Updated: 49 min 11 sec ago
‘Exhausted’ immune cells in healthy women could be target for breast cancer prevention
Everyone has BRCA1 and BRCA2 genes, but mutations in these genes - which can be inherited - increase the risk of breast and ovarian cancer.
The study found that the immune cells in breast tissue of healthy women carrying BRCA1 or BRCA2 gene mutations show signs of malfunction known as ‘exhaustion’. This suggests that the immune cells can’t clear out damaged breast cells, which can eventually develop into breast cancer.
This is the first time that ‘exhausted’ immune cells have been reported in non-cancerous breast tissues at such scale - normally these cells are only found in late-stage tumours.
The results raise the possibility of using existing immunotherapy drugs as early intervention to prevent breast cancer developing, in carriers of BRCA1 and BRCA2 gene mutations.
The researchers have received a ‘Biology to Prevention Award’ from Cancer Research UK to trial this preventative approach in mice. If effective, this will pave the way to a pilot clinical trial in women carrying BRCA gene mutations.
“Our results suggest that in carriers of BRCA mutations, the immune system is failing to kill off damaged breast cells - which in turn seem to be working to keep these immune cells at bay,” said Professor Walid Khaled in the University of Cambridge’s Department of Pharmacology and Wellcome-MRC Cambridge Stem Cell Institute, senior author of the report.
He added: “We’re very excited about this discovery, because it opens up potential for a preventative treatment other than surgery for carriers of BRCA breast cancer gene mutations.
“Drugs already exist that can overcome this block in immune cell function, but so far, they’ve only been approved for late-stage disease. No-one has really considered using them in a preventative way before.”
The results are published today in the journal Nature Genetics.
Risk-reducing surgery, in which the breasts are removed, is offered to those at increased risk of breast cancer. This can be a difficult decision for young women to make and can have a significant effect on body image and sexual relationships.
“The best way to prevent breast cancer is to really understand how it develops in the first place. Then we can identify these early changes and intervene,” said Khaled.
He added: “Late-stage breast cancer tends to be very unpredictable and hard to manage. As we make better and better drugs, the tumours just seem to find a way around it.”
Using samples of healthy breast tissue collected from 55 women across a range of ages, the researchers catalogued over 800,000 cells - including all the different types of breast cell.
The resulting Human Breast Cell Atlas is now available as a resource for other researchers to use and add to. It contains huge amounts of information on other risk factors for breast cancer including Body Mass Index (BMI), menopausal status, contraceptive use and alcohol consumption.
“We've found that there are multiple breast cell types that change with pregnancy, and with age, and it’s the combination of these effects - and others - that drives the overall risk of breast cancer,” said Austin Reed, a PhD student in the University of Cambridge’s Department of Pharmacology and joint first author of the report.
He added: “As we collect more of this type of information from samples around the world, we can learn more about how breast cancer develops and the impact of different risk factors - with the aim of improving treatment.”
One of the biggest challenges in treating breast cancer is that it is not just one disease, but many. Many different genetic variations can lead to breast cancer, and genetic risk interacts with other risk factors in complicated ways.
For example, it is known that the likelihood of breast cancer increases with age, but this risk is greatly reduced by pregnancy early in life. And age-associated risk is greatly increased in carriers of the breast cancer genes BRCA1 and BRCA2.
The new study aimed to understand how some of these risk factors interact, by characterising the different cell types in the human breast under many different physiological states.
The researchers used a technique called ‘single cell RNA-sequencing’ to characterise the many different breast cell types and states. Almost all cells in the body have the same set of genes, but only a subset of these are switched on in each cell – and these determine the cell’s identity and function. Single cell RNA-sequencing reveals which genes are switched on in individual cells.
“Breast cancer occurs around the world, but social inequalities mean not everyone has access to treatment. Prevention is the most cost-effective approach. It not only tackles inequality, which mostly affects low-income countries, but also improves disease outcome in high-income countries,” said Dr Sara Pensa, Senior Research Associate in the University of Cambridge’s Department of Pharmacology and joint first author of the study.
Breast tissue samples were provided by the Breast Cancer Now tissue bank.
The research was primarily funded by the Medical Research Council and Cancer Research UK.
Reference: Reed, A.D. et al: ‘A human breast cell atlas enables mapping of homeostatic cellular shifts in the adult breast.’ Nature Genetics, March 2024. DOI: 10.1038/s41588-024-01688-9
Researchers at the University of Cambridge have created the world’s largest catalogue of human breast cells, which has revealed early cell changes in healthy carriers of BRCA1 and BRCA2 gene mutations.
breast cancerCancerWalid KhaledSara PensaAustin ReedBreast Cancer NowDepartment of PharmacologyWellcome-MRC Cambridge Stem Cell InstituteCRUK Cambridge InstituteMagdalene CollegeSchool of the Biological SciencesWe’re very excited about this discovery, because it opens up potential for a preventative treatment other than surgery for carriers of BRCA breast cancer gene mutations.Walid KhaledAngiola Harry on UnsplashWoman holds pink breast cancer awareness ribbon. Credit angiola-harry-unsplash
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Clinical trial underway to treat ultra-rare genetic disease with possible link to leader of mutiny on the Bounty
A clinical trial to look at repurposing the UK-licensed medicine deferiprone for patients with the ultra-rare genetic disease neuroferritinopathy has launched today at the University of Cambridge.
Neuroferritinopathy is a progressive and incurable brain disorder caused by changes in a gene that produces a specific protein - ferritin light chain protein. This change leads to the build-up of iron in the brain. The disease usually appears in middle-aged adults and causes severe symptoms that impact on day-to-day life, eventually resulting in the loss of speech and swallowing. There are currently no effective treatments.
Funded by LifeArc, the new randomised placebo-controlled trial - DefINe - will be led by Professor Patrick Chinnery from the Department of Clinical Neurosciences. It aims to stop the progression of the disease by reducing the iron accumulation in the brain with an existing drug called deferiprone. Deferiprone is an affordable oral tablet that is already licensed for use in the UK to reduce iron levels in blood conditions like thalassemia. If successful, the trial could also open the possibility of deferiprone being used for other neurodegenerative conditions linked with build-up of iron the brain.
Professor Chinnery said: “Neuroferritinopathy leads to severe disability and currently has no cure. The DefINe trial will show whether we can stop the disease in its tracks by pulling iron out of the brain using a well-known medicine called deferiprone.
“By funding this study, LifeArc has given the first hope of a treatment for affected families. If successful, the trial will open the possibility of using a similar approach for other neurodegenerative conditions linked to the build-up of iron in the brain, including Parkinson’s disease.”
Neuroferritinopathy affects approximately 100 patients worldwide. Initial discovery of the condition came when a surprising number of individuals diagnosed found to live in the Lake District in Cumbria experienced similar symptoms with a series of incorrect diagnoses. Research into the ancestry of these families by Professor John Burn, a clinical geneticist at Newcastle Hospitals NHS Foundation Trust, discovered the genetic commonality and also found an interesting potential link to the past.
Professor Burn found that a rare mutation caused the progression of the condition and almost all the known cases were likely to be descended from the same ancestor. He traced it back to the 18th Century in Cockermouth in Cumbria and families with the surname Fletcher. Professor Burn suggested they could have shared common ancestry with Fletcher Christian (Fletcher being his surname), known for leading the mutiny on the Bounty in April 1789, given he was also from the region.
The DefINe trial will involve 40 patients taking the drug for a year, who will undergo state-of-the-art 7T magnetic resonance imaging (MRI) scanning to monitor the iron levels in the brain throughout. The evidence collected will form the basis of an application for licensing in the UK under ‘Exceptional Circumstances’, which is often used for rare conditions where the number of people affected is low. This means, if the trial is successful the drug could go on to benefit all people with the condition more quickly.
Samantha Denison, a patient hoping to participate in the trial, said: “It came as such a surprise to be informed of the trial and to learn that we have not been forgotten about. To have the chance to be involved in the trial gives me such hope. If it can help to slow or stop the condition progressing, that would be a huge relief. Just to know that by taking part we could also be helping future generations, is amazing.”
LifeArc has contributed £750,000 to the project and Lipomed, a Swiss life sciences company, has offered to provide both a cost-effective generic form of deferiprone, Deferiprone Lipomed, and a placebo to the trial – a Gift in Kind worth £250,000.
Dr Catriona Crombie, Head of LifeArc’s Rare Disease Translational Challenge, said: “Drug repurposing trials like this are an increasingly effective way of taking treatments that have already been approved and applying them to new conditions and diseases. This will help unlock new treatments for conditions that currently have few, if any, available."
Dr Chantal Manz, Chief Scientific Officer Lipomed AG, Switzerland, said: “Lipomed is very excited to support this promising study concept in patients with neuroferritinopathy, by providing deferiprone 500 mg film-coated tablets and matching placebo tablets. We recognise the unmet clinical need and the potentially significant benefit of this orally active iron chelator. Deferiprone is able to penetrate the blood-brain barrier and may reduce cerebral iron accumulation in patients with this extremely rare, but devastating genetic neurodegenerative disorder, for which no alternative treatments are available.”
Adapted from a press release by LifeArc.
neurodegenerationPatrick ChinneryNewcastle Hospitals NHS Foundation TrustLifeArcLipomed AGDepartment of Clinical NeurosciencesSchool of Clinical MedicineCambridge NeuroscienceIf successful, the trial will open the possibility of using a similar approach for other neurodegenerative conditions linked to the build-up of iron in the brain, including Parkinson’s disease.Patrick Chinnery Patrick Chinnery looks at brain scans
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Fish fed to farmed salmon should be part of our diet, too, study suggests
Scientists found that farmed salmon production leads to an overall loss of essential dietary nutrients. They say that eating more wild ‘feed’ species directly could benefit our health while reducing aquaculture demand for finite marine resources.
Researchers analysed the flow of nutrients from the edible species of wild fish used as feed, to the farmed salmon they were fed to. They found a decrease in six out of nine nutrients in the salmon fillet – calcium, iodine, iron, omega-3, vitamin B12 and vitamin A, but increased levels of selenium and zinc.
Most wild ‘feed’ fish met dietary nutrient recommendations at smaller portion sizes than farmed Atlantic salmon, including omega-3 fatty acids which are known to reduce the risk of cardiovascular disease and stroke.
“What we’re seeing is that most species of wild fish used as feed have a similar or greater density and range of micronutrients than farmed salmon fillets,” said lead author, Dr David Willer, Zoology Department, University of Cambridge.
“Whilst still enjoying eating salmon and supporting sustainable growth in the sector, people should consider eating a greater and wider variety of wild fish species like sardines, mackerel and anchovies, to get more essential nutrients straight to their plate.”
In the UK, 71% of adults have insufficient vitamin D in winter, and teenage girls and women often have deficiencies of iodine, selenium and iron. Yet while, 24% of adults ate salmon weekly, only 5.4% ate mackerel, 1% anchovies and just 0.4% herring.
“Making a few small changes to our diet around the type of fish that we eat can go a long way to changing some of these deficiencies and increasing the health of both our population and planet,” said Willer.
The researchers found consuming one-third of current food-grade wild feed fish directly would be the most efficient way of maximising nutrients from the sea.
“Marine fisheries are important local and global food systems, but large catches are being diverted towards farm feeds. Prioritising nutritious seafood for people can help improve both diets and ocean sustainability,” said senior author Dr James Robinson, Lancaster University.
This approach could help address global nutrient deficiencies say the team of scientists from the University of Cambridge, Lancaster University, University of Stirling and the University of Aberdeen.
The study was published today in the journal, Nature Food.
The scientists calculated the balance of nutrients in edible portions of whole wild fish, used within pelleted salmon feed in Norway, compared to the farmed salmon fillets.
They focused on nine nutrients that are essential in human diets and concentrated in seafood – iodine, calcium, iron, vitamin B12, vitamin A, omega-3 (EPA + DHA), vitamin D, zinc and selenium.
The wild fish studied included Pacific and Peruvian anchoveta, and Atlantic herring, mackerel, sprat and blue whiting – which are all marketed and consumed as seafood.
They found that these six feed species contained a greater, or similar, concentration of nutrients as the farmed salmon fillets. Quantities of calcium were over five times higher in wild feed fish fillets than salmon fillets, iodine was four times higher, and iron, omega-3, vitamin B12, and vitamin A were over 1.5 times higher.
Wild feed species and salmon had comparable quantities of vitamin D.
Zinc and selenium were found to be higher in salmon than the wild feed species – the researchers say these extra quantities are due to other salmon feed ingredients and are a real mark of progress in the salmon sector.
“Farmed salmon is an excellent source of nutrition, and is one of the best converters of feed of any farmed animal, but for the industry to grow it needs to become better at retaining key nutrients that it is fed. This can be done through more strategic use of feed ingredients, including from fishery by-products and sustainably-sourced, industrial-grade fish such as sand eels”, said Dr Richard Newton of the Institute of Aquaculture, University of Stirling, whose team also included Professor Dave Little, Dr Wesley Malcorps and Björn Kok.
“It was interesting to see that we’re effectively wasting around 80% of the calcium and iodine from the feed fish – especially when we consider that women and teenage girls are often not getting enough of these nutrients”.
Willer said “These numbers have been underacknowledged by the aquaculture industry’s standard model of quoting Fish In Fish Out (FIFO) ratios rather than looking at nutrients.
The researchers would like to see a nutrient retention metric adopted by the fishing and aquaculture industries. They believe that if combined with the current FIFO ratio, the industry could become more efficient, and reduce the burden on fish stocks that also provide seafood. The team are building a standardised and robust vehicle for integrating the nutrient retention metric into industry practice.
“We’d like to see the industry expand but not at a cost to our oceans,” said Willer.
“We’d also like to see a greater variety of affordable, convenient and appealing products made of wild ‘feed’ fish and fish and salmon by-products for direct human consumption.”
The research was funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS), a Royal Society University Research Fellowship, a Leverhulme Trust Early Career Fellowship a Henslow Fellowship at Murray Edwards College and the University of Cambridge.
Reference: D. Willer et al. Wild fish consumption can balance nutrient retention in farmed fish Nature Food DOI: 10.1038/s43016-024-00932-z
The public are being encouraged to eat more wild fish, such as mackerel, anchovies and herring, which are often used within farmed salmon feeds. These oily fish contain essential nutrients including calcium, B12 and omega-3 but some are lost from our diets when we just eat the salmon fillet.
sustainabilityfishingGlobal food securityDavid WillerZoology DepartmentSchool of the Biological SciencesMaking a few small changes to our diet around the type of fish that we eat can go a long way to changing some of these deficiencies and increasing the health of both our population and planet Dr David Willer, Zoology DepartmentJoff Lee / The Image Bank / Getty Mackerel with potato salad
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AI predicts healthiness of food menus
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AI predicts healthiness of food menus
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AI predicts healthiness of food menus
Study highlights ‘double burden’ of unhealthy food environment in deprived areas
By Craig Brierley
Published 8 March 2024
Cambridge researchers have used artificial intelligence to predict the healthiness of café, takeaway and restaurant menus at outlets across Britain and used this information to map which of its local authorities have the most and least healthy food environments.The findings, published in Health & Place, highlight the double burden faced by people living in the most deprived areas, where there tend to be more food outlets per capita – more than double the number in the least deprived areas – and these outlets tend to be less healthy.
‘Out-of-home’ food – whether that’s food eaten in a pub, café or restaurant or takeaway food – is an increasing part of how many people eat. But this food tends to be higher in calories, saturated fat and salt and less nutritious than food prepared at home.
Studies have shown consistently that the more an individual eats food out of home – especially fast food – the poorer the quality of their diet and the higher their body weight. In the UK, there also tend to be more fast food outlets in more deprived neighbourhoods.
Not all menus are equal, however – some will be healthier than others – but little is known about whether there are differences between neighbourhoods in the healthiness of out-of-home food outlets.
“Given the link between the food environment and diet, it’s important to understand how healthy this environment is at a local level. This will empower local authorities to take action to try and improve the consumer food environment.”Yuru Huang, a Gates Cambridge Scholar at the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge
To explore this, Huang and colleagues examined menus from almost 55,000 food outlets on Just Eat, an online food ordering and delivery platform. Each outlet’s menu was given a healthiness score of 0-12 (with 12 being the healthiest) based on a number of factors including: the number of special offers (such as meal deals or family meals), desserts, salads, chips, milk, water, and the diversity of vegetables.
As not every food outlet is on Just Eat, the team turned to an artificially-intelligent ‘deep learning’ model, trained on a subset of Just Eat data, to predict menu healthiness of every out-of-home food outlet in Britain – a total of almost 180,000 outlets. These outlets were classified into four categories:
- cafés, snack bars, and tea rooms
- fast food and takeaways
- pubs, bars, and inns
- restaurants
The only information available for all out-of-home food outlets were the outlets’ names and hygiene ratings. When the team tested their model, they found that the outlet’s name was the best at predicting the healthiness of its menu.
While the complexities of menu healthiness cannot be accurately captured by name only, the researchers validated their results against a different set of test data from Just Eat to that used in the model training, and against real menus from outlets in Cambridge and Peterborough to demonstrate that the model works.
Restaurants were found, on average, to have the healthiest menus, followed by: cafes, snack bars, and tea rooms; pubs, bars, and inns; and lastly fast food and takeaways.
The team used geographical data to map the food outlets, summarising the average menu healthiness of all out-of-home food outlets at the local authority level. Local authority districts with the highest menu healthiness scores included City of London, Kensington and Chelsea, and Westminster. The local authority districts with the lowest menu healthiness scores were Northeast Lincolnshire, Luton, and Kingston upon Hull.
The researchers found that, in general, the higher the level of deprivation in an area, the lower the average menu healthiness across its out-of-home food outlets – and all four categories of food outlets tended to be less healthy in more deprived areas.
Not only that, but out-of-home food outlets also tended to cluster in more deprived areas. In the most deprived areas, there were 8.39 food outlets per 1,000-3,000 people, compared to just 3.85 in the least deprived areas.
“There’s a clear pattern between the healthiness of menus at out-of-home food outlets in an area and its level of deprivation. This can create a ‘double burden’ for people living in deprived neighbourhoods, where there are more outlets and these tend to be less healthy, compared to less deprived neighbourhoods."Yuru Huang
“On top of this, there are studies that show, for example, that people with the lowest income were more likely to be obese when living in areas with a high proportion of fast-food outlets. This could even create a ‘triple burden’ for people living in these areas.”
The researchers acknowledge that the menu healthiness score does not capture the intricate nuances of the menu, such as portion size, cooking methods, and levels of food processing. This could be important, as interventions such as healthy catering awards introduced by local government focus on aspects like smaller portion sizes, reducing salt, and switching cooking oils.
This work was supported by the Medical Research Council and Gates Cambridge.
Reference
Huang, Y et al. Assessing the healthiness of menus of all out-of-home food outlets and its socioeconomic patterns in Great Britain. Health & Place; 5 Dec 2023 ; DOI: 10.1016/j.healthplace.2023.103146
Images
- Woman using a food delivery app on her mobile phone (David Espejo/Getty Images)
- Woman serving a customer in a takeaway outlet (SolStock/Getty Image)
- Person eating sushi (Betsai Ekmeiro)
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TopBuilt with Shorthand { setTimeout(() => { document.querySelectorAll('#main a').forEach(link => link.classList.remove('campl-external')); }, 2050); }); //--> Summary:Cambridge researchers have used artificial intelligence to predict the healthiness of café, takeaway and restaurant menus at outlets across Britain and used this information to map which of its local authorities have the most and least healthy food environments.
Image: Affiliation (schools and institutions): School of Clinical MedicineMedical Research Council (MRC) Epidemiology UnitCambridge Public HealthExternal Affiliations: Medical Research CouncilGates Cambridge TrustPeople (our academics and staff): Jean AdamsYuru HuangSection: ResearchSuper Tags: Health and medicineShorthand Story Description/Subtitle: Study highlights ‘double burden’ of unhealthy food environment in deprived areasShorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/244861/UFAfrQs7nX/assets/ha6yCgV8pC/gettyimages-2005442904-land-thumbnail.jpgGenetic mutation in a quarter of all Labradors hard-wires them for obesity
This obesity-driving combination means that dog owners must be particularly strict with feeding and exercising their Labradors to keep them slim.
The mutation is in a gene called POMC, which plays a critical role in hunger and energy use.
Around 25% of Labradors and 66% of flatcoated retriever dogs have the POMC mutation, which researchers previously showed causes increased interest in food and risk of obesity.
The new study reveals how the mutation profoundly changes the way Labradors and flatcoated retrievers behave around food. It found that although they don’t need to eat more to feel full, they are hungrier in between meals.
In addition, dogs with the POMC mutation were found to use around 25% less energy at rest than dogs without it, meaning they don’t need to consume as many calories to maintain a healthy body weight.
“We found that a mutation in the POMC gene seems to make dogs hungrier. Affected dogs tend to overeat because they get hungry between meals more quickly than dogs without the mutation,” said Dr Eleanor Raffan, a researcher in the University of Cambridge’s Department of Physiology, Development and Neuroscience who led the study.
She added: “All owners of Labradors and flatcoated retrievers need to watch what they’re feeding these highly food-motivated dogs, to keep them a healthy weight. But dogs with this genetic mutation face a double whammy: they not only want to eat more, but also need fewer calories because they’re not burning them off as fast.”
The POMC mutation was found to alter a pathway in the dogs’ brains associated with body weight regulation. The mutation triggers a starvation signal that tells their body to increase food intake and conserve energy, despite this being unnecessary.
The results are published today in the journal Science Advances.
Raffan said: “People are often rude about the owners of fat dogs, blaming them for not properly managing their dogs’ diet and exercise. But we’ve shown that Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.”
The researchers say owners can keep their retrievers distracted from this constant hunger by spreading out each daily food ration, for example by using puzzle feeders or scattering the food around the garden so it takes longer to eat.
In the study, 87 adult pet Labrador dogs - all a healthy weight or moderately overweight - took part in several tests including the ‘sausage in a box’ test.
First, the dogs were given a can of dogfood every 20 minutes until they chose not to eat any more. All ate huge amounts of food, but the dogs with the POMC mutation didn’t eat more than those without it. This showed that they all feel full with a similar amount of food.
Next, on a different day, the dogs were fed a standard amount of breakfast. Exactly three hours later they were offered a sausage in a box and their behaviour was recorded. The box was made of clear plastic with a perforated lid, so the dogs could see and smell the sausage, but couldn’t eat it.
The researchers found that dogs with the POMC mutation tried significantly harder to get the sausage from the box than dogs without it, indicating greater hunger.
The dogs were then allowed to sleep in a special chamber that measured the gases they breathed out. This revealed that dogs with the POMC mutation burn around 25% fewer calories than dogs without it.
The POMC gene and the brain pathway it affects are similar in dogs and humans. The new findings are consistent with reports of extreme hunger in humans with POMC mutations, who tend to become obese at an early age and develop a host of clinical problems as a result.
Drugs currently in development for human obesity, underactive sexual desire and certain skin conditions target this brain pathway, so understanding it fully is important.
A mutation in the POMC gene in dogs prevents production of two chemical messengers in the dog brain, beta-melanocyte stimulating hormone (β-MSH) and beta-endorphin, but does not affect production of a third, alpha-melanocyte stimulating hormone (α-MSH).
Further laboratory studies by the team suggest that β-MSH and beta-endorphin are important in determining hunger and moderating energy use, and their role is independent of the presence of α-MSH. This challenges the previous belief, based on research in rats, that early onset human obesity due to POMC mutations is caused only by a lack of α-MSH. Rats don’t produce beta-melanocyte stimulating hormone, but humans and dogs produce both α- and β-MSH.
The research was funded by The Dogs Trust and Wellcome.
Reference: Dittmann, M.T. et al: ‘Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model.’ Science Advances, March 2024. DOI: 10.1126/sciadv.adj3823
New research finds around a quarter of Labrador retriever dogs face a double-whammy of feeling hungry all the time and burning fewer calories due to a genetic mutation.
Obesityanimal behaviouranimal healthEleanor RaffanDepartment of Physiology, Development and Neuroscience (PDN)MRC Metabolic Diseases UnitMetabolic Research LaboratoriesWellcome-MRC Institute of Metabolic ScienceNIHR Cambridge Biomedical Research CentreSchool of the Biological SciencesSchool of the Physical SciencesLabradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.Eleanor RaffanJane GoodallLabrador retriever dog
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.
Low iron levels resulting from infection could be key trigger of long COVID
The discovery not only points to possible ways to prevent or treat the condition, but could help explain why symptoms similar to those of long COVID are also commonly seen in a number of post-viral conditions and chronic inflammation.
Although estimates are highly variable, as many as three in 10 people infected with SARS-CoV-2 could go on to develop long COVID, with symptoms including fatigue, shortness of breath, muscle aches and problems with memory and concentration (‘brain fog’). An estimated 1.9 million people in the UK alone were experiencing self-reported long COVID as of March 2023, according to the Office of National Statistics.
Shortly after the start of the COVID-19 pandemic, researchers at the University of Cambridge began recruiting people who had tested positive for the virus to the COVID-19 cohort of the National Institute for Health and Care Research (NIHR) BioResource. These included asymptomatic healthcare staff identified via routine screening through to patients admitted to Cambridge University Hospitals NHS Foundation Trust, some to its intensive care unit.
Over the course of a year, participants provided blood samples, allowing researchers to monitor changes in the blood post-infection. As it became clear that a significant number of patients would go on to have symptoms that persisted – long COVID – researchers were able to track back through these samples to see whether any changes in the blood correlated with their later condition.
In findings published in Nature Immunology, researchers at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, together with colleagues at Oxford, analysed blood samples from 214 individuals. Approximately 45% of those questioned about their recovery reported symptoms of long COVID between three and ten months later.
Professor Ken Smith, who was Director of CITIID at the time of the study and will take up a position as Director of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia, in April, said: “Having recruited a group of people with SARS-CoV-2 early in the pandemic, analysis of several blood samples and clinical information collected over a 12 month period after infection has proved invaluable in giving us important and unexpected insights into why, for some unlucky individuals, initial SARS-CoV-2 infection is followed by months of persistent symptoms.”
The team discovered that ongoing inflammation – a natural part of the immune response to infection – and low iron levels in blood, contributing to anaemia and disrupting healthy red blood cell production, could be seen as early as two weeks post COVID-19 in those individuals reporting long COVID many months later.
Early iron dysregulation was detectable in the long COVID group independent of age, sex, or initial COVID-19 severity, suggesting a possible impact on recovery even in those who were at low risk for severe COVID-19, or who did not require hospitalisation or oxygen therapy when sick.
Dr Aimee Hanson, who worked on the study while at the University of Cambridge, and is now at the University of Bristol, said: “Iron levels, and the way the body regulates iron, were disrupted early on during SARS-CoV-2 infection, and took a very long time to recover, particularly in those people who went on to report long COVID months later.
“Although we saw evidence that the body was trying to rectify low iron availability and the resulting anaemia by producing more red blood cells, it was not doing a particularly good job of it in the face of ongoing inflammation.”
Interestingly, although iron dysregulation was more profound during and following severe COVID-19, those who went on to develop long COVID after a milder course of acute COVID-19 showed similar patterns in the blood. The most pronounced association with long COVID was how quickly inflammation, iron levels and regulation returned to normal following SARS-CoV-2 infection – though symptoms tended to continue long after iron levels had recovered.
Co-author Professor Hal Drakesmith, from the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, said iron dysregulation is a common consequence of inflammation and is a natural response to infection.
“When the body has an infection, it responds by removing iron from the bloodstream. This protects us from potentially lethal bacteria that capture the iron in the bloodstream and grow rapidly. It’s an evolutionary response that redistributes iron in the body, and the blood plasma becomes an iron desert.
“However, if this goes on for a long time, there is less iron for red blood cells, so oxygen is transported less efficiently affecting metabolism and energy production, and for white blood cells, which need iron to work properly. The protective mechanism ends up becoming a problem.”
The findings may help explain why symptoms such as fatigue and exercise intolerance are common in long COVID, as well as in several other post-viral syndromes with lasting symptoms.
The researchers say the study points to potential ways of preventing or reducing the impact of long COVID by rectifying iron dysregulation in early COVID-19 to prevent adverse long-term health outcomes.
One approach might be controlling the extreme inflammation as early as possible, before it impacts on iron regulation. Another approach might involve iron supplementation; however as Dr Hanson pointed out, this may not be straightforward.
“It isn't necessarily the case that individuals don't have enough iron in their body, it's just that it’s trapped in the wrong place,” she said. “What we need is a way to remobilise the iron and pull it back into the bloodstream, where it becomes more useful to the red blood cells.”
The research also supports ‘accidental’ findings from other studies, including the IRONMAN study, which was looking at whether iron supplements benefited patients with heart failure – the study was disrupted due to the COVID-19 pandemic, but preliminary findings suggest that trial participants were less likely to develop severe adverse effects from COVID-19. Similar effects have been observed among people living with the blood disorder beta-thalassemia, which can cause individuals to produce too much iron in their blood.
The research was funded by Wellcome, the Medical Research Council, NIHR and European Union Horizon 2020 Programme.
Reference
Hanson, AL et al. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19. Nat Imm; 1 March 2024; DOI: 10.1038/s41590-024-01754-8
Problems with iron levels in the blood and the body’s ability to regulate this important nutrient as a result of SARS-CoV-2 infection could be a key trigger for long COVID, new research has discovered.
COVID-19Ken SmithAimee HansonNIHR BioresourceUniversity of OxfordSchool of Clinical MedicineCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)Department of MedicineCambridge University Hospitals NHS Foundation TrustIron levels, and the way the body regulates iron, were disrupted early on during SARS-CoV-2 infection, and took a very long time to recover, particularly in those people who went on to report long COVID months laterAimee HansonMalachi CowieA man sitting on a couch holding his head in his hands
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NHS trial of sponge-on-a-string test replaces need for endoscopy for thousands of patients
The NHS pilot, which has tested over 8,500 patients with the ‘capsule sponge test’, showed almost eight out of 10 patients who completed a test were discharged without the need for further testing, freeing up endoscopy capacity for higher risk patients and those referred for urgent tests for oesophageal cancer.
The test involves patients swallowing a small capsule-shaped device that contains a tiny sponge that collects cell samples for analysis before being extracted via a string thread attached to the sponge. It has been developed by Professor Rebecca Fitzgerald, Director of the Early Cancer Institute at the University of Cambridge.
Professor Fitzgerald said: “It is very exciting to see the positive results of the NHS England real-world pilot for our capsule-sponge test. This is a major step forward to making this simple test more routinely available outside of clinical trials. Timely diagnosis is vital for improving outcomes for patients.”
Barrett’s oesophagus – a condition affecting the food pipe which can go on to cause oesophageal cancer in some patients – is usually diagnosed or ruled out via endoscopy (a camera test of the food pipe) following a GP referral to a gastroenterologist or other specialist practitioner who can carry out the procedure.
The sponge-on-a-string test being trialled by the NHS can instead be carried out quickly in a short appointment, without the need for sedation.
Amanda Pritchard, NHS chief executive, said: “Thousands of people have now benefitted from this incredibly efficient test on the NHS – while the sponge on a string is small in size, it can make a big difference for patients – they can conveniently fit the test into their day and it can often replace the need for an endoscopy while also helping to reduce waiting lists by freeing up staff and resources.
“The NHS is always striving to adopt the latest innovations and new ways of working that help improve patient experience and increase efficiency simple sponge on a string test is just one example of many pioneering tools we’ve trialled in recent years to help diagnose and treat people sooner.”
In a survey of over 250 patients who had the capsule sponge test, patients often said they would recommend the test to a friend or family member, and 94% of patients reported experiencing only mild or no pain at all.
The NHS began piloting the test during the pandemic when there was increased pressure on services and a growing backlog for endoscopy.
Gastro-oesophageal reflux, also known as acid reflux, is a relatively common condition, affecting around one to two in every ten people to some degree, and some of these people may already have or will develop Barrett’s oesophagus, which is a precursor to oesophageal cancer.
There are around 9,300 new oesophageal cancer cases in the UK every year. The key to saving lives is to detect it an earlier stage of Barrett's oesophagus before it becomes cancerous.
The NHS pilot was launched at 30 hospital sites across 17 areas in England including Manchester, Plymouth, London, Kent and Cumbria. Evaluation of the pilot showed that using capsule sponge was highly cost effective compared to using endoscopy-only for diagnosing patients – saving around £400 per patient.
Patients with positive results from the capsule sponge test who were referred on for an endoscopy had the highest prevalence of Barrett’s oesophagus at 27.2%, compared to zero patients with negative results who completed an endoscopy.
One of the first pilot sites at East and North Hertfordshire NHS Trust has now performed around 1,400 capsule sponge tests – offering to both patients with reflux symptoms via a new consultant led, nurse run early diagnosis service, as well as to patients on an existing Barrett’s surveillance programme.
In the first 1000 patients, the capsule test identified Barrett’s in 6% patients with reflux and found two new cancers and three patients with dysplasia who may have had a longer time to diagnosis otherwise. While 72% reflux patients were discharged back to their GP without the need for an endoscopy.
As of January, 368 patients have had a positive test result of whom about half have confirmed Barrett's oesophagus.
Dr Danielle Morris, a consultant gastroenterologist at East and North Hertfordshire NHS Trust, said: “Using the capsule sponge test as a diagnosis triage tool has had huge benefits for patients, avoiding the need for unnecessary gastroscopy in almost seven out of 10 patients, and helping to reduce endoscopy waiting lists enabling us to prioritise those who really need endoscopy to have it done quickly.
“The test is performed by a single trained practitioner in an outpatient setting, so it is very resource light compared to gastroscopy, and our patients are very supportive of the service – with almost nine in 10 patients preferring the capsule sponge to a gastroscopy.”
Adapted from a press release from NHS England.
A new test to help diagnose a condition that can lead to oesophageal cancer – developed by Cambridge researchers and trialled by the NHS – has reduced the need for invasive endoscopy in thousands of low-risk patients.
Canceroesophageal cancerRebecca FitzgeraldSchool of Clinical MedicineEarly Cancer InstituteCambridge Cancer CentreIt is very exciting to see the positive results of the NHS England real-world pilot for our capsule-sponge testRebecca FitzgeraldCytedCapsule and sponge
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Treating newly-diagnosed Crohn's patients with advanced therapy leads to dramatic improvements in outcomes
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Improving outcomes for Crohn's patients
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Improving outcomes for Crohn's patients
Treating newly-diagnosed patients with advanced therapy leads to dramatic improvements in outcomes
22 February 2024
A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold.The PROFILE trial, led by researchers at the University of Cambridge, involved 386 patients with newly-diagnosed active Crohn’s disease. It sought to test whether a biomarker – a genetic signature – could predict which patients were at greatest risk of relapses of their condition, and to test two different approaches to treating the disease.
Crohn’s disease is a life-long condition characterised by inflammation of the digestive tract. It affects around one in 350 people in the UK. Even at its mildest, it can cause symptoms that have a major impact on quality of life including: stomach pain, diarrhoea, weight loss and fatigue. Typically patients experience ‘flares’ of inflammation, where their condition worsens for a time, producing more symptoms and progressive bowel damage. As many as one in 10 patients will require urgent abdominal surgery to treat their condition within their first year of diagnosis.
Medical illustration of Crohn's Disease (BruceBlaus)
Medical illustration of Crohn's Disease (BruceBlaus)
The PROFILE trial was sponsored by Cambridge University Hospitals (CUH) NHS Foundation Trust and the University of Cambridge. It recruited from 40 hospitals across the UK and was supported by the National Institute for Health and Care Research (NIHR) Clinical Research Network. The results are published today in The Lancet Gastroenterology and Hepatology.
While the biomarker did not prove useful in selecting treatments for individual patients, a ‘top-down’ treatment strategy involving use of the drug infliximab straight after diagnosis, showed dramatic results.
Infliximab works by blocking a protein found in the body’s immune system, TNF (tumour necrosis factor)-alpha, which plays an important role in inflammation. The drug is administered through regular intravenous infusions directly into the bloodstream or injections under the skin. However, due to historical concerns about cost and side-effects – including an increased risk of infection related to immunosuppression – it is currently only offered when patients experience regular flare-ups that do not respond to less potent treatments.
In the PROFILE trial, patients were assigned at random to one of two treatment groups. Each group was given a different treatment strategy and patients were followed up over the course of a year.
The first group was treated using an ‘accelerated step-up’ approach, which is the conventional treatment strategy used in the UK and across most countries around the world. In this group, patients only started on infliximab if their disease was progressing and not responding to other simpler treatments.
The second group, however, was treated using ‘top-down’ therapy – that is, they were provided with infliximab as soon as possible after their diagnosis, regardless of the severity of their symptoms.
The results were dramatic: 80% of people receiving the top-down therapy had both symptoms and inflammatory markers controlled throughout the course of the entire year compared to only 15% of people receiving the accelerated step-up therapy.
Two-thirds (67%) of patients in the ‘top-down’ group had no ulcers seen on their endoscopy camera test at the end of the trial – something known as endoscopic remission. Endoscopic remission is considered very important as this has been consistently associated with decreased risk of later complications in Crohn’s disease. Most previous clinical trials of therapies have been considered highly successful based on getting 20 to 30% of patients into endoscopic remission.
As well as these findings, patients in the top-down arm also had higher quality of life scores, less use of steroid medication and lower number of hospitalisations.
Strikingly, while around one in 20 patients (5%) in the conventional treatment arm of the trial required urgent abdominal surgery for their Crohn's disease, only one in 193 (0.5%) receiving the ‘top-down’ therapy required such surgery.
Dr Nuru Noor from the Department of Medicine at the University of Cambridge, one of the study’s lead researchers and first author of the trial, said: “Historically, treatment with an advanced therapy like infliximab within two years of diagnosis has been considered ‘early’ and an ‘accelerated step-up’ approach therefore ‘good enough’. But our findings redefine what should be considered early treatment.
“As soon as a patient is diagnosed with Crohn’s disease, the clock is ticking – and has likely been ticking for some time – in terms of damage happening to the bowel, so there’s a need to start on an advanced therapy such as infliximab as soon as possible."
Dr Nuru Noor
"We’ve shown that by treating earlier, we can achieve better outcomes for patients than have previously been reported.”
In fact, say the researchers, the improvements seen among the trial patients receiving ‘top-down’ therapy might be even more stark compared to usual clinical care. Few patients with Crohn’s disease in standard clinical care receive the rapid, ‘accelerated step-up’ approach provided by the trial protocol, and so the benefits of implementing a ‘top-down’ approach in standard clinical care might be even more pronounced.
Crucially, the team found no difference in risk of serious infection between treatment strategies, suggesting that infliximab straight after diagnosis was well tolerated, contrary to previous concerns about its safety. In addition, the cost of the drug, which is now an off-patent, generic and ‘biosimilar' medicine, has fallen considerably from around £15,000 to around £3,000 per patient per year.
Chief Investigator of the PROFILE trial Professor Miles Parkes, Director of the NIHR Cambridge Biomedical Research Centre, said: “Up until now, the view has been ‘Why would you use a more expensive treatment strategy and potentially over-treat people if there's a chance they might do fine anyway?’
“As we’ve shown, and as previous studies have demonstrated, there’s actually a pretty high risk that an individual with Crohn’s disease will experience disease flares and complications even in the first year after diagnosis.
“We now know we can prevent the majority of adverse outcomes, including need for urgent surgery, by providing a treatment strategy that is safe and becoming increasingly affordable."
"If you take a holistic view of safety, including the need for hospitalisations and urgent surgery, then the safest thing from a patient point of view is to offer ‘top-down’ therapy straight after diagnosis rather than having to wait and use ‘step-up’ treatment.”
Professor Miles Parkes
The PROFILE team are now actively working on an analysis of the health economics to see whether the benefits of the therapy outweigh its cost.
Professor Parkes added: “It's not just those five per cent of people requiring surgery that we need to think about. In the ‘step-up’ arm lots of people experienced disease flares without necessarily needing surgery. And every time somebody flares, they require several consultations with specialist doctors and nurses, clinical investigations such as scans and colonoscopies, time off work, time out of education and so on – all leading to major impacts on quality of life for individuals.”
While there are other anti-TNF drugs, such as adalimumab, that work in a similar manner to infliximab and are significantly cheaper, more research is required to understand if it would be as clinically effective.
Ruth Wakeman, Director of Services, Advocacy & Evidence at Crohn’s & Colitis UK said: “Crohn’s Disease affects over 200,000 people in the UK and we know that many of them have symptoms for a long time before they are diagnosed. But diagnosis is not the end of their journey, and the trial and error involved in finding the right treatment can be challenging and distressing.
“This study shows what a dramatic difference early treatment with advanced therapy can make to newly-diagnosed patients. People with Crohn’s don’t want to be stuck in hospital or having surgery, they want to be out in the world, living their lives. Anything that speeds up the path to remission can only be a good thing.”
“If the drug had been offered in the first place, things could have been very different.”Toby Moore (Credit: Mark Danson)
Toby Moore (Credit: Mark Danson)
Toby Moore, 28, was just ten years old when it became clear there was something wrong.“I was at primary school at the time and was getting lots of abdominal pain, lots of going to the toilet and vomiting, low energy levels – I was effectively unable to consume any food or drink without some kind of problem. It was just terrible.”
He visited the GP repeatedly over six months, where among other things he was told it was due to the stress of Year Six exams. He says that for his mother and father, it was probably the most challenging time of their lives as parents.
“I was eventually referred to a paediatric gastroenterologist specialist who within 30 seconds of looking at me said, ‘Right. I think you have Crohn's disease. I'd like to do these tests,’ and off we went.”
The specialist was correct. He put Toby on an ‘elemental diet’ to manage his condition, which meant that for six weeks he could eat no food or drinks (other than water), only prescription shakes aimed at allowing his digestive system to heal. Toby then had to reintroduce different foods into his diet to see if they could identify what triggered his condition.
Not long afterwards, he had a ‘flare up’, with his symptoms worsening significantly. His local Peterborough hospital was unable to help and so he was referred to the Royal Free Hospital in London. There, his parents had to make the difficult decision of whether he should receive abdominal surgery or go onto biologic medication. They chose the latter, and Toby was put on infliximab.
“If you asked my parents now, they'd call it a light switch drug. I was infused with it on a Thursday and by the Sunday I was a different person. I was eating, drinking, my symptoms had stopped. It was unbelievable. Arguably, if that had been offered in the first place instead of the lighter approach, things could have been very different.”
Toby was on infliximab for several years, but was taken off the drug in late secondary school when he became unwell – “not in a Crohn's disease way, something else was going on”. He was taken into hospital, where the doctors immediately stopped the treatment, concerned it was a trigger.
Toby was transferred to Addenbrooke’s Hospital, where Dr Miles Parkes took over his treatment. It turned out that Toby also had large vessel vasculitis, another autoimmune condition. Whereas Crohn’s affects your digestive system, this affects blood vessels. It causes the aorta, the main blood vessel in your body, to become narrowed, which causes symptoms including weight loss, unexplained lower back pain and fatigue.
Since then, Toby has been on a number of different biologic treatments, each working for a while before their effects wear off, he experiences another flare up, and is prescribed a different drug. Were it not for the drugs, he says his life would be very different.
“It can be quite debilitating, especially when it's flaring up, as I'm sure you can imagine, when you have minimal control over certain bodily functions. It's not the most pleasant.”
His current medication, upadacitinib, involves taking a daily pill. It has helped him manage his condition – flare ups aside – allowing him to live a relatively normal life, hold down a steady job as a chef in a local hospice , close to where he lives, and start a family. But he still has to be very careful.
“Where possible I try to avoid stressful situations that life throws at you. When you live at your mum and dad's life's a bit more simple, you've got a few less responsibilities, so stress is slightly less, but when you go out into the big wide world – and I've got a two-and-a-half year old daughter now – that obviously adds a new dynamic to your life!”
Toby has nothing but praise for the NHS. “They’ve been just phenomenal. Miles is very good at nipping things in the bud straight away. He always actions things, he doesn't just say, ‘Well, we'll see how you are in a month’. So it never gets too out of control.
"My opinion of the NHS is really, really high. They've been a lifeline for me.”
Toby Moore
The research was funded by Wellcome and PredictImmune Ltd and supported by the NIHR Cambridge Biomedical Research Centre.
Reference
Noor NM, Lee JC, Bond S, et al. PROFILE: a multi-centre, randomised, open-label, biomarker-stratified clinical trial of treatment strategies for patients with newly-diagnosed Crohn’s disease. Lancet Gastroenterol Hepatol; 22 Feb 2024; DOI: 10.1016/S2468-1253(24)00034-7
Main image: Crohn's disease illustration (SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY)
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
A large-scale clinical trial of treatment strategies for Crohn’s disease has shown that offering early advanced therapy to all patients straight after diagnosis can drastically improve outcomes, including by reducing the number of people requiring urgent abdominal surgery for treatment of their disease by ten-fold.
Image: Affiliation (schools and institutions): School of Clinical MedicineDepartment of MedicineNIHR Cambridge Biomedical Research CentreExternal Affiliations: NIHR Cambridge Biomedical Research CentreWellcomePredictImmunePeople (our academics and staff): Nuru NoorMiles ParkesSubject (including Spotlight on ... where applicable): Crohn's diseaseStoriesSection: ResearchSuper Tags: Health and medicineShorthand Story Description/Subtitle: Treating newly-diagnosed patients with advanced therapy leads to dramatic improvements in outcomesShorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/244621/MATQxWmsAi/assets/19k40RASYR/gettyimages-1683230459-land-thumbnail.jpgLong COVID linked to persistently high levels of inflammatory protein: a potential biomarker and target for treatments
A University of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue and highlights an immunological mechanism underlying the disease, which could pave the way for the development of much needed therapies, and provide a head start in the event of a future coronavirus pandemic.
The study, published today in Science Advances, followed a group of patients with Long COVID fatigue for over 2.5 years, to understand why some recovered and others did not.
Long COVID continues to affect millions of people globally and is placing a major burden on health services. An estimated 1.9 million people in the UK alone (2.9% of the population) were experiencing self-reported Long COVID as of March 2023, according to the ONS. Fatigue remains by far the most common and debilitating symptom and patients are still waiting for an effective treatment.
The study shows that initial infection with SARS-CoV-2 triggers production of the antiviral protein IFN-γ, which is a normal reaction from the immune system. For most people, when their infection clears, COVID-19 symptoms cease and production of this protein stops, but the researchers found that high levels of IFN-γ persisted in some Long COVID patients for up to 31 months.
“We have found a potential mechanism underlying Long COVID which could represent a biomarker – that is, a tell-tale signature of the condition. We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis,” said co-author, Dr Benjamin Krishna, from the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID).
The research began in 2020 when Dr Nyarie Sithole set up a Long COVID clinic in Cambridge’s Addenbrooke’s Hospital, where he started collecting blood samples from patients and set about studying their immunology. Sithole soon enlisted the support of Dr Benjamin Krishna and Dr Mark Wills from the University of Cambridge’s Dept. of Medicine.
“When the clinic started, a lot of people didn't even believe Long COVID was real,” Dr Sithole said. “We are indebted to all the patients who volunteered for this study, without whose support and participation we would obviously not have accomplished this study”.
The team studied 111 COVID-confirmed patients admitted to Addenbrooke’s Hospital CUH, Royal Papworth Hospital and Cambridge and Peterborough NHS Foundation Trusts at 28 days, 90 days and 180 days following symptom onset. Between August 2020 and July 2021, they recruited 55 Long COVID patients – all experiencing severe symptoms at least 5 months after acute COVID-19 – attending the Long COVID clinic at Addenbrooke’s.
The researchers analysed blood samples for signs of cytokines, small proteins crucial to the functioning of immune system cells and blood cells. They found that the white blood cells of individuals infected with SARS-CoV-2 produced IFN-γ, a pro inflammatory molecule, and that this persisted in Long COVID patients.
Dr Krishna said: “Interferon gamma can be used to treat viral infections such as hepatitis C but it causes symptoms including fatigue, fever, headache, aching muscles and depression. These symptoms are all too familiar to Long COVID patients. For us, that was another smoking gun.”
By conducting ‘cell depletion assays’, the team managed to identify the precise cell types responsible for producing IFN-γ. They pinpointed immune cells known as CD8+ T cells but found that they required contact with another immune cell type: CD14+ monocytes.
Previous studies have identified IFN-γ signatures using different approaches and cohorts, but this study’s focus on fatigue revealed a much stronger influence. Also, while previous studies have noticed IFN-y levels rising, they have not followed patients long enough to observe when they might drop back down.
The Cambridge team followed its Long COVID cohort for up to 31 months post-infection. During this follow up period, over 60% of patients experienced resolution of some, if not all, of their symptoms which coincided with a drop in IFN-γ.
Vaccination helping Long COVID patients
The team measured IFN-γ release in Long COVID patients before and after vaccination and found a significant decrease in IFN-γ post vaccination in patients whose symptoms resolved.
“If SARS-CoV-2 continues to persist in people with Long COVID, triggering an IFN-γ response, then vaccination may be helping to clear this. But we still need to find effective therapies,” Dr Krishna said.
“The number of people with Long COVID is gradually falling, and vaccination seems to be playing a significant role in that. But new cases are still cropping up, and then there is the big question of what happens when the next coronavirus pandemic comes along. We could face another wave of Long COVID. Understanding what causes Long COVID now could give us a crucial head start.”
Microclotting
Some well-publicised previous studies have proposed microclotting as a principle cause of Long COVID. While not ruling out a role of some kind, these new findings suggest that microclotting cannot be the only or the most significant cause.
Classifying long COVID
This study argues that the presence of IFN-γ could be used to classify Long COVID into subtypes which could be used to personalise treatment.
“It’s unlikely that all the different Long COVID symptoms are caused by the same thing. We need to differentiate between people and tailor treatments. Some patients are slowly recovering and there are those who are stuck in a cycle of fatigue for years on end. We need to know why,” Dr Krishna said.
Reference
B. A. Krishna et al., ‘Spontaneous, persistent, T-cell dependent IFN-γ release in patients who progress to long COVID’, Science Advances (2024). DOI: 10.1126/sciadv.adi9379
SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.
COVID-19Nyarie SitholeBenjamin KrishnaRoyal Papworth Hospital NHS Foundation TrustCambridge and Peterborough NHS Foundation TrustSchool of Clinical MedicineCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)Addenbrooke's HospitalSidney Sussex CollegeWe hope that this could help to pave the way to develop therapies and give some patients a firm diagnosisBenjamin KrishnaAnnie Spratt via Unsplashwoman sat on sofa in the dark placing a hand to her forehead
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Scientists identify genes linked to DNA damage and human disease
The work, published in Nature, provides insights into cancer progression and neurodegenerative diseases as well as a potential therapeutic avenue in the form of a protein inhibitor.
The genome contains all the genes and genetic material within an organism's cells. When the genome is stable, cells can accurately replicate and divide, passing on correct genetic information to the next generation of cells. Despite its significance, little is understood about the genetic factors governing genome stability, protection, repair, and the prevention of DNA damage.
In this new study, researchers from the UK Dementia Research Institute, at the University of Cambridge, and the Wellcome Sanger Institute set out to better understand the biology of cellular health and identify genes key to maintaining genome stability.
Using a set of genetically modified mouse lines, the team identified 145 genes that play key roles in either increasing or decreasing the formation of abnormal micronuclei structures. These structures indicate genomic instability and DNA damage, and are common hallmarks of ageing and diseases.
The most dramatic increases in genomic instability were seen when the researchers knocked out the gene DSCC1, increasing abnormal micronuclei formation five-fold. Mice lacking this gene mirrored characteristics akin to human patients with a number of rare genetic disorders, further emphasising the relevance of this research to human health.
Using CRISPR screening, researchers showed this effect triggered by DSCC1 loss could be partially reversed through inhibiting protein SIRT1. This offers a highly promising avenue for the development of new therapies.
The findings help shed light on genetic factors influencing the health of human genomes over a lifespan and disease development.
Professor Gabriel Balmus, senior author of the study at the UK Dementia Research Institute at the University of Cambridge, formerly at the Wellcome Sanger Institute, said: “Continued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causes, with the goal of improving outcomes and the overall quality of life for individuals across various conditions.”
Dr David Adams, first author of the study at the Wellcome Sanger Institute, said: “Genomic stability is central to the health of cells, influencing a spectrum of diseases from cancer to neurodegeneration, yet this has been a relatively underexplored area of research. This work, of 15 years in the making, exemplifies what can be learned from large-scale, unbiased genetic screening. The 145 identified genes, especially those tied to human disease, offer promising targets for developing new therapies for genome instability-driven diseases like cancer and neurodevelopmental disorders.”
This research was supported by Wellcome and the UK Dementia Research Institute.
Reference
Adams, DJ et al. Genetic determinants of micronucleus formation in vivo. Nature; 14 Feb 2024; DOI: 10.1038/s41586-023-07009-0
Adapted from a press release from the Wellcome Sanger Institute.
Cambridge scientists have identified more than one hundred key genes linked to DNA damage through systematic screening of nearly 1,000 genetically modified mouse lines.
Spotlight on neurosciencedementianeurodegenerationGabriel BalmusWellcome Sanger InstituteWellcomeUK Dementia Research InstituteSchool of Clinical MedicineUK Dementia Research InstituteContinued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causesGabriel BalmusqimonoDNA puzzle
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School uniform policies linked to students getting less exercise, study finds
The University of Cambridge study used data about the physical activity participation of more than a million five-to-17-year-olds internationally. It found that in countries where a majority of schools require students to wear uniforms, fewer young people tend to meet the average of 60 minutes of physical activity per day recommended by the World Health Organisation (WHO).
Regardless of uniform policies, across most countries fewer girls than boys reach those recommended exercise levels. Among primary school students, however, the difference in activity between girls and boys was found to be wider in countries where most schools mandated uniforms. The same result was not found in secondary school-aged students.
The authors suggest that this could be explained by the fact that younger children get more incidental exercise throughout the school day than older students; for example, through running, climbing and various other forms of active play at break and lunchtimes. There is already evidence that girls feel less comfortable in participating in active play if they are wearing certain types of clothing, such as skirts or dresses.
Importantly, the results do not definitively prove that school uniforms limit children’s physical activity and the researchers stress that “causation cannot be inferred”. Previous, smaller studies however provide support for these findings, indicating that uniforms could pose a barrier. For the first time, the research examines large-scale statistical evidence to assess that claim.
The study was led by Dr Mairead Ryan, a researcher at the Faculty of Education and Medical Research Council (MRC) Epidemiology Unit, University of Cambridge.
“Schools often prefer to use uniforms for various reasons,” Dr Ryan said. “We are not trying to suggest a blanket ban on them, but to present new evidence to support decision-making. School communities could consider design, and whether specific characteristics of a uniform might either encourage or restrict any opportunities for physical activity across the day.”
The WHO recommends that young people get an average of 60 minutes of at least moderate-intensity physical activity per day during the week. The study confirms previous observations that most children and adolescents are not meeting this recommendation, especially girls. The difference in the percentage of boys and girls meeting physical activity guidelines across all countries was, on average, 7.6 percentage points.
Existing evidence suggests that uniforms could be a factor. Previous concerns have, for example, been raised about girls’ PE uniforms and school sports kits. A 2021 study in England found that the design of girls’ PE uniforms deterred students from participating in certain activities, while the hockey player Tess Howard proposed redesigning gendered sports uniforms for similar reasons, after analysing interview and survey data.
Children often get their exercise away from PE and sports lessons, however.
“Activities like walking or cycling to school, breaktime games, and after-school outdoor play can all help young people incorporate physical activity into their daily routines,” Ryan said. “That’s why we are interested in the extent to which various elements of young people’s environments, including what they wear, encourage such behaviours.”
The study analysed existing data on the physical activity levels of nearly 1.1 million young people aged five to 17 in 135 countries and combined this with newly collected data on how common the use of school uniforms is in these countries.
In over 75% of the countries surveyed, a majority of schools required their students to wear uniforms. The study found that in these countries, physical activity participation was lower. The median proportion of all students meeting the WHO recommendations in countries where uniform-wearing was the norm was 16%; this rose to 19.5% in countries where uniforms were less common.
There was a consistent gender gap between boys’ and girls’ physical activity levels, with boys 1.5 times more likely to meet WHO recommendations across all ages. However, the gap widened from 5.5 percentage points at primary school level in non-uniform countries to a 9.8 percentage point difference in countries where uniforms were required in most schools.
The finding appears to match evidence from other studies suggesting that girls are more self-conscious about engaging in physical activity when wearing uniforms in which they do not feel comfortable.
“Girls might feel less confident about doing things like cartwheels and tumbles in the playground, or riding a bike on a windy day, if they are wearing a skirt or dress,” said senior author Dr Esther van Sluijs, MRC Investigator. “Social norms and expectations tend to influence what they feel they can do in these clothes. Unfortunately, when it comes to promoting physical health, that’s a problem.”
The authors of the study argue that there is now enough evidence to warrant further investigation into whether there is a causal relationship between school uniforms and lower activity levels. They also highlight the importance of regular physical activity for all young people, regardless of their gender.
“Regular physical activity helps support multiple physical, mental, and well-being needs, as well as academic outcomes,” Dr Ryan said. “We now need more information to build on these findings, considering factors like how long students wear their uniforms for after school, whether this varies depending on their background, and how broader gendered clothing norms may impact their activity.”
The findings are reported in the Journal of Sport and Health Science.
School uniform policies could be restricting young people from being active, particularly primary school-aged girls, new research suggests.
ChildrenPublic healthMairead RyanEsther van SluijsMedical Research CouncilSchool of the Humanities and Social SciencesSchool of Clinical MedicineFaculty of EducationMedical Research Council (MRC) Epidemiology UnitSocial norms and expectations tend to influence what they feel they can do in these clothes. Unfortunately, when it comes to promoting physical health, that’s a problemEsther van SluijsThirdmanSchool children watching a sports game from indoors
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£3 million UKRI funding to support research into better health, ageing, and wellbeing
UKRI funding of £3 million is awarded today to support a new research cluster, as part of the MRC National Mouse Genetics Network (MRC NMGN), focused on improving existing models of ageing with the aim of improving lifelong health and wellbeing. The cluster is led by scientists at the Universities of Cambridge and Newcastle.
The MRC NMGN focuses on age-related biological changes in model organisms, particularly the mouse, to try and improve our understanding and diagnosis of the most challenging disease area of our time - and generate therapeutic avenues.
This award brings the UKRI’s total investment in the MRC NMGN to £25 million.
The need to improve how people age has become a major requirement of modern societies. Regular increases in life expectancy result in older populations, making healthy ageing essential for a better quality of life and a reduced burden on health and social services.
Understanding the biological mechanisms underlying the ageing process is paramount for tackling the challenges brought about by our older populations.
The new tools generated as a result of this research will be made available to the scientific community to improve understanding of the ageing process, and to provide a resource for preclinical testing and intervention.
Professor Walid Khaled from Cambridge’s Wellcome-MRC Cambridge Stem Cell Institute and Department of Pharmacology, and Co-lead of the new MRC National Mouse Genetics Network Ageing Cluster, said: “I am very pleased to be co-leading this project from Cambridge and I am looking forward to working with the rest of the team from around the UK. ‘Prevention is better than cure’ and so our project will generate a reference map that we will use in the future to assess interventions that could prevent ageing related health decline.”
Professor Anne Ferguson-Smith, Pro-Vice-Chancellor (Research & International Partnerships) and Arthur Balfour Professor of Genetics at Cambridge, said: "Collaboration is central to our research activities in Cambridge. The new Ageing Cluster is a fine example of multiple institutions working together to add value and bring exciting new insight and expertise to advance the critically important field of healthy ageing. I am proud to be part of this important initiative which can deliver new routes to improved health span."
Professor David Burn, Pro Vice Chancellor, Faculty of Medical Sciences at Newcastle University, added: "I am delighted that Newcastle University is an important part of the UKRI Mouse Genetics Network Ageing Cluster. This cluster offers researchers the opportunity to develop new animal models so that we may better understand ageing. This, in turn, will allow us to translate this research into extending healthy lifespan in humans in the future.”
The University is bringing together its world leading expertise to tackle the topic of extending the healthy lifespan. Scientists in the School of Biological Sciences are addressing some of the biggest questions in human biology, including: What if we could identify those at risk of developing chronic age-related conditions before they present in the clinic? What if we could intervene before any symptoms arise and prevent disease onset?
UKRI’s strategy for 2022-2027 aims to harness the full power of the UK’s research and innovation system to tackle major national and global challenges. A total of £75m has been allocated to the theme of Securing better health, ageing and wellbeing, which aims to improve population health, tackle the health inequalities affecting people and communities, and advance interventions that keep us healthier for longer.
Read more about Cambridge research into extending the healthy lifespan.
The University of Cambridge has received UKRI funding for research on age-related biological changes in model organisms as part of a national collaboration.
ageinganimal researchWalid KhaledAnne Ferguson-SmithMedical Research CouncilSchool of the Biological SciencesDepartment of PharmacologyWellcome-MRC Cambridge Stem Cell InstituteMagdalene College‘Prevention is better than cure’ and so our project will generate a reference map that we will use in the future to assess interventions that could prevent ageing related health declineWalid KhaledUnderstanding Animal ResearchBrown GM mouse on hand
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Strongest evidence to date of brain’s ability to compensate for age-related cognitive decline
As we age, our brain gradually atrophies, losing nerve cells and connections and this can lead to a decline in brain function. It’s not fully understood why some people appear to maintain better brain function than others, and how we can protect ourselves from cognitive decline.
A widely accepted notion is that some people’s brains are able to compensate for the deterioration in brain tissue by recruiting other areas of the brain to help perform tasks. While brain imaging studies have shown that the brain does recruit other areas, until now it has not been clear whether this makes any difference to performance on a task, or whether it provides any additional information about how to perform that task.
In a study published in the journal eLife, a team led by scientists at the University of Cambridge in collaboration with the University of Sussex have shown that when the brain recruits other areas, it improves performance specifically in the brains of older people.
Study lead Dr Kamen Tsvetanov, an Alzheimer's Society Dementia Research Leader Fellow in the Department of Clinical Neurosciences, University of Cambridge, said: “Our ability to solve abstract problems is a sign of so-called ‘fluid intelligence’, but as we get older, this ability begins to show significant decline. Some people manage to maintain this ability better than others. We wanted to ask why that was the case – are they able to recruit other areas of the brain to overcome changes in the brain that would otherwise be detrimental?”
Brain imaging studies have shown that fluid intelligence tasks engage the ‘multiple demand network’ (MDN), a brain network involving regions both at the front and rear of the brain, but its activity decreases with age. To see whether the brain compensated for this decrease in activity, the Cambridge team looked at imaging data from 223 adults between 19 and 87 years of age who had been recruited by the Cambridge Centre for Ageing & Neuroscience (Cam-CAN).
The volunteers were asked to identify the odd-one-out in a series of puzzles of varying difficulty while lying in a functional magnetic resonance imaging (fMRI) scanner, so that the researchers could look at patterns of brain activity by measuring changes in blood flow.
As anticipated, in general the ability to solve the problems decreased with age. The MDN was particularly active, as were regions of the brain involved in processing visual information.
When the team analysed the images further using machine-learning, they found two areas of the brain that showed greater activity in the brains of older people, and also correlated with better performance on the task. These areas were the cuneus, at the rear of the brain, and a region in the frontal cortex. But of the two, only activity in the cuneus region was related to performance of the task more strongly in the older than younger volunteers, and contained extra information about the task beyond the MDN.
Although it is not clear exactly why the cuneus should be recruited for this task, the researchers point out that this brain region is usually good at helping us stay focused on what we see. Older adults often have a harder time briefly remembering information that they have just seen, like the complex puzzle pieces used in the task. The increased activity in the cuneus might reflect a change in how often older adults look at these pieces, as a strategy to make up for their poorer visual memory.
Dr Ethan Knights from the Medical Research Council Cognition and Brain Sciences Unit at Cambridge said: “Now that we’ve seen this compensation happening, we can start to ask questions about why it happens for some older people, but not others, and in some tasks, but not others. Is there something special about these people – their education or lifestyle, for example – and if so, is there a way we can intervene to help others see similar benefits?”
Dr Alexa Morcom from the University of Sussex’s School of Psychology and Sussex Neuroscience research centre said: “This new finding also hints that compensation in later life does not rely on the multiple demand network as previously assumed, but recruits areas whose function is preserved in ageing.”
The research was supported by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the European Union’s Horizon 2020 research and innovation programme, the Guarantors of Brain, and the Alzheimer’s Society.
Reference
Knights, E. et al. Neural Evidence of Functional Compensation for Fluid Intelligence Decline in Healthy Ageing. eLife; 6 Feb 2024; DOI: 10.7554/eLife.93327
Scientists have found the strongest evidence yet that our brains can compensate for age-related deterioration by recruiting other areas to help with brain function and maintain cognitive performance.
Spotlight on neuroscienceageingNeuroscienceKamen TsvetanovEthan KnightsMedical Research CouncilEuropean Union Horizon 2020Biotechnology and Biological Sciences Research Council (BBSRC)Guarantors of BrainAlzheimer's SocietyUniversity of SussexSchool of Clinical MedicineDepartment of Clinical NeurosciencesMRC Cognition and Brain Sciences UnitNow that we’ve seen this compensation happening, we can start to ask questions about why it happens for some older people, but not others - is there something special about these people?Ethan KnightsCDCWoman in purple and white floral shirt washing a carrot
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Using AI to tackle society's biggest challenges
Shorthand Story: d7rB3zLKWcShorthand Story Head:
Using AI to tackle society's biggest challenges
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Using AI to tackle society's biggest challenges
5 February 2024
The winners of a new prize supporting ambitious ideas for how artificial intelligence can address critical societal issues are announced today, with projects spanning fertility, climate change, language and communication challenges, mental health, and how local councils deploy AI.The five winners of the challenge - called AI-deas - have been selected by ai@cam: the University of Cambridge’s new flagship mission to drive AI innovation that benefits science, citizens and society. They will receive seed funding to get off the ground and support to scale their impact.
Each project exemplifies the public value ai@cam champions in artificial intelligence research, by being interdisciplinary by design, grounded in real world need, and having a clear plan for cross-sectoral collaboration with external stakeholders – such as affected communities, public sector, industry and NGOs.
After a competitive selection process, which kicked off last year with more than 70 concept papers submitted from across the University's departments, the winning projects will aim to:
- improve understanding, diagnosis and treatment of brain diseases and mental health disorders
- develop cheaper, less invasive and more accessible AI-driven healthcare diagnostics that can be used throughout the conception to childhood journey
- build tools to assess common language and communication challenges and provide tools and technologies to support people with language and communication related disabilities
- develop resources for local authorities to make ethical and informed decisions about the use of AI in their digitalisation initiatives
- equip decision makers find more targeted and effective solutions to the twin climate and biodiversity crises, by using AI to provide better evidence and information.
Professor Anne Ferguson-Smith, Pro-Vice-Chancellor for Research and Steering Group member of ai@cam, said: “These are exactly the kinds of ambitious projects that are vital to delivering AI that serves society, but too often are neglected in the traditional funding landscape, because they require intensive collaboration across disciplines. I’m thrilled we have a mechanism for enabling them. Cambridge is already home to some of the most groundbreaking AI research, and AI-deas encourages further creativity and innovative thinking in this area.“
AI-deas is ai@cam’s first major initiative, and will form part of a wider programme designed to deliver on the University’s AI mission. Through research funding, partnerships within and outside of the university, and education, ai@cam will more powerfully connect what happens in the university lab to the outside world.
Neil Lawrence, DeepMind Professor of Machine Learning and Chair of ai@cam, said: “The positive response we’ve had to the AI-deas initiative proves there’s a vibrant community of researchers across all career levels who are passionate about connecting AI to public interest. AI has the potential to drive progress on the things that actually matter to people. The selected projects in this round of funding show how we can make that happen - for instance, bringing experts in machine learning, fertility and infant neurodevelopment together in a shared mission.”
Diane Coyle, Bennett Professor of Public Policy and Steering Group member of ai@cam, said: “AI innovation is often perceived as being driven by business. While a wealth of exciting work is coming from leading AI companies, they are not going to solve society’s biggest challenges themselves. Interdisciplinary AI research is vital to bridge from technological advances to public value. AI-deas aims to build some of those bridges.”
Responsible AI for better lifelong brain and mental healthBrain diseases and mental health disorders are taking a toll on people throughout their lives. Dementia is the leading cause of death in England and Wales, and different mental health disorders lead to significant reductions in life expectancy.
This project will use the latest advances in AI to better understand brain health and disease. It will explore the environmental, social and neurological factors at play, to develop responsible AI-driven tools that help clinicians predict, diagnose and treat brain diseases and mental health disorders.
The project will be led by the Department of Psychology and delivered by an interdisciplinary team of experts in areas including data science, software engineering, neuroscience and clinical practice from across the university.
Professor Zoe Kourtzi, AI-deas challenge lead, said: "AI-deas is a springboard for thinking outside the box about using AI to tackle real-world challenges like those associated with brain and mental health disorders. Brain and mental health disorders touch every family. Building robust and responsible AI tools has the potential to help clinicians diagnose early, improve patient wellbeing and outcomes and reduce misdiagnosis, making resources available to people that need them the most."
From conception to childhood: Revolutionising women’s health, female fertility and early infant neurodevelopment using AIThe UK has the largest gender health gap in the G20 and declining fertility rates, with women's health issues not well understood.
This project aims to develop cheaper, less invasive and more accurate AI-assisted tests that can be used throughout the conception to childhood journey. These tests will be used to enhance and personalise fertility outcomes. This research will play a key part in improving fertility and women's health outcomes and shed light on the still largely unknown cellular, molecular and genetic mechanisms governing the development of life.
The Departments of Psychology, Computer Science, and Physics among others will lead this project, in partnership with two leading specialty hospitals.
Dr Staci Weiss, AI-deas challenge co-lead said: “AI-deas provides an interdisciplinary platform bringing together data and new AI analytic approaches to accelerate identification of reproductive health biomarkers from embryo through to neonate."
Mo Vali, AI-deas challenge co-lead said: "We will seek to revolutionise reproductive health technology using state-of-the-art AI methods, leveraging Cambridge's long tradition of research in this field. Translating our research from lab to clinic by developing rigorous tests to improve clinical outcomes will benefit the wider public and help to ease the NHS burden.”
Improving language equity and inclusion through AIUsing language to communicate is something many take for granted. However, a significant proportion of the UK population find spoken or written communication more difficult due to sensory, neural or linguistic challenges such as hearing loss, brain injury or language barriers, and can face substantial disadvantages in many aspects of their lives.
This project aims to develop new AI methods to understand and address these challenges to improve equity and inclusion. It will develop new ways to support people with language and communication difficulties. For example, with AI we can assess and diagnose common language and communication conditions at scale, and develop technologies such as intelligent hearing aids, real-time machine translation, or other language aids to support affected individuals at home, work or school.
The MRC Cognition and Brain Sciences Unit will lead this project.
Matt Davis, AI-deas challenge lead, said: "New AI technologies are changing our day-to-day lives: we speak rather than type text messages on our phones, and have conversations with Alexa or Siri. As these systems become more common they may reinforce the barriers faced by those who find communicating through language more difficult.
"Cambridge University hosts the UK’s largest community of researchers working on speech and language technology and have a remarkable breadth and depth of expertise in understanding the real-world impact of language challenges in education, health or work. This project brings these research communities together to develop new AI technologies to support people who find communicating using language a daily challenge in order to improve equity and inclusion."
Decision-making with AI in connected places and cities: Developing an ethical and responsible innovation rooted approach for public value creationPublic sector use of AI is growing, with some local authorities in England already using large language models and predictive analytics to make city-scale decisions. It is important that the use of AI to make decisions is ethical and leads to the desired outcomes.
This project aims to investigate how local authorities in England are using AI to make decisions about issues such as placemaking, land use and mobility, and sustainable water supply systems to create public value. The project will develop resources for local authorities to make ethical and informed choices and the use of AI as part of digitalisation initiatives.
The Department of Engineering will lead this project and facilitate collaboration with local authorities, and among experts in other domains including urban governance, philosophy and ethics.
Dr Kwadwo Oti-Sarpong, AI-deas challenge lead, said: "We're excited to be one of the winners of AI-deas and work on this project with practitioners across disciplines to shape the future of public sector decision-making using AI in creating connected places.
"Understanding how to practically root AI use in ethical considerations, and showing how that can be done, will significantly change how we create the future we want."
AI for climate and natureThe twin climate and biodiversity crises are two of the world’s most complex challenges to tackle. This project aims to develop AI approaches for bringing together a wide range of datasets and accelerating the collation of information.
This work will provide up to date, relevant and robust information for researchers and decision-makers working on climate and biodiversity conservation – opening up the possibility for more targeted and effective solutions to some of our world’s most pressing climate and biodiversity challenges.
Anil Madhavapeddy, AI-deas challenge co-lead, said: “Mitigating the impacts of climate change while maintaining and restoring biodiversity demands urgent, evidence-based action. We're excited to bring together an interdisciplinary team across computer science, ecology, climate and conservation to use AI to empower decision-makers to equitably tackle the biggest challenge of our generation.”
This project is a collaboration between Cambridge Zero, Cambridge Conservation Initiative, Conservation Evidence, Institute for Computing for Climate Science, Conservation Research Institute, Centre for Landscape Regeneration, Cambridge Centre for Carbon Credits and Cambridge Centre for Earth Observation.
To find out more about ai@cam, visit their website.
All images are from Getty Images:
- Butterfly abstract technology background - Shutter2U
- Brain of neuro technology - Yuichiro Chino
- Digital Artificial X-Chromosomes - Usis
- Conversational AI Concept - ArtemisDiana
- Smart city, conceptual illustration - RICHARD JONES/SCIENCE PHOTO LIBRARY
- Tree growth as a leadership concept in digital futuristic polygonal style - Yevhen LahunovT
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
TopBuilt with Shorthand { setTimeout(() => { document.querySelectorAll('#main a').forEach(link => link.classList.remove('campl-external')); }, 2050); }); //--> Summary:The winners of a new prize supporting ambitious ideas for how artificial intelligence can address critical societal issues are announced today, with projects spanning fertility, climate change, language and communication challenges, mental health, and how local councils deploy AI.
Image: Affiliation (schools and institutions): AI@CamSchool of the Biological SciencesSchool of TechnologySchool of Clinical MedicineDepartment of PsychologyDepartment of Computer Science and TechnologyDepartment of EngineeringMRC Cognition and Brain Sciences UnitCambridge ZeroCambridge Conservation InitiativeInstitute for Computing for Climate ScienceChurchill CollegePeople (our academics and staff): Neil LawrenceDiane CoyleAnne Ferguson-SmithZoe KourtziStaci WeissMo ValiMatt DavisKwadwo Oti-SarpongAnil MadhavapeddySubject (including Spotlight on ... where applicable): Artificial intelligenceStoriesSection: ResearchSuper Tags: Health and medicineEnvironmentScienceTechnologySocietyShorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/244291/d7rB3zLKWc/assets/8GN05XDwzm/gettyimages-1155866750-land-cinematic-blue-0.5-thumbnail.jpgCancer isn’t fair – but care should be
Shorthand Story: nT3NHxZYnfShorthand Story Head:
Cancer isn’t fair – but care should be
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Cancer isn’t fair – but care should be
Listening to people's lived experiences is helping to improve the awareness and uptake of cancer care.
By Louise Walsh
Over a million lives have been saved in the UK thanks to improvements in cancer prevention, diagnosis and treatment since the 1980s. But the promise of these advances is not felt by all.People can have very different experiences of cancer care because of who they are, or how and where they live.
Some individuals and communities are ‘harder-to-reach’ in terms of healthcare awareness and access. This might be because of socioeconomic, cultural or language barriers. Avoidable differences in health outcomes then arise when people miss out on screening, early diagnosis and the best treatment plan.
To mark World Cancer Day (4 February), and its campaign to make cancer care fair and equitable, we take a look at some of the ways researchers and the planned Cambridge Cancer Research Hospital are working with communities to ‘close the cancer care gap’.
Lifting language barriers Patients from minority ethnic groups and cancer experts are working to increase the uptake of genetic testing in communities where language is a barrier.Genetic testing in ovarian cancer patients is part of the toolbox that clinicians draw on to support decisions about which treatment will work best for a patient’s cancer. The technique can also identify whether or not a patient was born with a high chance of developing cancer, helping them to take steps to reduce their chance of getting cancer again, and to share the information with family members if they wish.
But there is a lower uptake of genetic testing for ovarian cancer in communities where there are language barriers and a lack of awareness of inherited cancer risks. Cultural attitudes and absence of support for non-English-speaking women can also contribute to the disparities in testing, as Dr Elaine Leung explains:
Dr Elaine Leung
Dr Elaine Leung
“Women who do not speak English as their first language often don’t have as much information about genetic testing. It’s really important to look at this because in the context of cancer that really changes survival of patients.”Leung, from the Sandwell and West Birmingham NHS Trust, co-leads an award-winning project to improve rates of genetic testing with Dr Gabriel Funingana and Professor James Brenton from Cancer Research UK (CRUK) Cambridge Centre and based in the CRUK Cambridge Institute.
The project is called DEMO (for Demonstration of Improvement for Molecular Ovarian Cancer Testing) and was funded by Ovarian Cancer Action as part of its groundbreaking programme to tackle health inequalities for women with ovarian cancer.
The DEMO team knew that 15% of women diagnosed with ovarian cancer in Birmingham are non-white and a significant proportion of these women require interpreting services, particularly among speakers of South Asian languages such as Punjabi, Urdu and Bengali.
The knock-on effects of language barriers can be profound, says Dr Marie-Lyne Alcaraz, a Programme Manager for CRUK Cambridge Centre:
“Access to information for people with cancer is of vital importance. But where there’s a language barrier there’s often a significant gap in awareness and accessibility,” says Alcaraz. “You sometimes see patients carefully tucking papers away, sometimes putting them in a box outside the house ‘out of sight’, and you know that the language barriers are too much for them to absorb the information.”
Dr Marie-Lyne Alcaraz
Dr Marie-Lyne Alcaraz
The DEMO team worked with patient groups representing people from ethnic minorities to identify the barriers and misconceptions around genetic testing. One patient recalls the first project team meeting, saying:
“I felt valued from the outset and listened to, which is key. It was a team effort alongside health professionals who were genuinely interested in communicating more effectively with their patients.”The team then developed a collection of multilingual resources on the benefits of genetic testing for ovarian cancer patients. These include accessible, freely available online films in Bengali, English, Polish, Punjabi, Romanian and Urdu [see below]
“These films will improve how patients understand the role of genetic testing. The knowledge we’ve built up in this collaboration will help patient diagnosis of ovarian cancer in the UK and also in other countries,” says Funingana:
Dr Gabriel Funingana
Dr Gabriel Funingana
“Our work [on lifting language barriers] is a step towards a healthcare future where every woman with ovarian cancer benefits from the incredible advances in genomics.” Watch the films: "What is genetic testing?"Film available in Bengali, English, Polish, Punjabi, Romanian and Urdu
What do my test results mean?"Film available in Bengali, English, Polish, Punjabi, Romanian and Urdu
Genetic testing: next stepsFilm available in Bengali, English, Polish, Punjabi and Urdu
Understanding risk Dr Kelly Fagan Robinson has worked with some of the most marginalised people in Cambridgeshire to understand their experiences of cancer and attitudes towards risk.“The current picture of cancer prevention suggests that over a third of the eligible population in England are not currently participating in cancer risk detection measures like population screening programmes,” says Robinson, a medical anthropologist.
To understand some of the reasons why, she spoke to ‘hard-to-reach’ populations during the Elusive Risks project, which she worked on with Drs Maryon McDonald and Ignacia Arteaga at the Department of Social Anthropology.
Their aim was to understand how people make sense of, and navigate, risks in their lives, a theme Robinson continues to work on through her Anthropology By Communities initiatives with ‘less-heard-from’ people.
They discovered a different attitude towards risk and care. “People living one day at a time due to social exclusion, stigma or poverty are frequently focused on immediate needs to ensure survival.
“For the people we spoke to, risk was positive, it meant stepping outside of your typical way of behaving to try to do something new that could make your life better. But care was negative – children being taken into care, experiences of incarceration, being turned away from GP receptions and so on.”
She gives the example of a rough sleeper involved in the project:
“They’d had a persistent cough and had been meaning to go and get it checked because they’d lost their grandmother and mother to cancer but, the night before, their sleeping bag had been set on fire. Their words were: “when your sleeping bag’s on fire, you can’t worry about cancer”.”For those who live without a permanent residence, maintaining contact with healthcare providers over blood tests and scans is patchy, and can be complicated by other factors.
The team came across one example when they worked with Shaynie Larwood, the Lead Nurse for the Gypsy & Traveller community in Cambridgeshire. Larwood explained that culturally strong traits can sometimes work against people: “self-reliance, importance of family, stoicism, independence, not wanting to be involved with authority… doesn’t stand them in such good stead [when it comes to healthcare].”
Efforts towards closing the cancer care gap should draw on the expertise of ‘super-locals’ like Shaynie, who have first-hand experiences of issues affecting communities, says Robinson:
Dr Kelly Fagan Robinson
Dr Kelly Fagan Robinson
“They know the ‘hard-to-reach’ people as real people, and understand their concerns. They showed us that people who were invisible in other contexts were in fact easy to reach under the right conditions.”
Realising how important it is to improve engagement between researchers and the people they serve, Robinson developed a course aimed at doing just this.
In a follow-on collaboration between Cambridge and the University of Manchester, she launched ‘Shared Risk’, a bitesize online ‘MOOC’ course aimed at helping researchers and clinicians at the CRUK Cambridge Centre to define and communicate cancer risk better.
Elusive Risks was funded by Cambridge's Early Cancer Institute at the University of Cambridge. Shared Risk is the result of an International Alliance for Early Cancer Detection Skills Exchange and Development award.
Increasing access The Cancerless project aims to eliminate the significant differences that homeless people experience when accessing health care systems.Cancer is the second most common cause of death among the homeless population, who experience a doubled rate of cancer mortality compared with adults in the general population in high-income countries.
A number of factors contribute towards this, explains Dr Julia Gawronska, a postdoctoral Research Fellow at Anglia Ruskin University:
“Health is not always the number one priority for those experiencing homelessness. They also encounter barriers when trying to access healthcare systems, which are often highly fragmented.”To tackle this, Gawronska, coordinates the Cambridge arm of a cross-European project called Cancerless, which aims to improve cancer prevention, rates of screening and early diagnosis among people experiencing homelessness. The project spans Austria, Greece, Spain and the UK and is funded by the European Union Horizon 2020 programme.
Gawronska has been working with the CRUK Cambridge Centre to deliver a series of educational workshops on cancer signs and cancer prevention. The workshops are part of the Health Navigator Intervention developed by the Cancerless team, and include support for signposting to GPs.
Through monthly educational workshops at Wintercomfort, a support hub for homeless individuals in Cambridge, the team has helped raise awareness of symptoms and looked at the barriers to accessing healthcare for people experiencing homelessness.
As the team became more visible and trusted at the hub, they found that not only has workshop attendance increased but, so far, 20% of attendees have since been referred to the Cambridge Access Clinic for further tests, with a 100% follow-up appointment rate.
“It is very rewarding seeing more people engaging in these workshops and taking steps towards improving their health.”The next step of the Cancerless project is to provide a blueprint for transforming access to screening, services and treatment for people experiencing homelessness in the UK and across Europe, with evidence-based policy recommendations and protocols.
Cambridge Cancer Research Hospital Feedback from asking people what matters to them is helping to shape the design of the Cambridge Cancer Research Hospital.Due to open on the Cambridge Biomedical Campus in 2028, the Cambridge Cancer Research Hospital will transform patient care, delivering hope and better health outcomes for people with cancer.
The new hospital brings together clinical expertise at Cambridge University Hospitals with world-class scientists across the University of Cambridge and the CRUK Cambridge Centre. It draws on the Centre’s work involving patients and the public at all stages of research – from advising on strategy, to shaping research and clinical trial proposals, to participating in clinical trials and research studies – and has its own Patient Advisory Group and Network who are using their lived experience of cancer to influence the design and facilities in the new hospital.
As plans for the hospital develop, the project is currently focusing on engaging with communities and individuals who are more likely to experience health inequalities or challenges in accessing healthcare.
Elaine Chapman, Lead Advisory Nurse and co-production lead on the Cambridge Cancer Research Hospital project explains:
“We appreciate that not everyone will want to join groups or be able to attend meetings online, so it’s been important to go out and meet people in their own localities.”Elaine Chapman
Elaine Chapman
“Through proactively building relationships with underserved groups in our region we hope to understand the challenges or barriers they have faced in accessing healthcare.”The look and feel of the hospital is important to patients, as the team discovered on a recent visit to Cambridge Central Mosque as part of the Women’s Wellness Day. When asked ‘what would help make visiting Cambridge Cancer Research Hospital comfortable for you?’, the feedback covered everything from the need for a welcoming prayer space to how the new hospital should smell.
“Patients and members of the public have been involved in the hospital planning from the blank paper stage at the very start,” adds Chapman. "Their ideas, feedback and experiences are helping to shape the new hospital to ensure it is the best it can be for anyone who may need to use it when it opens.”
If you are interested in finding out more about the new Cambridge Cancer Research Hospital and patient involvement, please visit Patients | Cambridge Cancer
How you can support Cambridge’s cancer researchPublished: 4 February 2024
With thanks to Rosie Dean (Cambridge University Hospitals NHS Foundation Trust) for reporting on Cancerless and the Cambridge Cancer Research Hospital
Image: ajijchan (iStock/Getty Images Plus)
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
TopBuilt with Shorthand { setTimeout(() => { document.querySelectorAll('#main a').forEach(link => link.classList.remove('campl-external')); }, 2050); }); //--> Summary:Listening to people's lived experiences is helping to improve the awareness and uptake of cancer care. On World Cancer Day, we take a look at some of the ways researchers are working with communities to ‘close the cancer care gap’.
Image: Affiliation (schools and institutions): Cancer Research UK Cambridge InstituteCancer Research UK Cambridge CentreDepartment of Social AnthropologyCambridge Cancer Research HospitalSchool of Clinical MedicineSchool of the Humanities and Social SciencesExternal Affiliations: Sandwell and West Birmingham NHS TrustOvarian Cancer ActionAnglia Ruskin UniversityEuropean Union Horizon 2020People (our academics and staff): Gabriel FuninganaJames BrentonMarie-Lyne AlcarazKelly Fagan RobinsonElaine ChapmanSubject (including Spotlight on ... where applicable): CancerCivic engagementinequalitylanguageovarian cancerCambridge Cancer Research HospitalhospitalpatientStoriesSection: ResearchNews type: FeaturesSuper Tags: Health and medicineSocietyShorthand Story Description/Subtitle: Listening to people's lived experiences is helping to improve the awareness and uptake of cancer care.Shorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/244281/nT3NHxZYnf/assets/6nivl2iluJ/gettyimages-1357830750_full-thumbnail.jpgScientists identify how fasting may protect against inflammation
In research published in Cell Reports, the team describes how fasting raises levels of a chemical in the blood known as arachidonic acid, which inhibits inflammation. The researchers say it may also help explain some of the beneficial effects of drugs such as aspirin.
Scientists have known for some time that our diet – particular a high calorie Western diet – can increase our risk of diseases including obesity, type 2 diabetes and heart disease, which are linked to chronic inflammation in the body.
Inflammation is our body’s natural response to injury or infection, but this process can be triggered by other mechanisms, including by the so-called ‘inflammasome’, which acts like an alarm within our body’s cells, triggering inflammation to help protect our body when it senses damage. But the inflammasome can trigger inflammation in unintentional ways – one of its functions is to destroy unwanted cells, which can result in the release of the cell’s contents into the body, where they trigger inflammation.
Professor Clare Bryant from the Department of Medicine at the University of Cambridge said: “We’re very interested in trying to understand the causes of chronic inflammation in the context of many human diseases, and in particular the role of the inflammasome.
“What's become apparent over recent years is that one inflammasome in particular – the NLRP3 inflammasome – is very important in a number of major diseases such as obesity and atherosclerosis, but also in diseases like Alzheimer's and Parkinson's disease, many of the diseases of older age people, particularly in the Western world.”
Fasting can help reduce inflammation, but the reason why has not been clear. To help answer this question, a team led by Professor Bryant and colleagues at the University of Cambridge and National Institute for Health in the USA studied blood samples from a group of 21 volunteers, who ate a 500kcal meal then fasted for 24 hours before consuming a second 500kcal meal.
The team found that restricting calorie intake increased levels of a lipid known as arachidonic acid. Lipids are molecules that play important roles in our bodies, such as storing energy and transmitting information between cells. As soon as individuals ate a meal again, levels of arachidonic acid dropped.
When the researchers studied arachidonic acid’s effect in immune cells cultured in the lab, they found that it turns down the activity of the NLRP3 inflammasome. This surprised the team as arachidonic acid was previously thought to be linked with increased levels of inflammation, not decreased.
Professor Bryant, a Fellow of Queens’ College, Cambridge, added: “This provides a potential explanation for how changing our diet – in particular by fasting – protects us from inflammation, especially the damaging form that underpins many diseases related to a Western high calorie diet.
“It’s too early to say whether fasting protects against diseases like Alzheimer's and Parkinson's disease as the effects of arachidonic acid are only short-lived, but our work adds to a growing amount of scientific literature that points to the health benefits of calorie restriction. It suggests that regular fasting over a long period could help reduce the chronic inflammation we associate with these conditions. It's certainly an attractive idea.”
The findings also hint at one mechanism whereby a high calorie diet might increase the risk of these diseases. Studies have shown that some patients that have a high fat diet have increased levels of inflammasome activity.
“There could be a yin and yang effect going on here, whereby too much of the wrong thing is increasing your inflammasome activity and too little is decreasing it,” said Professor Bryant. “Arachidonic acid could be one way in which this is happening.”
The researchers say the discovery may also offer clues to an unexpected way in which so-called non-steroidal anti-inflammatory drugs such as aspirin work. Normally, arachidonic acid is rapidly broken down in the body, but aspirin stops this process, which can lead to an increase in levels of arachidonic acid, which in turn reduce inflammasome activity and hence inflammation.
Professor Bryant said: “It’s important to stress that aspirin should not be taken to reduce risk of long terms diseases without medical guidance as it can have side-effects such as stomach bleeds if taken over a long period.”
The research was funded by Wellcome, the Medical Research Council and the US National Heart, Lung, and Blood Institute Division of Intramural Research.
Reference
Pereira, M & Liang, J et al. Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting. Cell Reports; 23 Jan 2024; DOI: 10.1016/j.celrep.2024.113700
Cambridge scientists may have discovered a new way in which fasting helps reduce inflammation – a potentially damaging side-effect of the body’s immune system that underlies a number of chronic diseases.
dietObesitytype 2 diabetesAlzheimer's diseaseParkinson's diseaseinflammationClare BryantWellcomeMedical Research CouncilSchool of Clinical MedicineDepartment of MedicineQueens' CollegeOur work adds to a growing amount of scientific literature that points to the health benefits of calorie restrictionClare BryantCarol Yepes (Getty Images)Intermittent fasting conceptual image
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