met its target to increase the number of nurses by 50,000 this Parliament, the rises had not been felt evenly, with some specialist nurse posts, such as health visitors and learning-disability nurses, seeing numbers shrink.Dr Palmer said minimum numbers of GPs may have to be set for local areas – and better incentives to attract them to those with the fewest.Gloucester – the area with the most GPs per person – had 45% more than the most under-doctored regions.The areas with the fewest GPsKent and Medway: 2,702 patients per GPBedfordshire, Luton and Milton Keynes: 2,573Lincolnshire: 2,572 Lancashire and South Cumbria: 2,520 South East London: 2,488 Figures weighted for health and age of populationProf Kamila Hawthorne, who chairs the Royal College of General Practitioners, said: “Without immediate action to alleviate the pressures on general practice, the future of the profession – and the care we’re able to deliver to patients – is uncertain.” While the recruitment and retention of GPs has proved challenging, the government said there were still 2,800 more now than at the start of the Parliament.And the Department of Health and Social Care said the workforce plan would lead to a rapid expansion of training places. “We are working hard to grow the NHS workforce,” a spokesman added.More on this storyMillions miss out on seven-day GP accessPublished30 July 2018

Published3 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Christine HuiBy Jim Reed, Harriet Agerholm & Alison BenjaminBBC NewsCoroners in England and Wales sent 109 warning letters to the government and health bodies in 2023 highlighting long NHS waits, staff shortages or a lack of NHS resources, the BBC has found.The number of cases identified that were linked to NHS pressures was the highest in the past six years.Prevention of future death reports (PFDs) are sent when a coroner thinks action is needed to protect lives.The government says it “responds to, and learns from, every report”.Coroners are specialist judges in charge of inquests, which investigate the circumstances of deaths that appear to have an unknown, violent or unnatural cause.The BBC combed through hundreds of PFD reports written after inquests to find cases linked to long NHS waits or pressure on the health service.The 109 identified in 2023 compared with 58 in 2019, and 49 in 2018, before the pandemic. The BBC also found 62 cases in 2022, 45 cases in 2021, and 37 in 2020, when it was more likely Covid may have affected the number of inquests held and reports written.’Firefighting’William Gray was fond of maths and wanted to be a doctor when he grew up. He died after a life-threatening asthma attack, aged 10. In October 2020, he was struggling to breathe in the middle of the night. His mother gave him CPR and he was rushed to Southend Hospital by ambulance, only to be discharged four hours later.In the months that followed, his family tried and failed to get the specialist help they needed.Some changes were made to William’s inhaler but, after a consultant appointment, he was “lost to follow-up” at the hospital, his inquest heard. His GP did not prescribe continuing preventative medication to control his condition.At the time of his admission, there was a single nurse working in the children’s asthma and allergy service in south-east Essex, increasing to two nurses in November 2020.Staff had a caseload of 2,000 children and demand was growing, with referrals up 75% between 2018 and 2023.”Nurses were being asked to provide the impossible,” coroner Sonia Hayes said at William’s inquest. Staff were “firefighting” and the service was “ludicrous”.Image source, Family photoOn 29 May 2021, William had another severe asthma attack. This time doctors could not save him and he died in hospital.”It’s been horrendous for us, having to try to adjust to life without him,” said his mother Christine Hui.”I just don’t want any other family to go through what we’ve been through.”After William’s inquest in December 2023, the coroner wrote a strongly worded PFD report to Health Secretary Victoria Atkins and the NHS bodies responsible for his care. The children’s asthma service “remains under-resourced”, William’s death was “avoidable”, and better treatment “would and should” have saved his life, the coroner added.In response, Essex Partnership University NHS Trust said it had recruited three more asthma nurses through a pilot scheme, although it had requested funding for eight.”Since this tragic incident, our specialist community asthma services have been remodelled to enhance the care we provide,” a spokeswoman added.Mid and South Essex NHS Trust, which runs Southend Hospital, also said it had introduced “numerous changes” to improve patient care. Prevention of future deathsAbout 35,000 inquests take place in England and Wales each year. In a fraction of those – about 450 – the coroner writes a PFD, or Regulation 28, report.The BBC analysed 2,600 PFDs – and supporting documentation – sent between 2018 and 2023.The proportion of the total number of PFD reports that referenced an NHS resource issue rose to one in five in 2023, from one in nine in the two years before Covid. Of the 540 reports written last year, 109 were found that highlighted a long wait for NHS treatment, a shortage of medical staff or a lack of NHS resources such as beds or scanners. Of these, 26 involved mental illness or suicide, and 31 involved ambulances and emergency services.Image source, Karen ParksThat included the case of Shaun Parks, 52, who was driven to Doncaster Hospital in December 2022 with chest pains. He arrived at midnight and waited in the A&E department for more than an hour before being seen.”Within seconds of the [ECG] machine being hooked up to him, the nurse ripped off a piece of paper and ran,” said his wife Karen.”She came back through and said, ‘Mr Parks, you’re having a heart attack, we need to get you through to the resuscitation area right now’.” Shaun was stabilised and told he needed to be moved to a specialist unit in Sheffield, but his inquest heard high demand and insufficient staffing levels meant the ambulance, which should have arrived in 18 minutes, took more than three hours to pick him up from Doncaster.Shaun died in hospital later that morning. In a PFD sent to the Department of Health in December 2023, the coroner raised concerns about the “significant delay” ambulances were facing offloading patients, and noted that Mr Parks had “deteriorated during his time at Doncaster Royal Infirmary”.”If he had got there earlier, granted it might have been the same outcome, but he would have had more of a chance of survival,” said Karen.”I loved Shaun to bits. I loved the ground he walked on. It shouldn’t happen in this day and age.”After his inquest, NHS West Yorkshire Integrated Care Board, which commissions ambulance services in the region, said it had been investing in more staff and vehicles, though it accepted there were “ongoing challenges” with response times.Image source, Karen ParksAs in Shaun’s case, it can take months, or even years, for an inquest to take place. The latest figures, for 2022, show it took 30 weeks on average from the date someone died until the process was complete and a PFD report could be sent.”Reading the reports is heartbreaking, and our thoughts are with the families and loved ones of all those who died,” said Dr Adrian Boyle, the president of the Royal College of Emergency Medicine. “The link between the issues highlighted and the pressures currently being experienced by our urgent and emergency care system is stark. This is also supported by scientific evidence which shows the single leading theme is delay.”‘Into the ether’NHS trusts, government departments and other organisations have a mandatory duty to respond to PFD reports, but any changes recommended by the coroner are not legally enforceable. Deborah Coles, the director of the charity Inquest, told a parliamentary hearing last month there was a danger reports could simply “disappear into the ether”, with the same mistakes repeated in the future.Inquest, and law firms representing bereaved families, are calling for the creation of a new independent body to audit hundreds of reports each year, and make sure recommendations are implemented.In a statement, the Department of Health and Social Care in England said it learnt from every PFD report.”Our £1bn urgent and emergency care plan sets a clear vision for how we are working to cut waiting times,” said a spokesman, alongside a £2.4bn plan to “train, retain and reform” the NHS workforce. An NHS England spokeswoman added: “Despite ongoing pressures from record demand and high bed occupancy, the NHS continues to focus on improving patient flow, ensuring patients are seen by the most appropriate services and minimising delays.”Sixteen of the 109 PFDs linked to NHS pressure in 2023 were written by coroners in Wales. A spokesman for the Welsh government said it had a “clear urgent and emergency care improvement plan in place, supported by an extra £50m over the past two years”.MethodologyThe BBC analysed 2,600 PFD reports written between 2018 and 2023, and published on the Ministry of Justice website.Many reports are complex, with multiple causes of death and “matters of concern” listed. Whether a coroner decides to issue a report, and the level of detail they choose to include, varies.Cases were identified that clearly referred to pressure on the health service, a shortage of medical staff or a lack of NHS resources.Reports that met the criteria were highlighted and reviewed by more than one person on the BBC team.Additional reporting by John Walton, Aidan McNamee and Joe McFadden.More on this storyHospital patient given ‘corridor care’ for 14 hoursPublished1 day agoThe NHS hidden waiting lists terrifying patientsPublished19 February12-hour A&E waits in winter ‘becoming normalised’Published15 February