DNA discovery highlights how we maintain healthy blood sugar levels after meals
The findings, published today in Nature Genetics, could help inform future treatments of type 2 diabetes, which affects around 4 million people in the UK and over 460 million people worldwide.
Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.
A key player in the development of the condition is insulin, a hormone that regulates blood sugar – glucose – levels. People who have type 2 diabetes are unable to correctly regulate their glucose levels, either because they don’t secrete enough insulin when glucose levels increase, for example after eating a meal, or because their cells are less sensitive to insulin, a phenomenon known as ‘insulin resistance’.
Most studies to date of insulin resistance have focused on the fasting state – that is, several hours after a meal – when insulin is largely acting on the liver. But we spend most of our time in the fed state, when insulin acts on our muscle and fat tissues.
It’s thought that the molecular mechanisms underlying insulin resistance after a so-called ‘glucose challenge’ – a sugary drink, or a meal, for example – play a key role in the development of type 2 diabetes. Yet these mechanisms are poorly-understood.
Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, said: “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population, and whether it’s relevant to the risk of getting type 2 diabetes.”
To examine these mechanisms, an international team of scientists used genetic data from 28 studies, encompassing more than 55,000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.
The team identified new 10 loci – regions of the genome – associated with insulin resistance after the sugary drink. Eight of these regions were also shared with a higher risk of type 2 diabetes, highlighting their importance.
One of these newly-identified loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. This locus was associated with a reduced amount of GLUT4 in muscle tissue.
To look for additional genes that may play a role in glucose regulation, the researchers turned to cell lines taken from mice to study specific genes in and around these loci. This led to the discovery of 14 genes that played a significant role in GLUT 4 trafficking and glucose uptake – with nine of these never previously linked to insulin regulation.
Further experiments showed that these genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. The less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood.
Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: “What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes.”
Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.
Professor Claudia Langenberg, Director of the Precision Healthcare University Research Institute (PHURI) at Queen Mary University of London and Professor of Computational Medicine at the Berlin Institute of Health, Germany, said: “Our findings open up a potential new avenue for the development of treatments to stop the development of type 2 diabetes. It also shows how genetic studies of dynamic challenge tests can provide important insights that would otherwise remain hidden.”
The research was supported by Wellcome, the Medical Research Council and the National Institute for Health and Care Research.
Reference
Williamson, A et al. Genome-wide association study and functional characterisation identifies candidate genes for insulin-stimulated glucose uptake. Nat Gen; 8 June 2023; DOI: 10.1038/s41588-023-01408-9
A study of the DNA of more than 55,000 people worldwide has shed light on how we maintain healthy blood sugar levels after we have eaten, with implications for our understanding of how the process goes wrong in type 2 diabetes.
type 2 diabetesinsulinGenomicsPublic healthSteve O'RahillyAlice WilliamsonWellcomeMedical Research CouncilNational Institute for Health Research (NIHR)School of Clinical MedicineWellcome-MRC Institute of Metabolic ScienceMetabolic Research LaboratoriesMedical Research Council (MRC) Epidemiology UnitCambridge Public HealthSchool of the Physical SciencesWhat’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies workAlice Williamsoneak_kkk (Pixabay)Cola
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Outstanding Cambridge biomedical and health researchers elected to Academy of Medical Sciences Fellowship 2023
The new Fellows have been elected to the Academy in recognition of their exceptional contributions to the advancement of biomedical and health science, cutting-edge research discoveries and translating developments into benefits for patients and wider society.
They join a prestigious Fellowship of 1,400 esteemed researchers who are central to the Academy’s work. This includes providing career support to the next generation of researchers and contributing to the Academy’s influential policy work to improve health in the UK and globally.
Professor Dame Anne Johnson PMedSci, President of the Academy of Medical Sciences, said: “These new Fellows are pioneering biomedical research and driving life-saving improvements in healthcare. It’s a pleasure to recognise and celebrate their exceptional talent by welcoming them to the Fellowship.
“This year, we are celebrating our 25th anniversary. The Fellowship is our greatest asset, and their broad expertise and dynamic ability has shaped the Academy to become the influential, expert voice of health. As we look to the future, the collective wisdom our new Fellows bring will be pivotal in achieving our mission to create an open and progressive research sector to improve the health of people everywhere.”
The new Cambridge Fellows are:
Professor Charlotte Coles FMedSci
Professor of Breast Cancer Clinical Oncology, Department of Oncology, NIHR Research Professor and Director of Cancer Research UK RadNet Cambridge
Professor Coles leads practice-changing breast radiotherapy trials, has influenced international hypofractionation policy and is addressing global health, gender and equity challenges within the Lancet Breast Cancer Commission.
“It’s an honour to be elected as a new Fellow of the Academy of Medical Sciences. This is a result of research collaborations in Cambridge, the UK and internationally and I’d like to thank these wonderful colleagues, especially patient advocates,” said Coles.
“I hope to contribute to the Academy’s work to increase equity, diversity and inclusion within leadership roles, including lower- and middle-income countries, to enrich research and improve the culture in Medical Sciences.”
Professor Emanuele Di Angelantonio FMedSci
Professor of Clinical Epidemiology and Donor Health, Department of Public Health and Primary Care, and Head of Health Data Science Centre, Human Technopole (Milan)
Professor Di Angelantonio’s research has focused on addressing major clinical and public health priorities in cardiovascular disease (CVD) and transfusion medicine. His election recognises his many contributions both in helping resolve important controversies in CVD prevention strategies and in improving the safety and efficiency of blood donation.
“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences, which I recognise is an outcome of the collaborations with many colleagues in UK and worldwide,” said Di Angelantonio.
“Research excellence across medical sciences and translation to health improvements has been at the centre of the Academy’s mission and I am very pleased to now be able to contribute to fulfilling this aim as a Fellow.”
Dr Rita Horvath FMedSci
Director of Research in Genetics of Rare Neurological Disorders in the Department of Clinical Neurosciences and Honorary Consultant in Neurology
Dr Horvath is an academic neurologist using genomics and biochemistry to diagnose rare, inherited neurological disorders, with a focus on mitochondrial diseases. Throughout her career she has combined fundamental experimental work with clinical studies. She pioneered the development and implementation of next generation sequencing in the diagnosis of rare neurogenetic diseases in the UK, leading to precision genetic approaches. She has established extensive international collaborations, having impact in Europe, but also for underserved groups in countries where such expertise is lacking.
“I am delighted and honoured to be elected to this Fellowship, which recognises the impact of my work. I would not have achieved it without the support of my excellent colleagues and research team, for which I give my sincere thanks,” said Horvath.
“As a Hungarian woman working in different countries before I arrived in the UK in 2007, I feel particularly proud of this award, which I recognise is an outcome of the open and fair research environment in Cambridge. This Fellowship enables me to further expand my research to develop effective treatments for patients with rare inherited neurological diseases.”
Professor Eric Miska FMedSci
Herchel Smith Chair of Molecular Genetics and Head of Department of Biochemistry, Affiliated Senior Group Leader at the Gurdon Institute, Associate Faculty at the Wellcome Sanger Institute and Fellow of St John’s College
Professor Miska is a molecular geneticist who has carried out pioneering work on RNA biology. His work led to fundamentally new insights into how small RNA molecules control our genes and protect organisms from selfish genes and viruses, and how RNA can carry heritable information across generations. Miska is Founder and Director of STORM Therapeutics Ltd, which creates novel therapies that inhibit RNA modifying enzymes for use in oncology and other diseases.
“Wonderful recognition of the work of an amazing team of researchers I have the pleasure to work with,” said Miska. “Most of our research has been done using the roundworm C. elegans. As Friedrich Nietzsche wrote in Thus Spoke Zarathustra: ‘You have evolved from worm to man, but much within you is still worm’.”
Professor Serena Nik-Zainal FMedSci
NIHR Research Professor, Professor of Genomic Medicine and Bioinformatics, Department of Medical Genetics and Early Cancer Institute, and Honorary Fellow of Murray Edwards College
Professor Nik-Zainal’s research is focused on investigating the vast number of mutations that occur in human DNA from birth, causing patterns called ‘mutational signatures’, and the associated physiological changes to cellular function, in progressive diseases such as cancer and neurodegeneration. She uses a combination of experimental and computational methods to understand biology and to develop clinical tests for early detection and precision diagnostics. Her team also builds computational tools to enable genomic advances become more accessible across the NHS.
“What an honour it is to be elected to the Fellowship. This is a wonderful recognition of the work from my team,” said Nik-Zainal. “We are thrilled and hugely indebted to all our inspiring collaborators, supporters and patients, who have shared in our passion and joined us on our path, exploring biomedical science and translating insights into patient benefit.”
Professor Julian Rayner FMedSci
Director of the Cambridge Institute for Medical Research, School of Clinical Medicine, Honorary Faculty at the Wellcome Sanger Institute, and Director of Wellcome Connecting Science
Professor Rayner’s research has made significant contributions to our understanding of how malaria parasites recognise and invade human red blood cells to cause disease. His work has helped to identify new vaccine targets, such as a protein essential for red blood cell invasion that is now in early stage human vaccine testing, and inform antimalarial drug development, through co-leading the first ever genome-scale functional screens in malaria parasites. He collaborates closely with researchers in malaria-endemic countries and is strongly committed to engaging public audiences with the process and outcomes of science.
“Malaria is a devastating and too often forgotten disease that still kills more than half a million children every year. Tackling it requires deep collaboration and working across disciplines. I’m enormously honoured by this announcement, which reflects not my work but the work of all the talented people I’ve been lucky enough to host in my lab, and collaborations with friends and colleagues across the world,” said Rayner.
“I’m excited to become a Fellow of the Academy of Medical Sciences because I strongly share their conviction that science is not just for scientists. I believe that dialogue, learning and public engagement are all fundamental and essential parts of the research process, and I look forward to contributing to their leading role in these areas.”
Professor James Rowe FMedSci
Professor of Cognitive Neurology, Department of Clinical Neurosciences, and MRC Cognition and Brain Sciences Unit
Professor Rowe leads a highly interdisciplinary research team at the Cambridge Centre for Frontotemporal Dementia and at Dementias Platform UK to improve the diagnosis and treatment of people affected by dementia. His work integrates cognitive neuroscience, brain imaging, fluidic biomarkers, computational models and neuropathology for experimental medicine studies and clinical trials. He is motivated by his busy clinical practice and the need for better diversity and inclusivity throughout medical research.
“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences. It is a testament to the many wonderful colleagues and students I have been fortunate to work with, and to inspirational mentors,” said Rowe.
“Research excellence, and translation of research for direct human benefit, comes from innovation and collaboration in diverse cross-disciplinary teams. I believe in the vision and values of the Academy as the route to better health for all.”
In addition, two researchers from the wider community have also been elected:
Dr Trevor Lawley FMedSci, Senior Group Leader, Wellcome Sanger Institute and Chief Scientific Officer, Microbiotica
Professor Ben Lehner FRS FMedSci, Senior Group Leader, Human Genetics Programme, Wellcome Sanger Institute
Seven Cambridge University researchers are among the 59 biomedical and health researchers elected to the Academy of Medical Sciences Fellowship.
fellowshiphealthbiomedicalCharlotte ColesEmanuele Di AngelantonioRita HorvathEric MiskaSerena Nik-ZainalJulian RaynerJames RoweThe Academy of Medical SciencesWellcome Sanger InstituteDepartment of OncologyDepartment of Public Health and Primary CareDepartment Clinical NeurosciencesDepartment of BiochemistryGurdon InstituteDepartment of Medical GeneticsCambridge Institute for Medical Research (CIMR)MRC Cognition and Brain Sciences UnitSchool of Clinical MedicineSchool of Biological SciencesSt John's CollegeMurray Edwards CollegeSchool of the Biological SciencesAs we look to the future, the collective wisdom our new Fellows bring will be pivotal in achieving our mission to create an open and progressive research sector to improve the health of people everywhereProfessor Dame Anne Johnson, President of the Academy of Medical SciencesClockwise from top left: E. Di Angelantonio, J. Rayner, J. Rowe, R. Horvath, S. Nik-Zainal, E. Miska, C. Coles
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Obesity accelerates loss of COVID-19 vaccination immunity, study finds
Clinical trials have shown that COVID-19 vaccines are highly effective at reducing symptoms, hospitalisation and deaths caused by the virus, including for people with obesity. Previous studies have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear.
This study, published in the journal Nature Medicine, shows that the ability of antibodies to neutralise the virus declines faster in vaccinated people who have obesity. The findings have important implications for vaccine prioritisation policies around the world.
During the pandemic, people with obesity were more likely to be hospitalised, require ventilators and to die from COVID-19. In this study, supported by the NIHR Bioresource and funded by UKRI, the researchers set out to investigate how far two of the most extensively used vaccines protect people with obesity compared to those with a normal weight, over time.
A team from the University of Edinburgh, led by Prof Sir Aziz Sheikh, looked at real-time data tracking the health of 3.5 million people in the Scottish population as part of the EAVE II study. They looked at hospitalisation and mortality from COVID-19 in adults who received two doses of COVID-19 vaccine (either Pfizer-BioNTech BNT162b2 mRNA or AstraZeneca ChAdOx1).
They found that people with severe obesity (a BMI greater than 40 kg/m2) had a 76% higher risk of severe COVID-19 outcomes, compared to those with a normal BMI. A modest increase in risk was also seen in people with obesity (30-39.9kg/m2), which affects a quarter of the UK population, and those who were underweight. ‘Break-through infections’ after the second vaccine dose also led to hospitalisation and death sooner (from 10 weeks) among people with severe obesity, and among people with obesity (after 15 weeks), than among individuals with normal weight (after 20 weeks).
Prof Sir Aziz Sheikh said: “Our findings demonstrate that protection gained through COVID-19 vaccination drops off faster for people with severe obesity than those with a normal body mass index. Using large-scale data assets such as the EAVE II Platform in Scotland have enabled us to generate important and timely insights that enable improvements to the delivery of COVID-19 vaccine schedules in a post-pandemic UK.”
The University of Cambridge team – jointly led by Dr James Thaventhiran, from the MRC Toxicology Unit and Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science – studied people with severe obesity attending the Obesity clinic at Addenbrooke’s Hospital in Cambridge, and compared the number and function of immune cells in their blood to those of people of normal weight.
They studied people six months after their second vaccine dose and then looked at the response to a third 'booster' vaccine dose over time. The Cambridge researchers found that six months after a second vaccine dose, people with severe obesity had similar levels of antibodies to the COVID-19 virus as those with a normal weight.
But the ability of those antibodies to work efficiently to fight against the virus (known as ‘neutralisation capacity’) was reduced in people with obesity. 55% of individuals with severe obesity were found to have unquantifiable or undetectable ‘neutralising capacity’ compared to 12% of people with normal BMI.
“This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection,” said Dr Agatha van der Klaauw from the Wellcome-MRC Institute of Metabolic Science and first author of the paper. “We urgently need to understand how to restore immune function and minimise these health risks.”
The researchers found that antibodies produced by people with severe obesity were less effective at neutralising the SARS-CoV-2 virus, potentially because the antibodies were not able to bind to the virus with the same strength.
When given a third (booster) dose of a COVID-19 vaccine, the ability of the antibodies to neutralise the virus was restored in both the normal weight and severely obese groups. But the researchers found that immunity again declined more rapidly in people with severe obesity, putting them at greater risk of infection with time.
Dr James Thaventhiran, a Group Leader from the MRC Toxicology Unit in Cambridge and co-lead author of the SCORPIO study said: “It is promising to see that booster vaccines restore the effectiveness of antibodies for people with severe obesity, but it is concerning that their levels decrease more quickly, after just 15 weeks. This shows that the vaccines work as well in people with obesity, but the protection doesn’t last as long.”
Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science and co-lead author of the SCORPIO study said: “More frequent booster doses are likely to be needed to maintain protection against COVID-19 in people with obesity. Because of the high prevalence of obesity across the globe, this poses a major challenge for health services”.
Reference
A A van der Klaauw et al., ‘Accelerated waning of the humoral response to COVID-19 vaccines in obesity’, Nature Medicine (2023). DOI: 10.1038/s41591-023-02343-2
The protection offered by COVID-19 vaccination declines more rapidly in people with severe obesity than in those with normal weight, scientists at the Universities of Cambridge and Edinburgh have found. The study suggests that people with obesity are likely to need more frequent booster doses to maintain their immunity.
COVID-19CoronavirusObesitySadaf FarooqiJames ThaventhiranAgatha van der KlaauwUniversity of EdinburghNIHR BioresourceUK Research and Innovation (UKRI)MRC Toxicology UnitWellcome-MRC Institute of Metabolic ScienceThis poses a major challenge for health servicesSadaf FarooqiSteven CornfieldPatient receiving a COVID-19 vaccination in their arm
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Exceptional scientists elected as Fellows of the Royal Society
The Royal Society is a self-governing Fellowship of many of the world’s most distinguished scientists drawn from all areas of science, engineering and medicine.
The Society’s fundamental purpose, as it has been since its foundation in 1660, is to recognise, promote and support excellence in science and to encourage the development and use of science for the benefit of humanity.
This year, a total of 80 researchers, innovators and communicators from around the world have been elected as Fellows of the Royal Society for their substantial contribution to the advancement of science. These include 59 Fellows, 19 Foreign Members and two Honorary Fellows.
Sir Adrian Smith, President of the Royal Society said: “I am delighted to welcome our newest cohort of Fellows. These individuals have pushed forward the boundaries of their respective fields and had a beneficial influence on the world beyond. This year’s intake have already achieved incredible things, and I have no doubt that they will continue to do so. I look forward to meeting them and following their contributions in future.”
The Fellows and Foreign Members join the ranks of Stephen Hawking, Isaac Newton, Charles Darwin, Albert Einstein, Lise Meitner, Subrahmanyan Chandrasekhar and Dorothy Hodgkin.
The Cambridge Fellows are:
Professor Cathie Clarke FRS
Professor of Theoretical Astrophysics, Institute of Astronomy
Clarke studies astrophysical fluid dynamics, including accretion and protoplanetary discs and stellar winds. She was the first to demonstrate how protoplanetary disc formation around low-mass young stars is determined by their radiation field. In 2017 she became the first woman to be awarded the Eddington Medal by the Royal Astronomical Society and in 2022 she became director of the Institute of Astronomy.
She said: “It's a great honour to join the many Cambridge astrophysicists who have held this title.”
Professor Christopher Jiggins FRS
Professor of Evolutionary Biology (2014), Department of Zoology, and Fellow of St Catharine’s College
Jiggins studies adaption and speciation in the Lepidoptera (butterflies and moths). In particular he is interested in studying how species converge due to mimicry as a model for understanding the predictability of evolution and the genetic and ecological causes of speciation. He demonstrated the importance of hybridisation and movement of genes between species in generating novel adaptations. He also works on cotton bollworm, an agricultural pest, and genomic studies of the insect bioconversion species, black soldier fly.
He said: “I am amazed and delighted to receive this honour, and would thank all the amazing students, and postdocs that I have been lucky enough to work with over the years.”
Dr Philip Jones FRS
Senior Group Leader, Wellcome Sanger Institute and Professor of Cancer Development, University of Cambridge
Jones studies how normal cell behaviour is altered by mutation in aging and the earliest stages of cancer development. He focuses on normal skin and oesophagus, which become a patchwork of mutant cells by middle age. He has found that different mutations can either promote or inhibit cancer development giving hope of new ways to prevent cancer in the future. He is also a Consultant in Medical Oncology at Addenbrooke’s Hospital in Cambridge.
He said: “I am delighted to be elected to the Fellowship of the Royal Society. This honour is a tribute to the dedication of my research team and collaborators and support of my mentors and scientific colleagues over many years.”
Dr Lori Passmore FRS
Group Leader, Structural Studies Division, MRC Laboratory of Molecular Biology and Fellow of Clare Hall
Passmore a cryo-electron microscopist and structural biologist who works at the Medical Research Council (MRC) Laboratory of Molecular Biology and at the University of Cambridge. She is known for her work on multiprotein complexes involved in gene expression and the development of new supports for cryo-EM studies. She also studies the molecular mechanisms underlying Fanconi anemia, a rare genetic disease resulting in an impaired response to DNA damage.
“I am so honoured to be recognised alongside such an exceptional group of scientists. I am grateful to all the trainees, collaborators and colleagues whom I have worked with over the past years - science is truly collaborative and this is a recognition of all the courageous work of many people.”
Professor Peter Sewell FRS
Professor of Computer Science, Department of Computer Science and Technology
Sewell’s research aims to put the engineering of the real-world computer systems that we all depend on onto better foundations, developing techniques to make systems that are better-understood, more robust and more secure. He and his group are best known for their work on the subtle relaxed-memory concurrency behaviour and detailed sequential semantics of processors and programming languages. He co-leads the CHERI cybersecurity project, for which his team have established mathematically-proven security properties of Arm's Morello industrial prototype architecture.
He said: “This honour is a testament to the work of many excellent colleagues over the years, without whom none of this would have been possible.”
Professor Ivan Smith FRS
Professor of Geometry, Centre for Mathematical Sciences
Smith is a mathematician who deals with symplectic manifolds and their interaction with algebraic geometry, low-dimensional topology and dynamics. In 2007, he received the Whitehead Prize for his work in symplectic topology, highlighting the breadth of applied techniques from algebraic geometry and topology, and in 2013 the Adams Prize.
He said: “I am surprised, delighted and hugely honoured to be elected a Fellow of the Royal Society. I’ve been very fortunate to work in a rapidly advancing field, learning it alongside many inspirational and generous collaborators, who should definitely share this recognition.”
Professor William Sutherland CBE FRS
Miriam Rothschild Chair of Conservation Biology, Department of Zoology and Professorial Fellow of St Catharine’s College
Sutherland is a conservation scientist who is interested in improving the processes by which decisions are made. This has involved horizon scanning to identify future issues to reduce the surprises of future developments. His main work has been the industrial-scale collation of evidence to determine which interventions are effective and which are not and then establishing processes for embedding evidence in decision making. He has developed a free, online resource, Conservation Evidence, summarising evidence for the effectiveness of conservation actions to support anyone making decisions about how to maintain and restore biodiversity and an open access book Transforming Conservation: a practical guide to evidence and decision making.
He said: “I am delighted that our work on the means of improving decision making in conservation and elsewhere has been recognised in this way and thank my numerous collaborators.”
Seven outstanding Cambridge researchers have been elected as Fellows of the Royal Society, the UK’s national academy of sciences and the oldest science academy in continuous existence.
Royal SocietyCathie ClarkeChris JigginsPhilip JonesLori PassmorePeter SewellIvan SmithWilliam SutherlandThe Royal SocietyInstitute of AstronomyDepartment of ZoologyWellcome Sanger InstituteMedical Research Council (MRC) Laboratory of Molecular BiologyClare HallDepartment of Computer Science and TechnologyCentre for Mathematical SciencesSt Catharine's CollegeSt John's CollegeSchool of Biological SciencesSchool of Physical SciencesSchool of TechnologySchool of Clinical MedicineSchool of the Physical SciencesSchool of the Biological SciencesThese individuals have pushed forward the boundaries of their respective fields and had a beneficial influence on the world beyond.Sir Adrian Smith, President of the Royal Society Courtesy of The Royal SocietyThe Royal Society, London
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Majority of NHS Trusts do not offer training to prevent sexual harassment, study finds
An analysis of data from Freedom of Information (FOI) requests found that fewer than one in five NHS Trusts in England provided active bystander training to address workplace harassment, sexual harassment and other forms of unacceptable behaviour like bullying and racism.
It found of those that did – the majority of which were in London – most did not deliver content specific to sexual misconduct and participation was voluntary.
Since 2017, when the #MeToo movement gained momentum around the world, sexual harassment in medicine has been recognised as both pervasive and harmful. This form of harassment – which includes a range of verbal, online and physical acts, ranging from poor taste jokes to unwanted touching to rape – can have a major impact on the individuals it affects and on the healthcare workforce itself.
In 2019, a survey by UNISON found that 8% of respondents had experienced sexual harassment while at work during the last 12 months, with more than half (54%) of these acts being perpetrated by co-workers.
Active bystander training encourages individuals to recognise and respond to poor behaviour, by equipping people with skills to intervene. Workshops and training programmes typically involve role-playing, case studies, and group participatory discussions.
To assess the extent to which such training programmes are being used within the NHS, researchers from Cambridge Public Health and the Intellectual Forum at Jesus College, Cambridge, submitted FOI requests to 213 NHS Trusts across England in December 2021. Their analysis is published today in JRSM Open.
Of the 199 Trusts (93%) that responded, only 35 offered active bystander training. Just five of the Trusts said their training addressed sexual harassment in some form, with the remaining 30 Trusts saying their training taught participants to challenge antisocial behaviour only in a general context. Only one Trust delivered content that specifically tackled sexual harassment in the workplace as its focus.
The majority of the Trusts that offered active bystander training were in London – 22 out of the 35. But even 14 of London’s NHS Trusts offered no training, despite the training being paid for by NHS England, not individual Trusts.
Among the 164 Trusts not offering active bystander training, only 23 Trusts had plans to implement it in the future. One Trust stated that they were actively developing plans to develop sexual safety training that will incorporate active bystander training. Several Trusts suggested they would consider implementing it if there was, to quote one of these Trusts, a “need for this form of training”, while other Trusts suggested implementation would occur if members of staff or working groups within the Trusts’ organisation advocated for it.
Dr Sarah Steele from Cambridge Public Health and Jesus College, Cambridge, said: “The NHS is failing to take advantage of a very effective training tool to address workplace harassment, sexual harassment and other forms of unacceptable behaviour such as bullying and racism. It’s a tool well used by the military, universities and educators, and which even the UN and UK government promotes.
“We found low uptake of active bystander training among NHS Trusts in England, particularly outside of London, and very little of the training that was on offer focused on sexual harassment. This is deeply worrying, given the continued problem of sexual harassment in the healthcare sector.
“Organisations need to encourage active bystander training from the very first days of undergraduate degrees through to the day of retirement. Without this, the problems of sexual harassment will continue to be a problem in the NHS and across wider society.”
Most of the Trusts used training programmes delivered by external companies – 27 out of the 35, with three Trusts not providing data. This meant that the researchers were unable to assess the content or effectiveness of the training programmes as they were commercial in confidence. While outsourcing training is meant to increase competition, the researchers found that one provider dominates.
Dr Ava Robertson, who carried out the research while part of the Population Health Sciences Partnership at the University of Cambridge University, said: “The problem with turning to private providers is that training materials can’t be externally audited, making it extremely difficult to evaluate how effective the programmes are. In some cases, it also meant that attendees of the workshops weren’t allowed to share the toolkits they received with other colleagues, so the knowledge isn’t more widely disseminated.”
The Home Office has been actively promoting active bystander training interventions to reduce sexual harassment and violence against women and girls more widely. Dr Steele, who sat on the campaign advisory group said cross-departmental learning from this campaign would support the Department of Health and Social Care, and the NHS, in thinking about behaviour change interventions amongst healthcare staff.
In 2021, on the back of the researchers’ work, Jesus College partnered with learning platform edX to offer free, online active bystander training available to anyone anywhere in the world.
Dr Steele who leads the course, and is Deputy Director of Jesus College’s Intellectual Forum said: “This course draws on up-to-date research and evidence on action and inaction, and offers real-world examples to help people respond at work, in public, and even at home. It can be accessed by anyone in the world for free so in the face of a lack of workplace training, individuals can still equip themselves with these essential skills.”
Reference
Robertson, A, and Steele, S. A cross-sectional survey of English NHS Trusts on their uptake and provision of active bystander training including to address sexual harassment. JRSM Open; 5 May 2023
Failure to implement active bystander training could thwart NHS attempts to tackle sexual harassment, say researchers at the University of Cambridge.
National Health Service (NHS)Spotlight on public healthSarah SteeleAva RobertsonSchool of Clinical MedicineCambridge Public HealthJesus CollegeThe NHS is failing to take advantage of a very effective training tool to address workplace harassment, sexual harassment and other forms of unacceptable behaviour such as bullying and racismSarah Steelesturti (Getty Images)Medical team strategy planning
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Wellcome awards Cambridge £18 million for two Discovery Research Platforms
The Discovery Research Platforms (DRPs) will be home to transformative research environments that empower researchers to overcome specific barriers holding back progress in their fields of research. They aim to accelerate research for the benefit of the wider global research community, with researchers and teams developing new tools, knowledge and capabilities to help unlock new findings about life, health and wellbeing.
Michael Dunn, Director of Discovery Research at Wellcome, said: “Discovery research is essential to advancing our ability to understand and improve health. But in addition to researchers’ bold and imaginative ideas, we know that new tools, methods and capabilities are also needed to unlock new avenues of research that can disrupt and transform the research landscape globally.”
The two Cambridge DRPs, which will receive £9million each over seven years, are:
The Discovery Research Platform for Tissue Scale Biology – which seeks to move stem cell biology to the tissue and organ scale of research, creating a new network of local and international researchers to enable strategies that capitalise on new in vitro models to develop better treatments for human patients.
Professor Bertie Gottgens, Director of the Wellcome-MRC Cambridge Stem Cell Institute, said: "I am delighted that Wellcome will support our ambition to build a new Discovery Research Platform to provide international leadership for Tissue Scale Biology.
“Our vision for this platform resulted from extensive discussions across the wider Cambridge Stem Cell community and the formation of a highly interdisciplinary team connecting the Cambridge Stem Cell Institute with the West Cambridge Engineering/Technology community. It also incorporates exciting new training partnerships with Anglia Ruskin University and the Cambridge Academy for Science and Technology, to help us fill critical skills shortages and widen participation across Cambridge."
The Discovery Research Platform for Integrating Metabolic and Endocrine Science – which aims to address practical barriers preventing data integration across metabolic and endocrine science, investigate how hormones control metabolic processes and how these can go wrong in disorders such as obesity, diabetes and cachexia, and create tools to facilitate global access to this data. The Platform will encompass research on molecules, cells and model organisms but will have a major focus on discovery science in human participants, patients and populations.
The funding will sustain key technological platforms and the highly-trained staff needed to support these. It will also underpin partnerships with research centres across the UK as well as in Germany and Denmark, all of which will provide new opportunities for training.
The Platform will have a major focus on the broad dissemination of integrated data and the creation of tools to facilitate access by the global community. The award will also accelerate the team’s drive to make transformational changes to research culture with new initiatives in widening access and open science reinforced by a new programme of research into the culture of biomedical science, in collaboration with the Cambridge Judge Business School.
Professor Sir Stephen O’Rahilly, Co-Director at the Wellcome-MRC Institute of Metabolic Science and Director of the MRC Metabolic Diseases Unit, said: “Wellcome’s support of our scientists’ research in metabolism and endocrinology, and of the technological platforms that underpin it, has been critically important to the discoveries we have made and the translation of that research into improvements in health. This new award will allow us to build on those achievements and deliver more ground-breaking science in a manner that emphasises openness, diversity and a spirit of collaboration.”
Cambridge has been awarded two of Wellcome’s eight new Discovery Research Platforms, the global charitable foundation announced today.
Stem cellsmetabolismBertie GottgensStephen O’RahillyCambridge Academy for Science and TechnologyAnglia Ruskin UniversityWellcomeSchool of Clinical MedicineWellcome-MRC Cambridge Stem Cell InstituteWellcome-MRC Institute of Metabolic ScienceCambridge Judge Business SchoolOdra NoelAcinar tissue - The flowers of diabetes
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Search is on for ‘super memorisers’ to help scientists unlock the secrets of memory
Anyone who believes they have an exceptional memory is invited to take an online survey and memory test. Based on their performance, some people will be invited to Cambridge to have a brain scan so that the origins of exceptional memory can be explored in detail.
The team will also be exploring whether people who are autistic or neurodiverse are more likely to have an exceptional memory.
It’s long been known that people differ in their memory ability, with some having seemingly infinite memory. For example, essayist and writer Daniel Tammet, who the Cambridge team have worked with previously, set the European record in 2004 for reciting the number pi from memory after recalling it to 22,514 digits. He is both autistic and has synaesthesia, where the senses are interconnected, which may go some way to explaining his talents.
Professor Jon Simons from the Department of Psychology at the University of Cambridge said: “Memory is one of the best understood psychological processes in terms of brain networks and yet we still don’t really know why some people have exceptional memories. That’s why we’re inviting people to take part in our study.”
Professor Sir Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge University, and lead investigator of the study, said: “You don’t need to have won any competitions to take part or to consider yourself neurodiverse – and you certainly don’t need to be able to recite pi to 22,000 digits! We’re looking for anyone who thinks they might be a ‘super memoriser’ to try out our memory tests.”
Anyone who wants to take part will need to take three brief online memory tests, such as memorising a phone number or patterns on a chess board. Anyone who scores highly on one or more of these tests could be invited to come to Cambridge for a brain scan using an MRI scanner. All expenses will be paid.
The Cambridge scientists want to know whether the brains of people who have exceptional memory show differences in how they are structured or how they function compared to those who do not: in short, how do they achieve their remarkable feats of memory? The team also want to investigate if autism gives rise to a greater likelihood of exceptional memory.
Dr Carrie Allison, also from the Autism Research Centre, added: “We hope that people will enjoy taking part in this study, and in the process contribute to helping us understand more about memory and whether exceptional memory is related to autism. For decades, autism research has focused on disability, but this study is a wonderful opportunity to focus on strengths.”
To take part you must be between the ages of 16 and 60 years old.
Take the survey and memory tests hereCambridge scientists are today launching a search to find people who have exceptional memory, as they attempt to understand why some people are much better at remembering than others.
memoryautismSpotlight on neuroscienceJon SimonsSimon Baron-CohenCarrie AllisonSchool of Clinical MedicineSchool of the Biological SciencesAutism Research CentreDepartment of PsychiatryDepartment of PsychologyCambridge NeuroscienceTrinity CollegeMemory is one of the best understood psychological processes in terms of brain networks and yet we still don’t really know why some people have exceptional memoriesJon SimonsgeraltPi on a blackboard
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Dogs may be at risk from high levels of lead from shotgun pellets in raw pheasant dog food, study finds
Lead is a toxic metal that negatively affects body systems of people and animals, with the nervous system being particularly sensitive. Although elevated levels of dietary lead are potentially damaging to animal health, lead shot can be legally used for hunting terrestrial gamebirds, like pheasants, in the UK. While most pheasants are eaten by people, some are used in petfood.
Cambridge researchers analysed 90 samples taken from three raw pheasant dog food products bought in the UK and found that 77% of samples had lead concentrations exceeding the maximum residue level (MRL) permitted in animal feed according to law. Mean lead concentrations of the three products were approximately 245, 135 and 49 times higher than the MRL.
The results are published today in the journal Ambio.
“We were already aware that lead concentrations in pheasant meat sold for human consumption are often far higher than would be permitted in other meats like chicken, beef or pork” said lead author Professor Debbie Pain of Cambridge’s Zoology Department. “However, we were surprised to find that lead concentrations in raw pheasant dog food products were so much higher”
The mean lead concentration in the raw pheasant dog food analysed was 34 times higher than that recently reported in pheasant meat sold for people to eat, which itself is considered to be too high. Researchers say this could be because raw pheasant meat is normally minced when used for dogfood whereas whole birds or pheasant breasts are generally sold for human consumption. Mincing may fragment lead shot, increasing the number of small lead particles in the meat and the potential for lead to be absorbed into the bloodstream.
The researchers say that dogs eating food with such high concentrations of lead, especially if they are fed on it frequently or as their main diet, are at risk of harm to their health. Puppies are particularly vulnerable both because young animals tend to absorb more of the lead they swallow than full-grown animals, and the developing nervous system is particularly affected by lead.
The scientists tested five pheasant-based dog food products. Three of these were raw meat products, one was a dried pheasant and partridge product, and one was a processed tinned pheasant and goose-based product. Three equivalent chicken-based petfood products (raw meat, dried and processed) were also assessed.
In addition to the raw pheasant dog food, levels of lead above the MRL were identified in some samples of the dried pheasant-based product, although the mean concentration was far lower than in the raw products. None of the samples from the chicken-based products or the tinned pheasant and goose-based product contained unacceptable levels of lead.
The popularity of raw meat diets for pets is increasing across the UK – a nation which is home to an estimated 13 million dogs and 12 million cats. The researchers found that raw dog food including pheasant meat was widely available in the UK. Raw pheasant pet food was sold by 34% of the 50 online raw pet food suppliers they checked – 71% of these stated that the meat may contain shot.
“The fact that most samples from three randomly sampled raw pheasant pet food products had very high lead concentrations, and that our recent research on shot types used to kill pheasants found that 94% are shot with lead, suggests that this is a far broader issue than for just these three products,” said co-author Professor Rhys Green. “However, some producers may source pheasants that have not been shot with lead, and owners could ask about this when buying pet food.”
The study of shot types in pheasants sold for human consumption is part of a body of research assessing the effectiveness of a voluntary ban in the UK on lead shotgun ammunition to shoot wild quarry, which is being phased in over a five-year period from February 2020. Nine major shooting organisations committed to this, for sustainability reasons, considering wildlife, the environment and also to ensure a market for the healthiest game products.
Cambridge scientists have consistently found compliance with the voluntary ban to be low, which is in line with other studies investigating other voluntary bans. However, a total ban in Denmark has been shown to be very effective.
A ban on the sale and use of lead gunshot, along with restrictions on lead bullets, is currently being considered under the UK REACH Chemicals Regulation.
The analytical costs of this research were funded by Wild Justice.
D. Pain, R. E. Green, N. Bates, M. Guiu, M. A. Taggart, Lead concentrations in commercial dogfood containing pheasant in the UK, Ambio. DOI: 10.1007/s13280-023-01856-x
Researchers tested samples of raw pheasant dog food and discovered that the majority contained high levels of lead that could put dogs’ health at risk if they eat it frequently.
dogsEnvironmentSustainable EarthDebbie PainRhys GreenDepartment of ZoologySchool of Biological SciencesSchool of the Biological Sciences24K-Production / iStock / Getty Images PlusDog eating raw meat
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The mystery of Robinson Crusoe's seals
By Louise Walsh
Published 30 April 2023
Juan Fernández fur seal
Juan Fernández fur seal
Dr Constanza Toro-Valdivieso has been to the ends of the Earth to collect seal poo.She’s known as la niña de las cacas, or the poo girl, in the Chilean islands of Juan Fernández.
The samples she collects are providing valuable information about a little-studied species that came back from the brink of extinction.
Her results show these seemingly healthy seals are contaminated by toxic heavy metals.
The only known breeding ground for the Juan Fernández fur seal is an archipelago 500 miles off the coast of Chile in the South Pacific Ocean.
Discovered in the 1500s, the fur seals were then hunted almost to extinction in the centuries that followed. A small number of seals survived and were rediscovered in the 1960s.
Since then, a 30-year hunting ban enabled the population to grow. The ban will be reassessed by the Chilean government in 2025.
Despite this survival story, the species remains poorly understood.
Journey to Robinson Crusoe’s island Constanza Toro-Valdivieso was studying to be a vet in her home country of Chile when she first read about the fur seals of Juan Fernández.The archipelago is probably best known for the story of Alexander Selkirk, a Scottish privateer marooned there from 1704 to 1709 whose story is thought to have inspired Daniel Defoe’s 1719 novel The Life and Strange Surprizing Adventures of Robinson Crusoe of York, Mariner. In the hopes of boosting tourism, the Chilean government decided to rename the three islands Alejandro Selkirk, Robinson Crusoe and Santa Clara in the 1960s.
Today, this one-time pirate hideout and penal colony is home to one of the least known species of fur seals on the planet.
But reaching them is no small matter. On her 7,600 mile journey from Cambridge to Robinson Crusoe Island, Constanza has met with leaky boats, bad weather and closure of the islands for fire risk.
Why study the fur seals? Because this knowledge would be a valuable contribution to monitoring and managing the protected marine ecosystem around the islands, says Constanza from Cambridge’s Department of Veterinary Medicine.
“Even though Juan Fernández has been identified by UNESCO as being important for its biodiversity, resources for observing and enhancing conservation in the region are scarce,” she explains.
“Identifying and studying ‘charismatic’ species like fur seals can have an essential role in promoting awareness and action. But information on the fur seals is limited and outdated. I wanted to create a ‘benchmark’ of their health so that we can measure changes in the future.”
And the benefits extend beyond protecting the fur seal population to protecting the health of our seas.
“Because these are marine animals, their health tells us about the oceans they inhabit, like a sort of ‘canary in the coalmine’ of the seas. For instance, warming of the seas by climate change affects abundance of prey and mating behaviour.”
Marine pollution is another critical factor...
“A few hundred miles to the west of the Juan Fernández archipelago is a huge area of plastic contamination 18 times the size of the UK.”“We know that plastic debris, which can be may be micro- or even nano-sized, absorbs toxic heavy metals such as cadmium and mercury released into the seas by human activities like mining and oil extraction.
“We also know that marine mammals can be highly exposed to heavy metals particularly if, as fur seals do, they feed on species like octopus and squid.
“Although the Juan Fernández fur seals live in an almost pristine environment, their foraging grounds coincide with the area of plastic pollution. What effect, we wondered, would this have on them?”
Image captions- Image 1
Constanza Toro-Valdivieso (credit: Louise Walsh)
Constanza Toro-Valdivieso (credit: Louise Walsh)
Constanza Toro-Valdivieso (credit: Louise Walsh)
“You’re making your way through a sea of noisy creatures that look at you curiously, deciding how to react, and then a strong smell hits you.” “It’s a mix of rotten fish and ammonia so pungent and unpleasant it brings tears to your eyes.” “But then the excitement kicks in. You’ve found your first sample of fur seal poo. At that moment, I learnt an important lesson, bad smells equal success.” Winning the Poo Collecting poo can tell you a lot about an animal’s well-being because what happens in the gut can be detected in the faeces.As a veterinary scientist, Constanza knew that valuable clues on health and disease could be revealed through looking at the makeup of the microbiome – the trillions of microorganisms in the gut that support the healthy daily working of the body but can change depending on environmental stress, diet and disease.
She applied for a PhD at the Department of Veterinary Medicine with Dr Barbara Blacklaws, an expert on how the faecal microbiome of wildlife can be used as a non-invasive way to determine the health of populations.
On field trips, National Forest Corporation park rangers helped her with transportation from the small settlement of San Juan Bautista to the seal colonies on uninhabited islands. There she would spend her days searching for seal poo, carefully bagging and logging samples, ready for analysis back in the Cambridge lab.
“I am known by the community of Juan Fernández as la niña de las cacas – the poo girl.”Several years on from her first field trip in 2016, she has now completed her PhD, and created and analysed a ‘seal poo library’ of over 70 samples.
Toxic discovery Constanza tested the samples she’d collected to see if they showed evidence of contamination. They did. In fact Juan Fernández fur seals are contaminated with one of the highest levels of toxic heavy metals ever reported in an animal.The recently published research, which she carried out in collaboration with Professor Jonathan Powell, Director of Biomineral Research and Imaging at the Department of Veterinary Medicine, showed very high concentrations of cadmium in the faecal samples,. Concentrations were also high in samples of seal bone found on the beach.
“Cadmium levels were 57 times higher than samples from Antarctic fur seals [supplied by the British Antarctic Survey], and more than 200 times higher than those reported in the faeces collected from children inhabiting a cadmium-polluted mining town in Zambia.”
She started to look for the source. The island soil was free of this contamination. But the seals’ prey was not. Her studies showed that the hepatopancreas (an organ that humans discard when eating octopus) of locally caught octopus showed high concentrations of cadmium.
“We think cadmium enters the food chain after being metabolised by ocean phytoplankton. We don’t yet know whether the source is natural or anthropogenic, but we think it’s likely the food chain is becoming enriched in toxins by pollution,” says Constanza. “Further studies will be needed.”
Another mystery is why the fur seals appear so healthy despite such high levels of a toxic metal known to be associated with osteoporosis. “We may have a clue, but again further research is needed,” she says. “We discovered high levels of silicon in the bones and wonder if the silicon is playing a protective role.”
What does this all mean for the survival of the species?
The absolute numbers of fur seals have been increasing since their rediscovery in the 1960s.
“With the re-assessment of the hunting ban in two years time, I hope that my research will inform policymakers on deciding future strategies on conservation and be a valuable step forward in understanding the threats to the fur seals in this remote part of the world.”
Image captions- Image 1
Plastic debris in Juan Fernández
Plastic debris in Juan Fernández
Plastic debris in Juan Fernández
Constanza was funded by the Chilean National Research and Development Agency and a Newnham College travel grant. Her fieldwork would not have been possible without the support of park rangers from the National Forest Corporation (CONAF) and the community of Juan Fernández. She is currently collaborating with Fundacion Endemica, a Chilean non-profit organisation working in the islands, to support the local community to keep learning more about the fur seals.
Published 30 April 2023
With thanks to Constanza Toro-Valdivieso
Written by Louise Walsh
Photography by Constanza Toro-Valdivieso
Film by Jonathan Settle
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
TopBuilt with Shorthand Hidden tags: storiesSummary:Dr Constanza Toro-Valdivieso has been to the ends of the Earth to collect seal poo. Her results show that seemingly healthy seals are contaminated by toxic heavy metals.
Image: Affiliation (schools and institutions): Department of Veterinary MedicineSchool of Clinical MedicinePeople (our academics and staff): Constanza Toro-ValdiviesoBarbara BlacklawsJonathan PowellSubject (including Spotlight on ... where applicable): Sustainable EarthconservationbiodiversityChileEnvironmentpollutionsealsStoriesSection: ResearchNews type: FeaturesSuper Tags: EnvironmentShorthand Story Description/Subtitle: Dr Constanza Toro-Valdivieso has been to the ends of the Earth to collect seal poo. Her results show that seemingly healthy seals are contaminated by toxic heavy metals.Shorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/238621/hYX6yp1aUt/assets/qZMsYfd7nZ/dscn1183-2560by1440v2-thumbnail.jpgHIV drug helps protect against build-up of dementia-related proteins in mouse brains
A common characteristic of neurodegenerative diseases such as Huntington’s disease and various forms of dementia is the build-up in the brain of clusters – known as aggregates – of misfolded proteins, such as huntingtin and tau. These aggregates lead to the degradation and eventual death of brain cells and the onset of symptoms.
One method that our bodies use to rid themselves of toxic materials is autophagy, or ‘self-eating’, a process whereby cells ‘eat’ the unwanted material, break it down and discard it. But this mechanism does not work properly in neurodegenerative diseases, meaning that the body is no longer able to get rid of the misfolded proteins.
In a study published today in Neuron, a team from the Cambridge Institute for Medical Research and the UK Dementia Research Institute at the University of Cambridge has identified a process that causes autophagy not to work properly in the brains of mouse models of Huntington’s disease and a form of dementia – and importantly, has identified a drug that helps restore this vital function.
The team carried out their research using mice that had been genetically-altered to develop forms of Huntington’s disease or a type of dementia characterised by the build-up of the tau protein.
The brain and central nervous system have their own specialist immune cells, known as microglia, which should protect against unwanted and toxic materials. In neurodegenerative diseases, the microglia kick into action, but in such a way as to impair the process of autophagy.
Using mice, the team showed that in neurodegenerative diseases, microglia release a suite of molecules which in turn activate a switch on the surface of cells. When activated, this switch – called CCR5 – impairs autophagy, and hence the ability of the brain to rid itself of the toxic proteins. These proteins then aggregate and begin to cause irreversible damage to the brain – and in fact, the toxic proteins also create a feedback loop, leading to increased activity of CCR5, enabling even faster build-up of the aggregates.
Professor David Rubinsztein from the UK Dementia Research Institute at the University of Cambridge, the study’s senior author, said: “The microglia begin releasing these chemicals long before any physical signs of the disease are apparent. This suggests – much as we expected – that if we’re going to find effective treatments for diseases such as Huntington’s and dementia, these treatments will need to begin before an individual begins showing symptoms.”
When the researchers used mice bred to ‘knock out’ the action of CCR5, they found that these mice were protected against the build-up of misfolded huntingtin and tau, leading to fewer of the toxic aggregates in the brain when compared to control mice.
This discovery has led to clues to how this build-up could in future be slowed or prevented in humans. The CCR5 switch is not just exploited by neurodegenerative diseases – it is also used by HIV as a ‘doorway’ into our cells. In 2007, the US and European Union approved a drug known as maraviroc, which inhibits CCR5, as a treatment for HIV.
The team used maraviroc to treat the Huntington’s disease mice, administering the drug for four weeks when the mice were two months old. When the researchers looked at the mice’s brains, they found a significant reduction in the number of huntingtin aggregates when compared to untreated mice. However, as Huntington’s disease only manifests in mice as mild symptoms by 12 weeks even without treatment, it was too early to see whether the drug would make an impact on the mice’s symptoms.
The same effect was observed in the dementia mice. In these mice, not only did the drug reduce the amount of tau aggregates compared to untreated mice, but it also slowed down the loss of brain cells. The treated mice performed better than untreated mice at an object recognition test, suggesting that the drug slowed down memory loss.
Professor Rubinsztein added: “We’re very excited about these findings because we’ve not just found a new mechanism of how our microglia hasten neurodegeneration, we’ve also shown this can be interrupted, potentially even with an existing, safe treatment.
“Maraviroc may not itself turn out to be the magic bullet, but it shows a possible way forward. During the development of this drug as a HIV treatment, there were a number of other candidates that failed along the way because they were not effective against HIV. We may find that one of these works effectively in humans to prevent neurodegenerative diseases.”
The research was supported by Alzheimer’s Research UK, the UK Dementia Research Institute, Alzheimer’s Society, Tau Consortium, Cambridge Centre for Parkinson-Plus, Wellcome and the European Union's Horizon 2020 research and innovation programme.
Reference
Festa, BP, Siddiqi, FH, & Jimenez-Sanchez, M, et al. Microglial-to-neuronal CCR5 signalling regulates autophagy in neurodegeneration. Neuron; 26 Apr 2023; DOI: 10.1016/j.neuron.2023.04.006
Cambridge scientists have shown how the brain’s ability to clear out toxic proteins is impaired in Huntington’s disease and other forms of dementia – and how, in a study in mice, a repurposed HIV drug was able to restore this function, helping prevent this dangerous build-up and slowing progression of the disease.
Spotlight on neuroscienceHuntington's DiseaseAlzheimer's diseasedementiaanimal researchDavid RubinszteinUK Dementia Research InstituteAlzheimer's Research UKAlzheimer's SocietyEuropean Union Horizon 2020School of Clinical MedicineCambridge Institute for Medical Research (CIMR)UK Dementia Research InstituteWe’re very excited about these findings because we’ve not just found a new mechanism of how our microglia hasten neurodegeneration, we’ve also shown this can be interruptedDavid RubinszteinUnderstanding Animal ResearchBrown mouse
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Almost half of people with concussion still show symptoms of brain injury six months later
Mild traumatic brain injury – concussion – results from a blow or jolt to the head. It can occur as a result of a fall, a sports injury or from a cycling accident or car crash, for example. But despite being labelled ‘mild’, it is commonly linked with persistent symptoms and incomplete recovery. Such symptoms include depression, cognitive impairment, headaches, and fatigue.
While some clinicians in recent studies predict that nine out of 10 individuals who experience concussion will have a full recovery after six months, evidence is emerging that only a half achieve a full recovery. This means that a significant proportion of patients may not receive adequate post-injury care.
Predicting which patients will have a fast recovery and who will take longer to recover is challenging, however. At present, patients with suspected concussion will typically receive a brain scan – either a CT scan or an MRI scan, both of which look for structural problems, such as inflammation or bruising – yet even if these scans show no obvious structural damage, a patient’s symptoms may still persist.
Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences and Division of Anaesthesia at the University of Cambridge said: “Worldwide, we’re seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population and rising numbers of road traffic collisions in low- and middle-income countries.
“At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms.”
Dr Stamatakis and colleagues studied fMRI brain scans – that is, functional MRI scans, which look at how different areas of the brain coordinate with each other – taken from 108 patients with mild traumatic brain injury and compared them with scans from 76 healthy volunteers. Patients were also assessed for ongoing symptoms.
The patients and volunteers had been recruited to CENTER-TBI, a large European research project which aims to improve the care for patients with traumatic brain injury, co-chaired by Professor David Menon (head of the division of Anaesthesia) and funded by the European Union.
In results published today in Brain, the team found that just under half (45%) were still showing symptoms resulting from their brain injury, with the most common being fatigue, poor concentration and headaches.
The researchers found that these patients had abnormalities in a region of the brain known as the thalamus, which integrates all sensory information and relays this information around the brain. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain – in other words, the thalamus was trying to communicate more as a result of the injury – and the greater this connectivity, the poorer the prognosis for the patient.
Rebecca Woodrow, a PhD student in the Department of Clinical Neuroscience and Hughes Hall, Cambridge, said: “Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain’s relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience.”
By studying additional data from positron emission tomography (PET) scans, which can measure regional chemical composition of body tissues, the researchers were able to make associations with key neurotransmitters depending on which long-term symptoms a patient displayed. For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin.
Dr Stamatakis, who is also Stephen Erskine Fellow at Queens' College, Cambridge, added: “We know that there already drugs that target these brain chemicals so our findings offer hope that in future, not only might we be able to predict a patient’s prognosis, but we may also be able to offer a treatment targeting their particular symptoms.”
Reference
Woodrow, RE et al. Acute thalamic connectivity precedes chronic postconcussive symptoms in mild traumatic brain injury. Brain; 26 April 2023; DOI: 10.1093/brain/awad056
Even mild concussion can cause long-lasting effects to the brain, according to researchers at the University of Cambridge. Using data from a Europe-wide study, the team has shown that for almost a half of all people who receive a knock to the head, there are changes in how regions of the brain communicate with each other, potentially causing long term symptoms such as fatigue and cognitive impairment.
Spotlight on neurosciencebrain injuryEmmanuel StamatakisRebecca WoodrowSchool of Clinical MedicineDepartment of Clinical NeurosciencesDivision of AnaesthesiaHughes HallQueens' CollegeThe combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptomsEmmanuel StamatakisAleksandarGeorgiev (Getty Images)Female Still In Shock After Getting Hit By Car With Motorcycle
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Problems with ‘pruning’ brain connections linked to adolescent mental health disorders
The findings, from an international collaboration, led by researchers in the UK, China and Germany, may help explain why people are often affected by more than one mental health disorder, and may in future help identify those at greatest risk.
One in seven adolescents (aged 10-19 years old) worldwide experiences mental health disorders, according to the World Health Organization (WHO). Depression, anxiety and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD), are among the leading causes of illness and disability among young people, and adolescents will commonly have more than one mental health disorder.
Many mental health problems emerge during adolescence. Among these are disorders such as depression and anxiety, which manifest as ‘internalising’ symptoms, including low mood and worrying. Other conditions such as attention deficit hyperactivity disorder (ADHD) manifest as ‘externalising’ symptoms, such as impulsive behaviour.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Young people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult life. This suggests that there’s a common brain mechanism that could explain the onset of these mental health disorders during this critical time of brain development.”
In a study published today in Nature Medicine, the researchers say they have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’, or NP factor for short.
The team examined data from 1,750 adolescents, aged 14 years, from the IMAGEN cohort, a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. In particular, they examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity – in other words, how different regions of the brain communicate with each other.
Adolescents who experienced mental health problems – regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders – showed similar patterns of brain activity. These patterns – the NP factor – were largely apparent in the frontal lobes, the area at the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behaviour.
The researchers confirmed their findings by replicating them in 1,799 participants from the ABCD Study in the USA, a long-term study of brain development and child health, and by studying patients who had received psychiatric diagnoses.
When the team looked at genetic data from the IMAGEN cohort, they found that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11 that has been previously associated with multiple mental health disorders. This gene is known to play an important role in synaptic pruning, a process whereby unnecessary brain connections – synapses – are discarded. Problems with pruning may particularly affect the frontal lobes, since these regions are the last brain areas to complete development in adolescents and young adults.
Dr Tianye Jia from the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK said: “As we grow up, our brains make more and more connections. This is a normal part of our development. But too many connections risk making the brain inefficient. Synaptic pruning helps ensure that brain activity doesn’t get drowned out in ‘white noise’.
“Our research suggests that when this important pruning process is disrupted, it affects how brain regions talk to each other. As this impact is seen most in the frontal lobes, this then has implications for mental health.”
The researchers say that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.
Professor Jianfeng Feng from Fudan University in Shanghai, China, and the University of Warwick, UK, said: “We know that many mental health disorders begin in adolescence and that individuals who develop one disorder are at increased risk of developing other disorders, too. By examining brain activity and looking for this NP factor, we might be able to detect those at greatest risk sooner, offering us more opportunity to intervene and reduce this risk.”
Funders included: the National Natural Science Foundation of China, European Union, National Institute for Health & Care Research (UK) and National Institutes of Health (NIH, USA).*
Reference
Chao Xie et al. A shared neural basis underlying psychiatric comorbidity. Nat Med; 24 Apr 2023: DOI: 10.1038/s41591-023-02317-4
*A full list of funders can be found in the paper.
Problems with the brain’s ability to ‘prune’ itself of unnecessary connections may underlie a wide range of mental health disorders that begin during adolescence, according to research published today.
Spotlight on neuroscienceMental healthadolescentsChildrenBarbara SahakianUniversity of WarwickKings College LondonFudan UniversitySchool of Clinical MedicineDepartment of PsychiatryCambridge NeuroscienceClare CollegeYoung people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult lifeBarbara SahakianWarren WongTeenager sitting near graffiti
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Cambridge University’s needle-free coronavirus vaccine begins clinical trials in home city
The vaccine – known as DIOS-CoVax – has been developed by Professor Jonathan Heeney at the University of Cambridge and spin-out company DIOSynVax. It is envisaged as a booster targeting SARS-CoV-2 and relatives that threaten future coronavirus pandemics.
This next generation vaccine is administered through a needle-free ‘injection’ – a blast of air that delivers it into the skin. It has already been part of safety trials conducted at the NIHR Southampton Clinical Research Facility, but now recruitment is being expanded to Cambridge.
Professor Heeney said: “We’re excited to be bringing our vaccine ‘home’ and are looking to recruit healthy volunteers to help in this crucial stage of development towards what we hope will eventually become a universal coronavirus vaccine.
“Our vaccine is innovative, both in terms of how it aims to protect against thevirus responsible for our current pandemic and future coronaviruses, but also in how it is delivered. If you’re someone who hates needles, our vaccine could be the answer as it’s delivered by a jet of air, not a needle.”
If the clinical trials are successful, the vaccine could be scaled up and manufactured as a powder to boost global vaccination efforts, particularly in low- and middle-income countries.
The clinical trials team at Cambridge University Hospitals NHS Foundation Trust is looking for healthy volunteers aged 18-50 to take part in the study. Volunteers will receive payment for their time, and participation on the trial will last around 12 months with volunteers attending 11 visits. To find out more, contact the Project Management Team at cuh.dioscovaxtrial@nhs.net.
Funding for the development of the vaccine has come from Innovate UK, part of UK Research and Innovation.
DIOSynVax is a spin-out company from the University of Cambridge, established in 2017 with the support of Cambridge Enterprise, the University’s commercialisation arm. Professor Heeney is a Fellow at Darwin College, Cambridge.
Read more at: Cambridge coronavirus vaccine enters clinical trialRecruitment is underway in Cambridge for volunteers to take part in clinical trials of a revolutionary new needle-free vaccine to protect against SARS-CoV-2 – the virus that causes COVID-19 – and related coronanviruses.
CoronavirusCOVID-19vaccinespotlight on future therapeuticsspotlight on innovationJonathan HeeneyDIOSynVaxSchool of the Biological SciencesDepartment of Veterinary MedicineLaboratory of Viral ZoonoticsCambridge Infectious DiseasesCambridge EnterpriseCambridge University Hospitals NHS Foundation TrustWe’re excited to be bringing our vaccine ‘home’ and are looking to recruit healthy volunteers to help in this crucial stage of developmentJonathan HeeneyLloyd Mann (University of Cambridge)Vaccine being administered by needle-free injection into a volunteer's arm
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International study recommends replacing skull section after treatment for a brain bleed
The RESCUE-ASDH trial, funded by the UK’s National Institute for Health and Care Research (NIHR), involved 40 centres in 11 countries and involved 450 patients. The results of the trial are published today in the New England Journal of Medicine and are announced at the annual meeting of the American Association of Neurological Surgeons.
One of the potentially life-threatening results of head injury is a so-called acute subdural haematoma – a bleed that occurs between the brain and skull and can lead to the build-up of pressure. Such haemorrhages require surgery to stem the bleeding, remove the blood clot and relieve the pressure.
At present, there are two approaches to such surgery. One approach is a decompressive craniectomy, which involves leaving a section of the skull out – which can be as large as 13cm in length – in order to protect the patient from brain swelling, often seen with this type of haemorrhage. The missing skull typically will need to be reconstructed and in some treatment centres, the patient’s own bone will be replaced several months after surgery, while at other centres a manufactured plate is used.
The second approach is a craniotomy, in which the skull section is replaced after the haemorrhage has been stemmed and the blood clot removed. This approach will obviate the need for a skull reconstruction further down the line.
To date there has been little conclusive evidence and hence no uniformly accepted criteria for which approach to use. To solve this question, an international team led by researchers at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust carried out a randomised trial – RESCUE-ASDH – in which patients undergoing surgery for traumatic acute subdural haematoma were randomly assigned to undergo decompressive craniectomy or craniotomy.
A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The researchers assessed the outcomes for these patients and their quality of life up to a year after surgery, as measured on clinical evaluation scales.
Patients in both groups had similar disability-related and quality-of-life outcomes at 12 months post-surgery, with a trend – which was not statistically significant – towards better outcomes with craniotomy.
Around one in four patients (25.6%) in the craniotomy group and one in five (19.9%) in the decompressive craniectomy group had a good recovery as measured on the scales.
Around one in three patients in both groups (30.2% of patients in the craniotomy group and 32.2% of those in the decompressive craniectomy group) died within the first 12 months following surgery.
14.6% of the craniotomy group and 6.9% of the decompressive craniectomy group required additional cranial surgery within two weeks after randomisation. However, this was balanced against the fact that fewer people in the craniotomy group experienced wound complications (3.9% against 12.2% of the decompressive craniectomy group).
Professor Peter Hutchinson, Professor of Neurosurgery at Cambridge and the trial's Chief Investigator, said: "The international randomised trial RESCUE-ASDH is the first multicentre study to address a very common clinical question: which technique is optimal for removing an acute subdural haematoma – a craniotomy (putting the bone back) or a decompressive craniectomy (leaving the bone out)?
“This was a large trial and the results convincingly show that there is no statistical difference in the 12 month disability-related and quality of life outcomes between the two techniques.”
Professor Angelos Kolias, Consultant Neurosurgeon at Cambridge and the trial's Co-chief Investigator, said: "Based on the trial findings, we recommend that after removing the blood clot, if the bone flap can be replaced without compression of the brain, surgeons should do so, rather than performing a pre-emptive decompressive craniectomy.
“This approach will save patients from having to undergo a skull reconstruction, which carries the risk of complications and additional healthcare costs, further down the line.”
The researchers point out, however, that the findings may not be relevant for resource-limited or military settings, where pre-emptive decompressive craniectomy is often used owing to the absence of advanced intensive care facilities for post-operative care.
Professor Andrew Farmer, Director of NIHR’s Health Technology Assessment (HTA) Programme, said: “The findings of this world-leading trial provide important evidence which will improve the way patients with head injuries are treated. High quality, independently funded research like this is vital in providing evidence to improve health and social care practice and treatments. Research is crucial in informing those who plan and provide care.”
The RESCUE-ASDH trial was supported by the NIHR Global Health Research Group on Acquired Brain and Spine Injury, the CENTER-TBI project of the European Brain Injury Consortium, and the Royal College of Surgeons of England Clinical Research Initiative.
Reference
Hutchinson, PJ et al. Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma. NEJM; 23 Apr 2023; DOI: 10.1056/NEJMoa2214172
A major international trial has concluded that, where possible, surgeons should replace the removed section of the skull following surgery to treat a form of brain haemorrhage. This approach will save patients from having to undergo skull reconstruction further down the line.
Spotlight on neuroscienceTraumatic brain injurysurgeryPeter HutchinsonAngelos KoliasNational Institute for Health Research (NIHR)School of Clinical MedicineDepartment of Clinical NeurosciencesCambridge NeuroscienceThis approach will save patients from having to undergo a skull reconstruction, which carries the risk of complications and additional healthcare costs, further down the lineAngelos Koliaswww.tredz.co.uk/Bike Crash - Road Traffic Accident
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Evolution of two contagious cancers affecting Tasmanian devils underlines unpredictability of disease threat
Transmissible cancers, which occur only rarely in the animal kingdom, are spread by the transfer of living cancer cells. In the case of Tasmanian devils, the cells are transferred through biting – a behaviour that is common in devils especially in fights over mates and food.
Tasmanian devils are susceptible to two fatal transmissible cancers called devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2) that have caused rapid population decline in recent decades. The two cancers both manifest with disfiguring facial tumours.
In a new study, University of Cambridge researchers, together with a global team of scientists from Europe, Australia and the United States, mapped the emergence and mutations of DFT1 and DFT2 and characterised these cancers’ ongoing evolution. The findings underline the continued threat that transmissible cancers pose to Tasmanian devils.
The results are published today in the journal Science.
“The incredible fact that Tasmanian devils have not one, but two, transmissible cancers, makes it possible to compare their evolution, and this gives us new insights into the key mechanisms involved,” said lead author Elizabeth Murchison, Professor of Comparative Oncology and Genetics at the Department of Veterinary Medicine, University of Cambridge.
“By looking at the mutations that have accumulated in these cancers’ DNA, we can trace the origins and evolution of these diseases. Our results show that the two cancers arose through similar processes and that both have striking signals of ongoing evolution. It is difficult to predict how this continued cancer evolution will impact devils.”
The researchers created an improved ‘reference genome’ – essentially a map of the entire DNA sequence – of the Tasmanian devil and compared this to DNA taken from 119 DFT1 and DFT2 tumours. DFT1 was first observed in 1996 in Tasmania’s northeast and is now widespread throughout Tasmania. DFT2, on the other hand, was first observed in 2014 and remains confined to a small area in Tasmania’s southeast. The scientists identified mutations in the tumours and used these to build ‘family trees’ of how the two cancers had each independently arisen and evolved over time.
By tracking mutations the researchers discovered that DFT2 acquired mutations about three times faster than DFT1. As mutations usually occur during cell division, the most likely explanation is that DFT2 is a faster growing cancer than DFT1, say the researchers, underlining the importance of DFT2 as a threat.
“DFT2 is still not widespread in the devil population, and very little is known about it. We were really startled to see just how quickly it was mutating, alerting us to what could be a very unpredictable threat to the devils in the long term,” said Maximilian Stammnitz, first author of the study.
The team found that DFT1 arose in the 1980s, up to 14 years before it was first observed, whereas DFT2 emerged between 2009 and 2012, only shortly before it was detected.
Mapping the mutations revealed that DFT1 underwent an explosive transmission event shortly after it emerged. This involved a single infected devil transmitting its tumour to at least six recipient devils.
DFT1 has now spread throughout almost the entire devil population and has recently been reported in the far northwest of Tasmania, one of the few remaining disease-free regions of the state.
Researchers also identified for the first time an instance of DFT1 transmission between a mother and the young in her pouch. Additionally, they found that the incubation period – the time between infection and the emergence of symptoms – can in some cases be a year or more. These findings have important implications for conservation scientists working to protect the species.
“I come from Tasmania and love Tasmanian devils – they have a special place in my heart,” said Murchison. “Transmissible cancers pose an unprecedented and unpredictable threat to Tasmanian devils. This research highlights the continuing importance of monitoring and conservation programmes. It also gives us new insights into the evolutionary mechanisms operating in cancer more broadly, including in human cancers.”
The research was funded by Wellcome, the Gates Cambridge Trust and Eric Guiler Tasmanian Devil Research Grants from the University of Tasmania Foundation.
Reference: M. R. Stammnitz et al. The evolution of two transmissible cancers in Tasmanian devils, Science, DOI: 10.1126/science.abq6453
Scientists have traced the family trees of two transmissible cancers that affect Tasmanian devils and have pinpointed mutations which may drive growth of deadly diseases.
animal healthGenomicsCancerMax StammnitzElizabeth MurchisonWellcome Sanger InstituteDepartment of Veterinary MedicineSchool of Biological SciencesSchool of the Biological SciencesTransmissible cancers pose an unprecedented and unpredictable threat to Tasmanian devils.Professor Elizabeth MurchisonMax StammnitzTasmanian Devil
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Minority ethnic doctors less likely to get specialty NHS training posts while some specialties show gender bias
Researchers from the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust examined data from applicants to Specialty Training Posts through Health Education England for the recruitment cycle 2021-22 to look at potential disparities in the success of applicants according to gender, ethnicity and disability.
During this period, there were just under 12,500 successful applicants to Health Education England for training posts – a success rate of one in three (32.7%). Overall, females were more successful than males (37.0% versus 29.1%).
The researchers found clear evidence that certain specialities were more attractive to females or to males. Of note, surgical specialities and radiology had the highest proportion of male applicants (65.3% and 64.3% respectively), while obstetrics and gynaecology and public health had the highest proportion of female applicants (72.4% and 67.2% respectively).
Senior author Professor Sharon Peacock, from the Department of Medicine at the University of Cambridge, said: “The success by female applicants in many specialties is a positive step towards gender balance, and perhaps reflects existing efforts to address disparities. But the skew in applications and subsequent recruitment by gender, particularly amongst surgical specialities, is concerning.”
Gender disparities are known to have knock-on effects. For example, a lack of female representation contributes towards a male dominated culture, which can then result in fewer female role models to inspire and encourage aspiring female doctors.
The researchers say there are several reasons for these disparities. In surgical specialities, for example, a male-dominated workplace culture, bullying and harassment, few female role models, and career inflexibility, have been suggested as factors that deter females from applying. Female surgeons have reported quality of life and fewer unsocial hours as explanations of why women prefer other clinical specialities, in addition to the fear that working less-than-full-time or taking career breaks is perceived negatively.
Approximately half (50.2%) of the applicants were non-UK graduates. The overall success rate of UK graduates was 44.5%, compared with 22.8% for non-UK graduates.
When it came to minority ethnic groups, after adjusting for country of graduation, applicants from eleven out of fifteen groups (73.3%) were significantly less likely to be successful compared to White British. Those who fared worst were those of Mixed White and Black African ethnicity, who were only half as likely (52%) to be successful as White British applicants.
Dr Dinesh Aggarwal, the study’s first author, also from the Department of Medicine, said: “The data suggests there’s a need to review recruitment policies and processes from a diversity and inclusion perspective. But the issues extend beyond recruitment – doctors from minority ethnic groups can struggle to progress within the NHS and report disproportionately high levels of discrimination from colleagues.
“More than four in ten of the medical and dental workforce in NHS trusts and clinical commissioning groups in England are from a minority ethnic group, and ensuring that they are able to work within an inclusive environment, that allows them to thrive and progress, should be a priority.”
Although only a very small proportion of successful applicants (1.4%) declared a disability, they were more likely to be successful (38.6% compared with 32.8% of non-disabled applicants). However, there were no disabled applicants to 22.4% of the specialities, and for a further 36.2% of specialities, no disabled applicants were accepted.
Dr Dinesh Aggarwal added: “It’s encouraging to see a high proportion of acceptances among individuals disclosing a disability. The NHS needs to ensure that application and recruitment processes are accessible and open to adjustments for all disabilities, eliminate any fear of discrimination, and provide assurance that all NHS workplaces will accommodate reasonable adjustments to ensure that disabled doctors can carry out their work. This will not only help to encourage more disabled applicants, but also allow disabled clinicians to feel more comfortable disclosing this information.”
Professor Peacock added: “The NHS is the largest employer in the UK and it’s vital that it nurtures diverse talent to benefit patient care. People from diverse backgrounds bring different lived experiences and perspectives, which in turn strengthens the pool of knowledge and skills within the NHS. A lack of workforce diversity can be detrimental to patient care, and research shows that inherent biases can influence how clinicians treat patients.”
Dr Aggarwal is a PhD student at Churchill College. Professor Peacock is a Fellow at St John’s College.
Reference
Aggarwal, D et al. Applications to medical and surgical specialist training in the UK National Health Service, 2021-22: a cross-sectional observational study to characterise the diversity of successful applicants. BMJ Open; 20 April 2023; DOI: 10.1136/bmjopen-2022-069846
Most minority ethnic groups are less successful than their White British counterparts when applying to specialty training programmes in the NHS, Cambridge researchers have shown. Their analysis, published today in BMJ Open, also found that while female applicants are more successful overall, particular specialities tend to appeal to different genders.
National Health Service (NHS)hospitalsgenderethnicityDinesh AggarwalSharon PeacockCambridge University Hospitals NHS Foundation TrustSchool of Clinical MedicineDepartment of MedicineThe NHS is the largest employer in the UK and it’s vital that it nurtures diverse talent to benefit patient careSharon PeacockDarkoStojanovicDoctor's white coat with stethoscope and pens
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Sleight-of-hand magic trick only fools monkeys with opposable thumbs
By performing a famous magic trick for three species of monkey with differing hand structures, scientists have discovered that – in order to deceive – a conjuror needs the same anatomy as their audience.
Psychologists used a sleight-of-hand trick called the French drop, in which an object appears to vanish when a spectator assumes it is taken from one hand by the hidden thumb of the other hand.
The study, carried out at the University of Cambridge’s Comparative Cognition Lab, found that monkeys lacking opposable thumbs did not fall for the assumption – staying wise to the whereabouts of tasty treats a magician tried to disappear.
The research suggest that sharing a biomechanical ability may be necessary for accurately anticipating the movements of those same limbs in other individuals.
This is true even when those apparently accurate predictions end in befuddlement at the hands of an illusionist. The study is published today in the journal Current Biology.
“Magicians use intricate techniques to mislead the observer into experiencing the impossible. It is a great way to study blind spots in attention and perception,” said Dr Elias Garcia-Pelegrin, who has practiced magic for a decade, and conducted the experimental work during his PhD at Cambridge.
“By investigating how species of primates experience magic, we can understand more about the evolutionary roots of cognitive shortcomings that leave us exposed to the cunning of magicians.”
“In this case, whether having the manual capability to produce an action, such as holding an item between finger and thumb, is necessary for predicting the effects of that action in others,” said Garcia-Pelegrin, recently appointed an assistant professor at the National University of Singapore.
The French drop is often the first trick any budding magician sets out to master.
A coin is displayed in one hand. The other hand reaches over and grabs it. The palm of the second hand faces inwards, with the magician’s thumb concealed behind fingers.
The audience knows the thumb is lurking – ready to grip – so assumes the coin has been taken when it is no longer visible. Their attention follows the second hand, only to find it empty at “the reveal”. The magician had secretly dropped the coin into the palm of the original hand.
Food morsels replaced coins for the monkeys, and were given as rewards – but only if the animals guessed the correct hand. Scientists predicted that monkeys with opposable thumbs would act like human audiences: assume the hidden thumb had grabbed the item, and choose the wrong hand.
They repeatedly performed the French drop on 24 monkeys. Eight capuchins were dazzled with peanuts, eight squirrel monkeys with dried mealworms, and eight marmosets with marshmallows.
Capuchins are famed for dexterity, and use stone tools to crack nuts in the wild. They can waggle each finger, and have opposable thumbs allowing “precision grip” between thumb and forefingers.
The capuchins were regularly fooled by the French drop (81% of the time). They mostly chose the empty second hand, and experienced a paucity of peanuts as a result.
Squirrel monkeys are much less dextrous than capuchins, with limited thumb rotation, but can oppose their thumbs. As such, they are still familiar with a hidden thumb interacting with fingers. However, they cannot perform a ‘precision grip’ in the same way as capuchins and humans.
Yet squirrel monkeys were routinely misled by vanishing mealworms (93% of the time). “Squirrel monkeys cannot do full precision grips, but they were still fooled. This suggests that a monkey doesn’t have to be expert in a movement in order to predict it, just roughly able to do it,” said Garcia-Pelegrin.
Marmosets do not have opposable thumbs. Their thumbs align with their fingers to make five equidistant digits, ideal for climbing thick tree trunks. Marmosets were rarely taken in by magic (just 6% of the time). They simply chose the hand in which the marshmallow was initially placed, and stuck with it.
Previous work from the Cambridge team shows that species without hands at all, in this case birds from the corvid family, namely Eurasian jays, make similar choices as marmosets when confronted with the French drop.
The team also tried nullifying the tricks by actually completing the hand-to-hand transfers, instead of misdirecting with a French drop. This time, the capuchins and squirrel monkeys anticipated correctly and dined out, and the marmosets missed out.
Finally, the scientists devised their own version of the French drop, which they call the “Power drop”. It utilises a hand action that all the monkey species can perform – essentially a full fist grab. The power drop fooled all of the monkey species the vast majority of the time.
“There is increasing evidence that the same parts of the nervous system used when we perform an action are also activated when we watch that action performed by others,” said Prof Nicola Clayton FRS, senior author of the study from Cambridge’s Department of Psychology.
“This mirroring in our neural motor system might explain why the French drop worked for the capuchins and squirrel monkeys but not for marmosets.”
“It’s about the embodiment of knowledge,” added Clayton. “How one’s fingers and thumbs move helps to shape the way we think, and the assumptions we make about the world – as well as what others might see, remember and anticipate, based on their expectations.”
“Our work raises the intriguing possibility that an individual’s inherent physical capability heavily influences their perception, their memory of what they think they saw, and their ability to predict manual movements of those around them.”
Another co-author of the study, Clive Wilkins, Artist in Residence at Cambridge’s Department of Psychology, is a professional magician and Member of the Magic Circle.
Illusion involving a hidden thumb confounds capuchin and squirrel monkeys for the same reason as humans – it misdirects the expected outcomes of actions they can carry out.
animal behaviourPsychologycomparative cognitioncognitionNicola ClaytonElias Garcia-PelegrinNational University of SingaporeDepartment of PsychologySchool of the Biological SciencesThis mirroring in our neural motor system might explain why the French drop worked for the capuchins and squirrel monkeys but not for marmosetsNicola Clayton Not all monkeys are fooled by magic. Elias Garcia-PelegrinA Humboldt's squirrel monkey is fooled by a French Drop as part of the experiment.
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Increasing availability of non-alcoholic drinks may reduce amount of alcohol purchased online
The team used a simulated supermarket that presented shoppers with varying proportions of alcoholic and non-alcoholic drinks and asked them to select drinks to purchase for their next online shop. They found that shoppers who were exposed to more non-alcoholic drinks selected and purchased fewer units of alcohol. The findings are published in PLOS Medicine.
Excessive alcohol consumption is a major risk factor for a number of diseases, including cancer, heart disease and stroke. Encouraging people to change their behaviour could therefore have significant health benefits at both an individual and population level.
There is increasing evidence that people can be ‘nudged’ towards reducing their alcohol consumption by making small adjustments to their environment. For example, scientists at Cambridge’s Behaviour and Health Research Unit have previously shown that serving wine in smaller glasses – even while keeping the amount of wine in the glasses the same – led to people consuming less alcohol.
A recent analysis found that reducing the proportion of unhealthy snacks available can reduce how much of these food products people consume, though the evidence included was limited in both quality and quantity. The Cambridge team wanted to see if a similar approach might work to nudge people towards consuming fewer alcoholic drinks.
The researchers recruited 737 adults living in England and Wales, all of whom regularly purchased alcohol online, to take part in the study. Of these, just over 600 completed the study and were included in the final analysis – 60% were female and the average (mean) age was 38.
Participants selected drinks from 64 options in a simulated online supermarket designed to look and function like a real online supermarket. Options included a range of beers, ciders, alcohol-free beer and cider alternatives, and soft drinks.
Participants were randomly assigned to one of three groups, each of which was presented with a different proportion of alcoholic and non-alcoholic drinks. 25% of the drinks seen by Group 1 were non-alcoholic. For Group 2, this increased to 50%, and for Group 3 the proportion of non-alcoholic drinks seen rose to 75%.
Those exposed to the highest proportion of non-alcoholic drinks (Group 3) selected fewer alcohol units, 17.5 units, compared to 29.4 units in those exposed to the lowest proportion of non-alcoholic drinks (Group 1) – equivalent to a reduction of about 41%.
Participants were then asked to actually purchase the same drinks in an online supermarket, Tesco, the largest national supermarket in the UK. Around two-thirds of participants completed this second stage, with 422 participants going on to purchase drinks. The researchers point out that ‘cart abandonment’ – where people do not purchase items they put in their shopping cart – is common in online shopping contexts.
The researchers found that amongst participants exposed to the highest proportion of non-alcoholic drinks, 52% of the drinks purchased were alcoholic, compared to 70% of drinks that were purchased by those exposed to the lowest proportion of non-alcoholic drinks.
Lead author Dr Natasha Clarke said: “We created our simulated supermarket to be as close as possible to an actual online supermarket and found that increasing the proportion of non-alcoholic drinks that shoppers were exposed to made a meaningful difference to their alcohol selection. Though we’d need to confirm these findings using only a real online supermarket, they are very promising.”
While the current market for alcohol-free beer, wine and spirits represents only a small share of the global alcohol industry, it is rapidly growing. For example, low and no-alcohol beer currently accounts for 3% of the total beer market, but this is forecast to increase by nearly 13% per year over the next 3 years and is the fastest growing drinks segment in the UK.
Senior author Dr Gareth Hollands said: “Supermarkets typically stock a wider range of alcoholic drinks than non-alcoholic alternatives aimed at adults, but this is slowly changing. Our results suggest that if non-alcoholic options were to become the majority instead, we might expect to see substantial reductions in alcohol purchasing.”
Importantly, the overall number of drinks that participants selected and purchased remained similar between groups, suggesting that effects were a result of shifting people’s choices. This implies overall drink sales and potentially revenues may be relatively unchanged, dependent on the pricing of non-alcoholic drinks.
Professor Dame Theresa Marteau, Director of the Behaviour and Health Research Unit and a Bye-Fellow at Christ's College, said: “We all know that drinking too much alcohol is bad for us, but we’re often unaware of how much we are influenced by the environment around us. Making changes to this environment – from exposing people to a greater proportion of healthier options through to changing the sizes of the utensils we eat and drink from – can help us cut down on potentially unhealthy habits. Even relatively small changes can make a difference both to individuals and at a population level.”
Although some of the non-alcoholic drink options in the current study contained no sugar and were generally lower in calories than the alcoholic options – an average of 64 calories per non-alcoholic drink versus 233 calories per alcoholic drink – many soft drinks and alcohol-free alternatives still contain large amounts of sugar and calories. The researchers argue that, given the health risks associated with sugary drink consumption, continued regulation and policies to reduce sugar content and consumption from both alcoholic and non-alcoholic drinks is needed to mitigate these risks.
The research was funded by Wellcome and carried out at the Behaviour and Health Research Unit, University of Cambridge. Dr Clarke is now a Lecturer in Psychology at Bath Spa University. Dr Hollands is a Principal Research Fellow at UCL.
Reference
Clarke, N et al. Impact on alcohol selection and online purchasing of changing the proportion of available non-alcoholic versus alcoholic drinks: A randomised controlled trial. PLOS Med; 30 Mar 2023; DOI: 10.1371/journal.pmed.1004193
Increasing the proportion of non-alcoholic drinks on sale in online supermarkets could reduce the amount of alcohol people purchase, suggests a study published today led by researchers at the University of Cambridge.
Spotlight on public healthalcoholTheresa MarteauGareth HollandsNatasha ClarkeWellcomeSchool of Clinical MedicineDepartment of Public Health and Primary CareCambridge Public HealthBehaviour and Health Research Unit (BHRU)Christ's CollegeWe all know that drinking too much alcohol is bad for us, but we’re often unaware of how much we are influenced by the environment around usTheresa Marteauaire images (Getty Images)Hand holding a smartphone inside a cafeteria with an app to buy in the supermarket
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Cell mapping and ‘mini placentas’ give new insights into human pregnancy
Researchers from the University of Cambridge, the Wellcome Sanger Institute, the Friedrich Miescher Institute for Biomedical Research (FMI), Switzerland, EMBL’s European Bioinformatics Institute (EMBL-EBI), and collaborators, have created an in-depth picture of how the placenta develops and communicates with the uterus.
The study, published today in the journal Nature, is part of the Human Cell Atlas initiative to map every cell type in the human body. It informs and enables the development of experimental models of the human placenta.
"For the first time, we have been able to draw the full picture of how the placenta develops and describe in detail the cells involved in each of the crucial steps. This new level of insight can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide,” said Anna Arutyunyan, co-first author at the University of Cambridge and Wellcome Sanger Institute.
The placenta is a temporary organ built by the foetus that facilitates vital functions such as foetal nutrition, oxygen and gas exchange, and protects against infections.The formation and embedding of the placenta into the uterus, known as placentation, is crucial for a successful pregnancy.
Understanding normal and disordered placentation at a molecular level can help answer questions about poorly understood disorders including miscarriage, stillbirth, and pre-eclampsia. In the UK, mild pre-eclampsia affects up to six per cent of pregnancies. Severe cases are rarer, developing in about one to two per cent of pregnancies.
Many of the processes in pregnancy are not fully understood, despite pregnancy disorders causing illness and death worldwide. This is partly due to the process of placentation being difficult to study in humans, and while animal studies are useful, they have limitations due to physiological differences.
During its development, the placenta forms tree-like structures that attach to the uterus, and the outer layer of cells, called trophoblast, migrate through the uterine wall, transforming the maternal blood vessels to establish a supply line for oxygen and nutrients.
In the new study, scientists built on previous work investigating the early stages of pregnancy, to capture the process of placental development in unprecedented detail. Cutting-edge genomic techniques allowed them to see all of the cell types involved and how trophoblast cells communicate with the maternal uterine environment around them.
The team uncovered the full trajectory of trophoblast development, suggesting what could go wrong in disease and describing the involvement of multiple populations of cells, such as maternal immune and vascular cells.
"This research is unique as it was possible to use rare historical samples that encompassed all the stages of placentation occurring deep inside the uterus. We are glad to have created this open-access cell atlas to ensure that the scientific community can use our research to inform future studies,” said Professor Ashley Moffett, co-senior author at the University of Cambridge's Department of Pathology.
They also compared these results to placental trophoblast organoids, sometimes called ‘mini-placentas’, that are grown in the lab. They found that most of the cells identified in the tissue samples can be seen in these organoid models. Some later populations of trophoblast are not seen and are likely to form in the uterus only after receiving signals from maternal cells.
The team focussed on the role of one understudied population of maternal immune cells known as macrophages. They also discovered that other maternal uterine cells release communication signals that regulate placental growth.
The insights from this research can start to piece together the unknowns about this stage of pregnancy. The new understanding will help in the development of effective lab models to study placental development and facilitate new ways to diagnose, prevent, and treat pregnancy disorders.
This research was funded by Wellcome, The Royal Society, and the European Research Council.
Reference
Arutyunyan, A. et al: 'Spatial multiomics map of trophoblast development in early pregnancy.' March 2023, Nature. DOI: 10.1038/s41586-023-05869-0
Adapted from a press release by the Wellcome Sanger Institute.
Researchers have mapped the complete trajectory of placental development, helping shed new light on why pregnancy disorders happen.
ReproductionAshley MoffettAnna ArutyunyanWellcome Sanger InstituteThe Friedrich Miescher Institute for Biomedical ResearchEuropean Bioinformatics InstituteDepartment of PathologyCambridge Reproduction Strategic Research InitiativeSchool of the Biological SciencesThis can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide.Anna ArutyunyanKenny Roberts, Wellcome Sanger InstituteCells of the placenta
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Finding new ways to diagnose childhood brain tumours
Funded by The Brain Tumour Charity, this research aims to develop new ways to diagnose medulloblastoma using minimally invasive methods, protecting the quality of life of children with this diagnosis.
Medulloblastoma is the most common cancerous childhood brain tumours, accounting for 15-20% of all childhood brain tumour diagnoses. Around 52 children are diagnosed with a medulloblastoma each year in the UK. These tumours are fast growing and develop at the back of the brain in the cerebellum.
Dr Jessica Taylor, a postdoctoral researcher at the University of Cambridge working in Professor Richard Gilbertson’s lab at the Cancer Research UK Cambridge Institute, will focus on one of the four subtypes of medulloblastoma - wingless (WNT) medulloblastoma. WNT-medulloblastoma is typically difficult to operate on, but is highly curable with chemotherapy and radiation.
The research will use antibodies that have been designed to bind to the WNT-medulloblastoma cells. Once bound to the cells, they will be visible on a PET scan and can be used to diagnose this subtype of medulloblastoma. This method avoids the use of invasive surgery and so will protect children from the potential long-term, damaging effects of surgery such as memory problems and speech issues.
Dr Taylor, the recipient of a Future Leaders Award from The Brain Tumour Charity, said: “With one in four children with this tumour type suffering long-term memory loss and speech issues after surgery, it is important that we work towards improving diagnostic methods which avoid surgery.
“I hope my research will change the way medulloblastoma is clinically diagnosed and that it will improve the treatment and quality of life for children diagnosed with this disease.”
The antibodies will be designed to bind to drugs that could treat WNT-medulloblastoma. This innovative approach would deliver treatments directly to the tumour, potentially replacing the need for more traditional chemotherapy. This could have several benefits including giving patients an additional treatment option and offering a more targeted therapy, potentially reducing the side effects from treatment.
Dr David Jenkinson, Chief Scientific Officer at The Brain Tumour Charity, said: “This innovative project exploits the features of WNT-medulloblastoma to create specific antibodies that will help diagnose and even treat this type of tumour, avoiding unnecessary surgery for the children diagnosed. Focusing research on non-invasive diagnostics and treatments helps to prevent long-term damage that can result from surgery.”
Adapted from a press release from The Brain Tumour Charity
Cambridge researchers are using new techniques to distinguish different types of medulloblastoma, a type of brain tumour in children.
Cancerbrain tumoursspotlight on future therapeuticsJessica TaylorThe Brain Tumour CharitySchool of Clinical MedicineCambridge Cancer CentreCancer Research UK Cambridge InstituteWith one in four children with this tumour type suffering long-term memory loss and speech issues after surgery, it is important that we work towards improving diagnostic methods which avoid surgeryJessica TaylorCRUK Cambridge InstituteDr Jessica TaylorSophie Harper's storyJohn Huggins’ granddaughter Sophie Harper was diagnosed with medulloblastoma in 2006.
John said: “Until the age of nineteen months Sophie seemed to be a normally developing little girl, she walked at eleven months and her speech was well ahead of her age. From nineteen months she started to vomit regularly and when her mother took her to the doctors on day four, he diagnosed a virus. After ten days my daughter returned to the doctor, but again he said it was a virus. Sophie was taken to the doctor a number of times over the next two and a half months and there was no change with the doctor’s diagnosis. Sophie then started to lose her ability to walk, no longer was she the happy child she was, complaining of head pain, started falling over regularly and wanting to be carried around. It was only then the doctor agreed for Sophie to have a scan.”
Sophie’s scan took place at Norwich University Hospital and revealed a mass on her cerebellum. She was transferred to Addenbrooke’s Hospital, Cambridge, for further tests and a medulloblastoma tumour was confirmed.
John said: “None of us had any knowledge of brain tumours and it became a huge learning curve. At that point Mum and Dad had to decide whether to take the option of curative or palliative care. Sophie always had a big personality and was such a fighter with any illness, so Mum and Dad decided they had to give her the tools to fight with and take the curative option”.
The following week, Sophie underwent an operation to try and remove the tumour and the family waited anxiously in the garden of Addenbrooke’s Hospital for news. The operation was expected to last around three to four hours but Sophie was in surgery for seven and a half.
John said: “Sophie didn’t regain consciousness for thirty two days, due to the insult to her brain. She spent three months in intensive care and was now needing an oxygen supplement and having to be fed through a gastrostomy tube. Both of these would stay for the next six years of her life.
“It also became clear that there were other side effects from the operation: her speech was significantly impacted and she was unable to hold our gaze and her movements were uncoordinated and clumsy. During the time of her treatment she received more than a hundred transfusions of blood products due to low blood cell counts, but none of us can remember a single day, when she didn’t make us laugh or brighten our day. She had an amazing ability to do that.
“It is true to say, surgery had a dramatic effect on Sophie, she was no longer the child we knew before the operation.”
Just before Sophie’s eighth birthday, her family were devastated when a scan revealed another growth on her brain. She was given three months to live, but survived almost a year and sadly died shortly before her ninth birthday in 2013.
After her death, Sophie’s family set up The Sophie Elin Harper Fund with The Brain Tumour Charity to raise funds and awareness of brain tumours. Their fundraising to date totals a remarkable £38,000.
John said: “The side effects Sophie had following surgery, with the insult to her brain, were huge and totally life changing.
“Sophie lived a very cruel life, in and out of hospital. Even the shunt fitted in her brain had to be replaced on three occasions. She never regained the ability to walk, and was always fed through a gastrostomy tube, together with an oxygen supplement, but she never complained.
“The possibility of avoiding side effects and unnecessary surgery would be a real turning point in the treatment of medulloblastoma.”
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