Drugs that target opioid receptors sometimes have severe side effects. Thousands of people around the world die every day from overdoses involving opioids such as fentanyl. An international team of researchers has taken a closer look at the molecular mechanisms of these active substances. The research, carried out by Dr Matthias Elgeti, a biophysicist at Leipzig University, in collaboration with research groups from the US and China, has now been published in the journal Nature.
Opioid receptors are of great pharmacological interest because opioid substances regulate the perception of pain. “Our findings provide insights into how an opioid receptor can perform different functions. It is able to reduce pain, but also to regulate digestion or breathing,” explains Dr Elgeti, co-first author of the study from the Institute for Drug Discovery at the Faculty of Medicine.
In the current study, the biophysicist collaborated with international scientists, including the research group of Nobel laureate Brian Kobilka from Stanford University. They discovered that superagonists, such as fentanyl, stabilise a state of the receptor that causes particularly effective and long-lasting signal transmission. This means that superagonists are particularly potent and therefore dangerous. In the current study, the researchers used electron spin resonance and single-molecule fluorescence spectroscopy to determine different states of the opioid receptor and the structural effects of different binding partners.
Opioid receptors are members of the large family of G protein-coupled receptors (GPCRs), which control many signalling processes in the body, such as taste and smell, while others bind neurotransmitters and hormones or are activated by light. Understanding the molecular interactions of these receptors with drugs and other signalling proteins is very important for drug development. As all GPCRs are structurally very similar, the researchers hope that their findings on the opioid receptor can be applied to other receptors.
“This study involved isolating the opioid receptors. They are normally found in the body’s cells, interacting with many other proteins and molecules. Further research into the molecular interactions is therefore needed to gain a full understanding of the regulatory mechanisms,” says Dr Elgeti. The new study is an important building block in basic research, with further studies needed to ultimately develop better and safer medicines.

Melanoma is the deadliest form of skin cancer. With global incidence rates rising, new, more effective treatments are necessary to alleviate the health burden of the disease. Important advances in recent years include doctors using genetic tests to look for specific mutations they can target for more personalised, effective treatment.
Around 1 in 2 melanoma patients will have mutations in the BRAF gene. This gene normally makes a protein which helps control cell growth, but mutations can cause the cells to grow and divide uncontrollably instead, happening in many different types of cancer including melanoma.
The discovery of BRAF mutations has led to development of targeted therapies to inhibit its function. One of the standard treatment options for melanoma over the last ten years has been to simultaneously target both BRAF mutations and MEK. These two genes are part of the MAPK signalling pathway, which, in cancer, is rewired for uncontrolled growth. Targeting two different critical points in the same domino chain helps slow or stop cancer growth.
Despite great initial responses to the combined use of the first-generation inhibitors, around 50% of melanoma patients with BRAF mutations will relapse within one year. The cancer acquires resistance to the drugs, finding other ways to reactive the MAPK pathway through mechanisms which remain poorly understood.
“Melanoma drug resistance is a huge clinical problem because it occurs in almost all BRAF-mutated patients under BRAF/MEK inhibitor therapy and there are few or no therapeutic alternatives. There is an urgent need to understand the many different underlying mechanisms and find new strategies to deal with this constantly evolving arms race,” says Dr. Francisco Aya Moreno, a medically-trained oncologist and recent PhD graduate at the Centre for Genomic Regulation (CRG) in Barcelona.
A study published today in the journal Cell Reports has disentangled the mechanisms behind one of the ways cancer cells develop resistance to targeted therapy. The study found that, in response to treatment, melanomas can ‘break’ parts of their BRAF gene, also known as genomic deletions. This helps the tumour create alternative versions of the protein (altBRAFs) which lack regions targeted by BRAF inhibitors, reactivating the MAPK pathway and making the drugs less effective. The finding was consistent across various lab models and patient tumour samples.
The findings are important because altBRAFs were thought to be made through alternative splicing, which is when cells use the same gene to synthesise different proteins. The discovery that genomic deletions, and not splicing, are the cause means a shift away from previous proposals for using drugs that target splicing as a therapeutic strategy.

“For years, we’ve known that some patients produce altBRAFs and these help the cancer resist treatment, but we misunderstood the mechanism behind their creation. Knowing that genomic deletions are the cause opens new avenues for developing therapies that could more effectively help patients with BRAF mutations,” explains ICREA Research Professor Juan Valcarcel, co-author of the study and researcher at the Centre for Genomic Regulation.
Surprisingly, the researchers found evidence of the same genomic deletions in melanomas which hadn’t been treated yet. In other words, melanomas can naturally develop mechanisms that mimic drug resistance, even without exposure to drugs. Identifying and targeting these early resistance mechanisms through profound genetic testing in a clinical setting before treatment begins could improve the efficacy of first-line therapies.
Even more surprisingly, further analyses revealed that genomic deletions might be a more widespread mechanism of oncogenesis and resistance than previously thought. Though uncommon, researchers found evidence of altBRAFs in melanomas with a normal-functioning BRAF gene, as well as in other types of cancer including non-small cell lung cancer, breast cancer, kidney cancer and prostate cancer. The findings could increase the patient population benefiting from targeted treatments which are currently under clinical development.
“There is an emerging class of drugs known as second generation RAF inibitors. Unlike BRAF inhibitors, these drugs have a broad spectrum, and so could potentially inhibit the function of altBRAFs. Clinical trials which are assessing their effectiveness should also expand to include melanoma patients with a normal functioning BRAF gene as well, and possibly to other cancer types which express altBRAFs,” explains Dr. Aya Moreno.
Dr. Aya Moreno is part of the second cohort of the PhD4MD programme, a joint effort by Centre for Genomic Regulation (CRG), the Institute for Research in Biomedicine (IRB Barcelona), the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the Vall d’Hebron Research Institute (VHIR) designed to leverage the medical insight of a doctor to drive research that benefits patients.
“Having the opportunity to approach this research with both a clinician’s perspective and a scientist’s curiosity has been invaluable. It allowed us to uncover not just how melanomas resist treatment but also how this knowledge could lead to more effective therapies for patients. This fusion of clinical insight and scientific investigation is crucial for making real progress in our fight against cancer,” concludes Dr. Aya Moreno.
The study was led by Dr. Aya Moreno and co-supervised by Professor Juan Valcarcel at the Centre for Genomic Regulation and Dr. Ana Arance at IDIBAPS. It was also carried out in collaboration with Nuria López Bigas’ research group at IRB Barcelona. Since completing his PhD at the CRG, Dr. Aya Moreno has returned to the Medical Oncology department in the Hospital Clinic in Barcelona.

Millions in Sackler donations sat dormant, rising in value as the opioid epidemic raged and as other institutions distanced themselves from the makers of a notorious painkiller.The National Academy of Sciences is asking a court to allow it to repurpose about $30 million in donations from the wealthy Sackler family, who controlled the company at the center of the opioid epidemic, and to remove the family name from the endowment funds.The petition filed by the Academy in Superior Court in Washington, D.C., Thursday aims to modify the terms of the donations so the institution can use them for scientific studies, projects and educational activities.The move follows a report in The New York Times last year that examined donations from several Sackler members, including an executive of Purdue Pharma, which produced the painkiller OxyContin that has long been blamed for fueling the opioid crisis that has claimed thousands of lives.“The notoriety of the Sackler name has made it impossible for the Academy to carry out the purposes for which it originally accepted the funds,” Marcia McNutt, president of the National Academy of Sciences, said in a statement released on Thursday.Daniel S. Connolly, a spokesman for the Raymond Sackler family, said it supported the National Academies in “using the funds as they see fit” and would have supported the change.“We would have said yes if we’d been asked, just as we will still say yes despite this unnecessary court filing and false assertions about us,” Mr. Connolly said in a statement.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.

Published25 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Jeremy CulleyBBC NewsJeremy Paxman said Parkinson’s “makes you wish you hadn’t been born” as he delivered a list of recommendations about the disease to Downing Street. The TV presenter, who was diagnosed in 2021, marked World Parkinson’s Day by presenting a “Parky Charter” to No 10.The charter makes five key recommendations including swift access to specialists under the NHS and increased funding to help find a cure. Rishi Sunak said it would “receive the full attention it deserves”.Paxman, who stepped down as host of University Challenge the year after his diagnosis, went to Downing Street on Thursday with fellow members of the Movers and Shakers podcast, which discusses the challenges of living with the disease. In a frank admission, the former Newsnight presenter, 73, said: “[Parkinson’s] may not kill you but it will make you wish you hadn’t been born.”Paxman criticised the government’s response to the disease after delivering a petition with tens of thousands of names, as well as the charter, which makes five key recommendations:swift access to specialists for individuals with Parkinson’s under the NHS the introduction of a Parkinson’s UK pamphlet for enhanced awareness and support the implementation of a Parkinson’s passport granting automatic entitlement to specific benefits improved comprehensive care, including regular consultations with a Parkinson’s nurseincreased government funding for research for a cure for the diseaseThe prime minister praised the charter and said he was “very supportive of the excellent work that the Movers and Shakers do”.But Paxman fears the charter and petition will have “no effect whatsoever” on the government.He told the PA news agency: “The fact they [the government] have ignored all their responsibilities to date indicates to me that they’re not going to get any better.”And I suspect that the form of words devised by the Ministry of Health will confirm that.”I don’t think we’re going to get anywhere. You feel like you’re banging your head against a brick wall.”Image source, PA MediaThe Movers and Shakers podcast began in February 2023 and also features former BBC journalist Rory Cellan-Jones, the broadcaster’s ex-Europe and North America editor Mark Mardell, correspondent Gillian Lacey-Solymar, the late Princess Diana’s divorce barrister Sir Nick Mostyn and Vicar of Dibley co-writer Paul Mayhew-Archer.A Department of Health and Social Care spokesperson said: “We want a society where every person with a neurological disease, along with their families and carers, receives high-quality, compassionate care – and having a better understanding of diseases like Parkinson’s is vital in making sure we can provide the right care at the right time.”That’s why we committed to spend at least £375m in research into neurodegenerative diseases over five years, so that we can better understand these conditions and improve outcomes for patients.”What is Parkinson’s disease?Parkinson’s UK describes it as the fastest growing neurological condition in the world and currently there is no cure. It says anyone can get Parkinson’s, young or old, and in the UK roughly 153,000 people are living with the condition, with two more people diagnosed every hour. The three main symptoms are involuntary shaking, slow movement and stiff and inflexible muscles, but sufferers can experience a wide range of other problems, including depression and anxiety.More on this storyPaxman steps down from University ChallengePublished16 August 2022Jeremy Paxman receiving treatment for Parkinson’sPublished21 May 2021New Parkinson’s drug to be rolled out on NHSPublished16 February

Mother Nature is an artist, but her craft of creating animal faces requires more than a paintbrush and palette. Such highly complex shapes originate from their respective transient neural crest cells.
These embryonic pluripotent cells within the facial primordium — the early development form — may be necessary for forming proper facial structures. However, analyzing the molecular mechanisms in such early stages of development poses many technical challenges.
Now, a group of Kyoto University researchers have produced neural crest cell-rich aggregates from human pluripotent stem cells and developed a method to differentiate them in cell populations with a branchial arch-like gene expression pattern.
“After the cell populations differentiate into precursors of maxillary and mandibular cells in response to external signalling factors, these populations spontaneously form patterns of the facial primordium,” explains Yusuke Seto of KyotoU’s Institute for Medical and Biological Research.
This cartilage-like structure, reminiscent of Meckel’s cartilage, is formed locally within the aggregates.
“We aim to establish a model for studying early facial development by using the properties of human pluripotent stem cells to generate in vitro tissue resembling the bronchial arch of the primordial face,” adds Ryoma Ogihara, also of the Institute.
Researchers are examining the various developmental processes that cause interspecific and individual differences in facial structure to explain conditions such as craniofacial disorders.
“Using our in vitro model could help us better understand and control signal integration during the fate determination of the branchial arch and cartilage formation in the face and elsewhere. We hope our technology can contribute to the development of cellular materials for new regenerative medicine,” adds Mototsugu Eiraku, also of the Institute.

Inside the brains of people with psychosis, two key systems are malfunctioning: a “filter” that directs attention toward important external events and internal thoughts, and a “predictor” composed of pathways that anticipate rewards.
Dysfunction of these systems makes it difficult to know what’s real, manifesting as hallucinations and delusions.
The findings come from a Stanford Medicine-led study, publishing April 11 in Molecular Psychiatry, that used brain scan data from children, teens and young adults with psychosis. The results confirm an existing theory of how breaks with reality occur.
“This work provides a good model for understanding the development and progression of schizophrenia, which is a challenging problem,” said lead author Kaustubh Supekar, PhD, clinical associate professor of psychiatry and behavioral sciences.
The findings, observed in individuals with a rare genetic disease called 22q11.2 deletion syndrome who experience psychosis as well as in those with psychosis of unknown origin, advance scientists’ understanding of the underlying brain mechanisms and theoretical frameworks related to psychosis.
During psychosis, patients experience hallucinations, such as hearing voices, and hold delusional beliefs, such as thinking that people who are not real exist. Psychosis can occur on its own and is a hallmark of certain serious mental illnesses, including bipolar disorder and schizophrenia. Schizophrenia is also characterized by social withdrawal, disorganized thinking and speech, and a reduction in energy and motivation.
It is challenging to study how schizophrenia begins in the brain. The condition usually emerges in teens or young adults, most of whom soon begin taking antipsychotic medications to ease their symptoms. When researchers analyze brain scans from people with established schizophrenia, they cannot distinguish the effects of the disease from the effects of the medications. They also do not know how schizophrenia changes the brain as the disease progresses.

To get an early view of the disease process, the Stanford Medicine team studied young people aged 6 to 39 with 22q11.2 deletion syndrome, a genetic condition with a 30% risk for psychosis, schizophrenia or both.
Brain function in 22q11.2 patients who have psychosis is similar to that in people with psychosis of unknown origin, they found. And these brain patterns matched what the researchers had previously theorized was generating psychosis symptoms.
“The brain patterns we identified support our theoretical models of how cognitive control systems malfunction in psychosis,” said senior study author Vinod Menon, PhD, the Rachael L. and Walter F. Nichols, MD, Professor; a professor of psychiatry and behavioral sciences; and director of the Stanford Cognitive and Systems Neuroscience Laboratory.
Thoughts that are not linked to reality can capture the brain’s cognitive control networks, he said. “This process derails the normal functioning of cognitive control, allowing intrusive thoughts to dominate, culminating in symptoms we recognize as psychosis.”
Cerebral sorting
Normally, the brain’s cognitive filtering system — aka the salience network — works behind the scenes to selectively direct our attention to important internal thoughts and external events. With its help, we can dismiss irrational thoughts and unimportant events and focus on what’s real and meaningful to us, such as paying attention to traffic so we avoid a collision.

The ventral striatum, a small brain region, and associated brain pathways driven by dopamine, play an important role in predicting what will be rewarding or important.
For the study, the researchers assembled as much functional MRI brain-scan data as possible from young people with 22q11.2 deletion syndrome, totaling 101 individuals scanned at three different universities. (The study also included brain scans from several comparison groups without 22q11.2 deletion syndrome: 120 people with early idiopathic psychosis, 101 people with autism, 123 with attention deficit/hyperactivity disorder and 411 healthy controls.)
The genetic condition, characterized by deletion of part of the 22nd chromosome, affects 1 in every 2,000 to 4,000 people. In addition to the 30% risk of schizophrenia or psychosis, people with the syndrome can also have autism or attention deficit hyperactivity disorder, which is why these conditions were included in the comparison groups.
The researchers used a type of machine learning algorithm called a spatiotemporal deep neural network to characterize patterns of brain function in all patients with 22q11.2 deletion syndrome compared with healthy subjects. With a cohort of patients whose brains were scanned at the University of California, Los Angeles, they developed an algorithmic model that distinguished brain scans from people with 22q11.2 deletion syndrome versus those without it. The model predicted the syndrome with greater than 94% accuracy. They validated the model in additional groups of people with or without the genetic syndrome who had received brain scans at UC Davis and Pontificia Universidad Católica de Chile, showing that in these independent groups, the model sorted brain scans with 84% to 90% accuracy.
The researchers then used the model to investigate which brain features play the biggest role in psychosis. Prior studies of psychosis had not given consistent results, likely because their sample sizes were too small.
Comparing brain scans from 22q11.2 deletion syndrome patients who had and did not have psychosis, the researchers showed that the brain areas contributing most to psychosis are the anterior insula (a key part of the salience network or “filter”) and the ventral striatum (the “reward predictor”); this was true for different cohorts of patients.
In comparing the brain features of people with 22q11.2 deletion syndrome and psychosis against people with psychosis of unknown origin, the model found significant overlap, indicating that these brain features are characteristic of psychosis in general.
A second mathematical model, trained to distinguish all subjects with 22q11.2 deletion syndrome and psychosis from those who have the genetic syndrome but without psychosis, selected brain scans from people with idiopathic psychosis with 77.5% accuracy, again supporting the idea that the brain’s filtering and predicting centers are key to psychosis.
Furthermore, this model was specific to psychosis: It could not classify people with idiopathic autism or ADHD.
“It was quite exciting to trace our steps back to our initial question — ‘What are the dysfunctional brain systems in schizophrenia?’ — and to discover similar patterns in this context,” Menon said. “At the neural level, the characteristics differentiating individuals with psychosis in 22q11.2 deletion syndrome are mirroring the pathways we’ve pinpointed in schizophrenia. This parallel reinforces our understanding of psychosis as a condition with identifiable and consistent brain signatures.” However, these brain signatures were not seen in people with the genetic syndrome but no psychosis, holding clues to future directions for research, he added.
Applications for treatment or prevention
In addition to supporting the scientists’ theory about how psychosis occurs, the findings have implications for understanding the condition — and possibly preventing it.
“One of my goals is to prevent or delay development of schizophrenia,” Supekar said. The fact that the new findings are consistent with the team’s prior research on which brain centers contribute most to schizophrenia in adults suggests there may be a way to prevent it, he said. “In schizophrenia, by the time of diagnosis, a lot of damage has already occurred in the brain, and it can be very difficult to change the course of the disease.”
“What we saw is that, early on, functional interactions among brain regions within the same brain systems are abnormal,” he added. “The abnormalities do not start when you are in your 20s; they are evident even when you are 7 or 8.”
The researchers plan to use existing treatments, such as transcranial magnetic stimulation or focused ultrasound, targeted at these brain centers in young people at risk of psychosis, such as those with 22q11.2 deletion syndrome or with two parents who have schizophrenia, to see if they prevent or delay the onset of the condition or lessen symptoms once they appear.
The results also suggest that using functional MRI to monitor brain activity at the key centers could help scientists investigate how existing antipsychotic medications are working.
Although it’s still puzzling why someone becomes untethered from reality — given how risky it seems for one’s well-being — the “how” is now understandable, Supekar said. “From a mechanistic point of view, it makes sense,” he said.
“Our discoveries underscore the importance of approaching people with psychosis with compassion,” Menon said, adding that his team hopes their work not only advances scientific understanding but also inspires a cultural shift toward empathy and support for those experiencing psychosis.
“I recently had the privilege of engaging with individuals from our department’s early psychosis treatment group,” he said. “Their message was a clear and powerful: ‘We share more similarities than differences. Like anyone, we experience our own highs and lows.’ Their words were a heartfelt appeal for greater empathy and understanding toward those living with this condition. It was a call to view psychosis through a lens of empathy and solidarity.”
Researchers contributed to the study from UCLA, Clinica Alemana Universidad del Desarrollo, Pontificia Universidad Católica de Chile, the University of Oxford and UC Davis.
The study was funded by the Stanford Maternal and Child Health Research Institute’s Uytengsu-Hamilton 22q11 Neuropsychiatry Research Program, FONDEYCT (the National Fund for Scientific and Technological Development of the government of Chile), ANID-Chile (the Chilean National Agency for Research and Development) and the U.S. National Institutes of Health (grants AG072114, MH121069, MH085953 and MH101779).

Published24 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Michelle RobertsDigital health editorFrom Monday, the NHS will take bookings from people in England wanting a free spring Covid booster vaccine. Those eligible, including everyone aged 75 or older or with a weak immune system, can book via the NHS website, app or by calling 119.Covid is now a relatively mild disease for the vast majority but can still be very dangerous and even life-threatening for some. Vaccines lower the risk but protection fades, so top-up jabs are offered. Who can have a free booster job?Those eligible for a top-up shot at pharmacies and GP practices include:everyone aged 75 or older by 30 June 2024people in care homes for older adultsanyone immunosuppressed who is aged six months or olderSome walk-in centres are also offering it.The NHS is sending texts, emails, app messages or letters to those eligible – but they do not need to wait for the invitation to book.Covid booster: Who can get another jab?Covid vaccines: safety and side effectsCovid inquiry postpones vaccine investigationUK Health Security Agency immunisations director Dr Mary Ramsay said: “With Covid-19 still circulating, it’s important those at highest risk who are eligible for the spring vaccine get their jab to help top up their immunity.”We are still seeing Covid-19 causing hospitalisations and severe illness, particularly among older people and those with weakened immune systems.”And the vaccine provides the best protection – so don’t put it off.”If you’re eligible, book your appointment as soon as you’re invited by the NHS.”Which Covid vaccine is being used?Several different vaccines are in use in the UK. The boosters are Pfizer-BioNTech or Moderna messenger ribonucleic acid (mRNA) vaccines updated against more recent Covid variants. Can people buy a Covid booster? Some high street chemists and private clinics have started selling and administering Covid vaccines to people aged 12 and over, for about £45-£99. A health professional speaks to each customer to check the booster is suitable. The BBC spoke with Pharmadoctor, which assists the bookings with some pharmacies that offer the service.Chief executive Graham Thomas told BBC News there had been big demand in the few weeks since the Pfizer vaccine went on sale, with more than 1,500 customers buying it at pharmacies his company works with. Of them, 84% had no underlying medical conditions.Many of the rest had conditions such as chronic lung or heart disease. And 45 classed themselves as carers, looking after someone vulnerable. A protein-based booster vaccine made by Novavax, which works in a more traditional way than the mRNA ones, should also be available to buy soon. Moderna hopes to launch a combined flu and Covid vaccine in 2025.More on this storyCovid jab could be available privately from 2024Published5 October 2023German patient vaccinated against Covid 217 timesPublished5 MarchCovid jab skipped by 44%, entire UK study findsPublished16 January

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Jemma Crew & Tim JohnsBBC NewsUnpaid carers who have been told to repay thousands of pounds of benefits after accidentally earning too much money years ago say it is wrong and unfair. Two former Department for Work and Pensions (DWP) ministers have told the BBC they are calling for the government to pause its demands for repayments of large sums of money.Gina Price had been looking after her dad for a decade before she realised she could apply for Carer’s Allowance in 2013. By this time she was working part-time at a petrol station as well as caring for her father, who had a series of conditions including a hip replacement that did not go to plan. She says she received Carer’s Allowance for about five years. She says she would sometimes agree to work an extra shift, but would do fewer other weeks. This way, she believed she would remain under the earnings threshold to qualify for the benefit.But in 2019, she received a letter saying she owed the DWP about £7,600, to cover overpayments for periods over three-and-a-half years to February 2018. DWP take woman’s inheritance over supermarket job The 59-year-old says she was “astounded” by the amount, and has been repaying £100 a month since. “It’s always grieved me,” she says. “I think it’s so unfair.” Ms Price is one of dozens of listeners who shared their stories with the BBC after the issue was covered on Radio 2’s Jeremy Vine show.Full-time carers can claim £81.90 a week, but they become ineligible for the whole amount if they earn just a pound over £151 a week, after tax and expenses. Carers told the BBC they were unaware they had exceeded the threshold until being informed years later, when the sums had run into the thousands.Image source, Gina PriceMs Price, from Carmarthenshire in south-west Wales, says: “I’m sorry to my heart I ever [claimed it], because it was an absolute nightmare amount to owe.”It added to her grief after her father died in 2019, she says, describing the debt as a “big, big weight on me on top of everything else”.”I was so browbeaten after everything with my father, he was dying by the time they’d approached me, and I just wanted to pay them, keep them off my back, and I needed to get on with my life,” she said.The DWP has faced criticism for failing to prevent overpayments, despite having the ability to do so, and allowing some recipients to end up in legal trouble.Benefit staff get automatic alerts from HM Revenue and Customs (HMRC) if a Carer’s Allowance claimant is earning too much.Claimants have a responsibility to ensure they are entitled to benefits they claim, the DWP says.Five years ago, the House of Commons Work and Pensions Committee accused the DWP of “bullying and harassing” those who had been overpaid.In a report it published in 2019, it also said problems with the DWP’s systems, and staff shortages, had led to “substantial backlogs” in checking flagged cases of potential overpayments.Carers bullied by government, MPs say As of February 2023, the DWP said it was seeking to recover 145,567 overpayments of Carer’s Allowance, which is given to people who provide at least 35 hours a week of care. That includes almost 12,000 cases concerning overpayments of between £5,001 and £20,000.’I was so shocked, I could have fallen through the floor’Andrea Hawley, from Battle in East Sussex, believes she will be repaying money for the next decade. The 50-year-old left her job in 2009 to care for her son, who has a genetic disorder, autism, a learning delay, and skeletal and heart problems. She started working part-time in her family business for about two hours a day, while claiming Carer’s Allowance.In 2019, Mrs Hawley says she received a letter telling her she owed the DWP just over £14,000 – later reduced to about £12,700 – in overpayments made between May 2013 and December 2017.”I can remember being so shocked I could have fallen through the floor,” she told BBC News.The DWP arranged to deduct £80 a month from her Carer’s Allowance to cover the overpayments. Mrs Hawley says she stopped receiving the benefit in 2022, and now pays £50 monthly from her wages. She says she did not realise she was above the earnings threshold, adding: “It’s just so wrong. Why don’t they let you know sooner? “Why do they let it go for years and years and years, and then say ‘you owe us all this money’?”.’Penalised for being honest’Cristina Odone, head of the family policy unit at the Centre for Social Justice, told the BBC the “so-called debts should be forgiven”.She added: “One of the causes for this scandalous miscarriage of justice is that the DWP’s own IT system was able to flag when the earnings threshold was breached, but they failed to alert the carers themselves that they were now in a perilous situation and could end up owing thousands of pounds.”Lesley Whitehouse, 53, from Coventry, spent years as the primary carer for her sister who has severe mental and physical disabilities.A social worker told her she was eligible for Carer’s Allowance and helped her fill in the forms. She started a part-time job in a pub and sent a P60 to the DWP every year.About four years ago, she moved to a full-time position to support her two children.Image source, Dave Hearn”I rang the DWP and told them to stop the carer’s allowance,” she said.”They asked me some questions. Then they came back and told me I shouldn’t have been receiving it and sent me a bill of £18,000.”I just broke down in tears. I said ‘what do you mean?’ I didn’t understand because they’d had my P60 each year. I felt like I was being penalised for being honest.”I wasn’t even earning enough to support my family. I didn’t have any savings. I was living month to month.”She says she has taken on extra hours to repay £50 a month, adding: “I’ll be paying it off for the rest of my life. I wish I’d never claimed it in the first place”.’Scandalous miscarriage of justice’Former Conservative Work and Pensions Secretary Sir Iain Duncan Smith is calling for the government to review what has been going on with large overpayments. The ex-Tory party leader said: “The best thing is for the DWP now to pause any of these demands, review carefully what was behind all of this to make sure this was not mistakes by DWP but is genuinely about individuals failing to notify the department.”Sir Steve Webb, a Liberal Democrat pensions minister in the coalition government who now works at a pensions consultancy, agrees a pause is “probably the right answer”.”But simply saying ‘we won’t reclaim any overpayments’ is too difficult. You can’t readily draw a line in law between the inadvertent and deliberate overclaiming of payments,” he told the BBC. Sir Steve also says the earnings limit should be scrapped, telling the Jeremy Vine show: “These are people who are absolutely at their wits’ end and to then come along and say ‘oh, you went a pound or two over the limit, you know, here’s a court case or a fine’ or whatever. It’s just outrageous.”Carers UK chief executive Helen Walker told the BBC: “We are calling for a clear threshold for debt incurred – a maximum limit which triggers an examination to address cases of overpayment promptly, avoiding further financial difficulties and heartache for families. “Any overpayments over six weeks should be written off.”A DWP spokesperson said: “We are committed to fairness in the welfare system, with safeguards in place for managing repayments while protecting the public purse.”Claimants have a responsibility to inform DWP of any changes in their circumstances that could impact their award, and it is right that we recover taxpayers’ money when this has not occurred.”Are you affected by the issues raised in this story? Share your experiences by emailing haveyoursay@bbc.co.uk.Please include a contact number if you are willing to speak to a BBC journalist. You can also get in touch in the following ways:WhatsApp: +44 7756 165803Tweet: @BBC_HaveYourSayUpload pictures or videoPlease read our terms & conditions and privacy policy

If you are reading this page and can’t see the form you will need to visit the mobile version of the BBC website to submit your question or comment or you can email us at HaveYourSay@bbc.co.uk. Please include your name, age and location with any submission. More on this storyDWP take woman’s inheritance over supermarket jobPublished4 AprilCarers bullied by government, MPs sayPublished2 August 2019

We want to hear from doctors, nurses, technicians, patients and others with experience in the system. Tell us your experiences below.The New York Times is interested in the organ transplant system.Do you have a tip about irregularities in the system? If so, we need your help.If you are a doctor, nurse, technician or anybody else working on organ transplants, we’d love to hear from you. We are also eager to talk to from medical residents working in those transplant programs. And of course, we also want to hear from patients and their families.Share your story about the organ transplant systemWe will not publish any part of your submission without contacting you first. We may use your contact information to follow up with you.

A Houston hospital is investigating whether a doctor altered a transplant list to make his patients ineligible for care. A disproportionate number of them have died while waiting for new organs.For decades, Dr. J. Steve Bynon Jr., a transplant surgeon in Texas, gained accolades and national prominence for his work, including by helping to enforce professional standards in the country’s sprawling organ transplant system.But officials are now investigating allegations that Dr. Bynon was secretly manipulating a government database to make some of his own patients ineligible to receive new livers, potentially depriving them of lifesaving care.Memorial Hermann-Texas Medical Center in Houston, where Dr. Bynon oversaw both the liver and kidney transplant programs, abruptly shut down those programs in the past week while looking into the allegations.On Thursday, the medical center, a teaching hospital affiliated with the University of Texas, said in a statement that it had found evidence that a doctor in its liver transplant program had effectively denied patients transplants by changing records. Officials identified the physician as Dr. Bynon, who is employed by the University of Texas Health Science Center at Houston and has had a contract to lead Memorial Hermann’s abdominal transplant program since 2011.It was not clear what could have motivated Dr. Bynon to possibly tamper with the records. Reached by phone on Thursday, he referred questions to UTHealth Houston, which declined to comment.Founded in 1925, Memorial Hermann is a major hospital in Houston, but it has a relatively small liver transplant program. Last year, it performed 29 liver transplants, according to federal data, making it one of the smallest programs in Texas.Share your story about the U.S. organ transplant systemWe will not publish any part of your submission without contacting you first. We may use your contact information to follow up with you.