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NHS trial of sponge-on-a-string test replaces need for endoscopy for thousands of patients

5 hours 35 min ago

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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YesNews type: NewsSuper Tags: Health and medicine

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'script', document); //--> */ Shorthand Story Body:  LinkedInTwitterFacebook Improving outcomes for Crohn's patients Treating newly-diagnosed patients with advanced therapy leads to dramatic improvements in outcomes

By Craig Brierley

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

TopBuilt with Shorthand { setTimeout(() => { document.querySelectorAll('#main a').forEach(link => link.classList.remove('campl-external')); }, 2050); }); //--> Summary: 

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.jpg

Long COVID linked to persistently high levels of inflammatory protein: a potential biomarker and target for treatments

Wed, 21/02/2024 - 18:45

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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YesLicence type: AttributionNews type: NewsSuper Tags: Health and medicine

Scientists identify genes linked to DNA damage and human disease

Fri, 16/02/2024 - 10:17

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


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.

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School uniform policies linked to students getting less exercise, study finds

Thu, 15/02/2024 - 00:01

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

Mon, 12/02/2024 - 10:20

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

Tue, 06/02/2024 - 14:00

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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YesLicence type: Public DomainNews type: NewsSuper Tags: Health and medicine

Using AI to tackle society's biggest challenges

Mon, 05/02/2024 - 08:00
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'script', document); //--> */ Shorthand Story Body:  LinkedInTwitterFacebook 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.

Visit the ai@cam website

Visit the ai@cam website

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:

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 health

Brain 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 AI

The 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 AI

Using 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 creation

Public 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 nature

The 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:

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.jpg

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'script', document); //--> */ Shorthand Story Body:  LinkedInTwitterFacebook 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 steps

Film 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 research

Published: 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)

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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.jpg

Scientists identify how fasting may protect against inflammation

Tue, 30/01/2024 - 09:55

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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Removing largest wine glass serving reduces amount of wine sold in bars and pubs

Thu, 18/01/2024 - 19:00

While only modest, the finding could provide one way of nudging customers to drink less alcohol and have an impact at a population level, say the researchers.

Alcohol consumption is the fifth largest contributor to premature death and disease worldwide. In 2016 it was estimated to have caused approximately 3 million deaths worldwide.

There are many factors that influence how much we drink, from advertising to labelling to availability and cost. Previous research from the Behaviour and Health Research Unit at Cambridge has shown that even glass size can influence how much alcohol is consumed.

In research published today in PLOS Medicine, the Cambridge team carried out a study in 21 licensed premises (mainly pubs) in England to see whether removing their largest serving of wine by the glass for four weeks would have an impact on how much wine is consumed. Wine is the most commonly drunk alcoholic drink in the UK and Europe. Twenty of the premises completed the experiment as designed by the researchers and were included in the final analysis.

After adjusting for factors such as day of the week and total revenue, the researchers found that removing the largest wine glass serving led to an average (mean) decrease of 420ml of wine sold per day per venue – equating to a 7.6% decrease.

There was no evidence that sales of beer and cider increased, suggesting that people did not compensate for their reduced wine consumption by drinking more of these alcoholic drinks. There was also no evidence that it affected total daily revenues, implying that participating licensed premises did not lose money as a result of removing the largest serving size for glasses of wine, perhaps due to the higher profit margins of smaller serving sizes of wine. However, it is important to note that the study was not designed to provide statistically meaningful data on these points.

First author Dr Eleni Mantzari, from the University of Cambridge, said: “It looks like when the largest serving size of wine by the glass was unavailable, people shifted towards the smaller options, but didn’t then drink the equivalent amount of wine.

“People tend to consume a specific number of ‘units’ – in this case glasses – regardless of portion size. So, someone might decide at the outset they’ll limit themselves to a couple of glasses of wine, and with less alcohol in each glass they drink less overall.”

Professor Dame Theresa Marteau, the study’s senior author and an Honorary Fellow at Christ’s College Cambridge, added: “It’s worth remembering that no level of alcohol consumption is considered safe for health, with even light consumption contributing to the development of many cancers. Although the reduction in the amount of wine sold at each premise was relatively small, even a small reduction could make a meaningful contribution to population health.”

Evidence suggests that the public prefer information-based interventions, such as health warning labels, to reductions in serving or package sizes. However, in this study, managers at just four of the 21 premises reported receiving complaints from customers.

The researchers note that although the intervention would potentially be acceptable to pub or bar managers, given there was no evidence that it can result in a loss in revenue, a nationwide policy would likely be resisted by the alcohol industry given its potential to reduce sales of targeted drinks. Public support for such a policy would depend on its effectiveness and how clearly this was communicated.

The research was funded by Wellcome.

Reference
Mantzari, E et al. Impact on wine sales of removing the largest serving size by the glass: an A-B-A reversal trial in 21 pubs, bars and restaurants in England. PLOS Medicine; DOI: 10.1371/journal.pmed.1004313

Taking away the largest serving of wine by the glass – in most cases the 250ml option – led to an average reduction in the amount of wine sold at pubs and bars of just under 8%, new research led by a team at the University of Cambridge has discovered.

Spotlight on public healthTheresa MarteauEleni MantzariWellcomeSchool of Clinical MedicineCambridge Public HealthBehaviour and Health Research Unit (BHRU)Christ's CollegeWhen the largest serving size of wine by the glass was unavailable, people shifted towards the smaller options, but didn’t then drink the equivalent amount of wineEleni Mantzarihcdeharder (Pixabay)Red and white wine in glasses


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YesLicence type: Public DomainNews type: NewsSuper Tags: Health and medicine

‘Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders

Wed, 17/01/2024 - 16:00

The study, published today in Cell Stem Cell, shows that it is possible to experiment on a developing human placenta, rather than merely observe specimens, in order to study major disorders of pregnancy.

Successful pregnancy depends on the development of the placenta in the first few weeks of gestation. During this period, the placenta implants itself into the endometrium – the mucosal lining of the mother’s uterus.

Interactions between the cells of the endometrium and the cells of the placenta are critical to whether a pregnancy is successful. In particular, these interactions are essential to increase the maternal blood supply to the placenta, necessary for fetal growth and development.

When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby.

Professor Ashley Moffett from the Department of Pathology at the University of Cambridge said: “Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a ‘black box of human development’.

“Over the past few years, many scientists – including several at Cambridge – have developed embryo-like models to help us understand early pre-implantation development. But further development is impeded because we understand so little about the interactions between the placenta and the uterus.”

Professor Moffett and colleagues at the Friedrich Miescher Institute, Switzerland, and the Wellcome Sanger Institute, Cambridge, have used ‘mini-placentas’ – a cellular model of the early stages of the placenta – to provide a window into early pregnancy and help improve our understanding of reproductive disorders. Known as ‘trophoblast organoids’, these are grown from placenta cells and model the early placenta so closely that they have previously been shown to record a positive response on an over-the-counter pregnancy test.

In previous work, Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia. These highlighted the important role of immune cells uniquely found in the uterus, known as ‘uterine natural killer cells’, which cluster in the lining of the womb at the site where the placenta implants. These cells mediate the interactions between the endometrium and the cells of the placenta.

In their new study, her team applied proteins secreted by the uterine natural killer cells to the trophoblast organoids so that they could mimic the conditions where the placenta implants itself. They identified particular proteins that were crucial to helping the organoids develop. These proteins will contribute to successful implantation, allowing the placenta to invade the uterus and transform the mother’s arteries.

“This is the only time that we know of where a normal cell invades and transforms an artery, and these cells are coming from another individual, the baby,” said Professor Moffett, who is also a Fellow at King’s College, Cambridge.

“If the cells aren’t able to invade properly, the arteries in the womb don’t open up and so the placenta – and therefore the baby – are starved of nutrients and oxygen. That's why you get problems later on in pregnancy, when there just isn't enough blood to feed the baby and it either dies or is very tiny.”

The researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders.

Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland and co-lead of this work, added: “Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what's happening in the first few weeks.

“Using ‘mini-placentas’, we can do just that, providing clues as to how and why pre-eclampsia occurs. This has helped us unpick some of the key processes that we should now focus on far more. It shows the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.”

The research was supported by Wellcome, the Royal Society, European Research Council and Medical Research Council.

Reference
Li, Q et al. Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy. Cell Stem Cell; 17 Jan 2024; DOI: doi.org/10.1016/j.stem.2023.12.013

Scientists have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb – findings that could help scientists better understand and, in future, potentially treat pre-eclampsia.

ReproductionStem cellsAshley MoffettWellcomeRoyal SocietyEuropean Research CouncilMedical Research CouncilSchool of the Biological SciencesDepartment of PathologyCambridge Reproduction Strategic Research InitiativeKing's CollegeMost of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study.Ashley MoffettFriedrich Miescher Institute/University of CambridgePlacental organoid (circle in the centre). Trophoblast cells are invading out of the organoid, mimicking placental cells invading the uterus in the early weeks of pregnancy.


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Role of inherited genetic variants in rare blood cancer uncovered

Wed, 17/01/2024 - 10:03

Large-scale genetic analysis has helped researchers uncover the interplay between cancer-driving genetic mutations and inherited genetic variants in a rare type of blood cancer.

Researchers from the University of Cambridge, Wellcome Sanger Institute, and collaborators, combined various comprehensive data sets to understand the impact of both cancer-driving spontaneous mutations and inherited genetic variation on the risk of developing myeloproliferative neoplasms (MPN).

The study, published today in the journal Nature Genetics, describes how inherited genetic variants can influence whether a spontaneous mutation in a particular gene increases the risk of developing this rare blood cancer.

This analysis has an impact on current clinical predictions of disease development in individuals. Further research is required to understand the biological mechanisms behind how these inherited genetic variants influence the chances of developing rare blood cancer. In the future, this knowledge could aid drug development and interventions that reduce the risk of disease.

Myeloproliferative neoplasms, MPNs, are a group of rare, chronic, blood cancers. There are around 4,000 cases of MPN in the UK each year. These occur when the bone marrow overproduces blood cells, which can result in blood clots and bleeding. MPNs can also progress into other forms of blood cancer, such as leukaemia.

In the population, there is a large amount of natural variation between individuals’ blood cells, which can affect the amount of blood cells a person has and their particular traits. This is because multiple different genes can influence blood cell features in an individual. During routine blood tests, researchers take known information about these genes and analyse the variation to give a genetic risk score, which is how likely that individual is to develop a disease over their lifetime.  

MPNs have been linked to random somatic mutations in certain genes including in a gene called JAK2. However, mutated JAK2 is commonly found in the global population, and the vast majority of these individuals do not have or go on to develop MPN.

Whilst previous studies have identified over a dozen associated inherited genetic variants that increase the risk of MPN, these studies insufficiently explain why most individuals in the population do not go on to develop MPN.

This new study, from the Wellcome Sanger Institute and collaborators, combined information on the known somatic driver mutations in MPN, inherited genetic variants, and genetic risk scores from individuals with MPN.

They found that the inherited variants that cause natural blood cell variation in the population also impact whether a JAK2 somatic mutation will go on to cause MPN.  They also found that individuals with an inherited risk of having a higher blood cell count could display MPN features in the absence of cancer-driving mutations, thus, mimicking disease.

Dr Jing Guo, from the University of Cambridge and the Wellcome Sanger Institute and first author of the study, said: “Our large-scale statistical study has helped fill the knowledge gaps in how variants in DNA, both inherited and somatic, interact to influence complex disease risk. By combining these three different types of datasets we were able to get a more complete picture of how these variants combine to cause blood disorders.”

Professor Nicole Soranzo, co-senior author from the University of Cambridge, the Wellcome Sanger Institute, and Human Technopole, Italy, said: “There has been increasing realisation that human diseases have complex causes involving a combination of common and rare inherited genetic variants with different severity.

“We have previously shown that variation in blood cell parameters and function has complex genetic variability by highlighting thousands of genetic changes that affect different gene functions. Here, we show for the first time that common variants in these genes also affect blood cancers, independent of causative somatic mutations. This confirms a new important contribution of normal variability beyond complex disease, contributing to our understanding of myeloproliferative neoplasms and blood cancer more generally.”

Dr Jyoti Nangalia, co-senior author from the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge, and the Wellcome Sanger Institute, said: “We have a good understanding of the genetic causes of myeloproliferative neoplasms. In fact, many of these genetic mutations are routine diagnostic tests in the clinic. However, these mutations can often be found in healthy individuals without the disease.

“Our study helps us understand how inherited DNA variation from person to person can interact with cancer-causing mutations to determine whether disease occurs in the first place, and how this can alter the type of any subsequent disease that emerges. Our hope is that this information can be incorporated into future disease prediction efforts.”  

This research was funded by Cancer Research UK and Wellcome.

Reference

J. Guo, K. Walter, P. M. Quiros, et al. ‘Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.’ Jan 2024,  Nature Genetics. DOI: 10.1038/s41588-023-01638-x

Adapted from a press release by the Wellcome Sanger Institute

Combining three different sources of genetic information has allowed researchers to further understand why only some people with a common mutation go on to develop rare blood cancer

blood cancerCancerEngineeringJing GuoNicole SoranzoJyoti NangaliaWellcome Sanger InstituteDepartment of EngineeringDepartment of HaematologySchool of TechnologySchool of Clinical MedicineWellcome-MRC Cambridge Stem Cell InstituteOur hope is that this information can be incorporated into future disease prediction effortsJyoti NangaliaPhoto by Sangharsh Lohakare on UnsplashDNA


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YesLicence type: Attribution-NoncommericalNews type: NewsSuper Tags: Health and medicineScience

Significant gaps in COVID-19 vaccine uptake may have led to over 7,000 hospitalisations and deaths

Mon, 15/01/2024 - 23:30

The findings, published today in The Lancet, suggest that more than 7,000 hospitalisations and deaths might have been averted in summer 2022 if the UK had had better vaccine coverage.

With COVID-19 cases on the rise and a new variant strain recently identified, this research provides a timely insight into vaccine uptake and hesitancy and could inform policy-makers.

The research relied on secure access to anonymised health data for everyone in all four nations of the UK, an advance which has only become possible during the pandemic.

Co-author Angela Wood, Professor of Health Data Science at the Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge and Associate Director of the British Heart Foundation Data Science Centre said: “This is the first epidemiological study to use individual-level anonymised health data covering the entire UK population. We have created a detailed, UK-wide picture of who is under-vaccinated against COVID-19 and the associated risks of under-vaccination.

“These results can be used to help create health policy and public health interventions to improve vaccine uptake. This approach could be extended to many other areas of medicine with great potential for new discoveries in the understanding and treatment of disease.”

Early COVID-19 vaccine rollout began strongly in the UK, with over 90% of the population over the age of 12 vaccinated with at least one dose by January 2022. However, rates of subsequent booster doses across the UK were not fully understood until now.

Scientists from England, Scotland, Northern Ireland and Wales – led by Health Data Research UK (HDR UK) and the University of Edinburgh – studied securely-held, routinely collected NHS data from everyone over five years of age during 1 June to 30 September 2022. All data was de-identified and available only to approved researchers.

Data from across the four countries was then pooled and harmonised, a feat that was not possible until now. People were grouped by vaccine status, with under-vaccination defined as not having had all doses of a vaccine for which that a person was eligible.

The findings reveal that the proportion of people who were under-vaccinated on 1 June 2022 ranged between one third and one half of the population – 45.7% for England, 49.8% for Northern Ireland, 34.2% for Scotland and 32.8% Wales.

Mathematical modelling indicated that 7,180 hospitalisations and deaths out of around 40,400 severe COVID-19 outcomes during four months in summer 2022 might have been averted, if the UK population was fully vaccinated.

Under-vaccination was related to significantly more hospitalisations and deaths across all age groups studied, with under-vaccinated people over 75 more than twice as likely to have a severe COVID-19 outcome than those who were fully protected.

The highest rates of under-vaccination were found in younger people, men, people in areas of higher deprivation, and people of non-white ethnicity.

Researchers say the study – the largest ever study carried out in the UK – also ushers in a new era for UK science by overcoming challenges in uniting NHS data that is gathered and stored in different ways between devolved nations.

Professor Cathie Sudlow, Chief Scientist at Health Data Research UK and Director of the British Heart Foundation (BHF) Data Science Centre, said: “The infrastructure now exists to make full use of the potential of routinely collected data in the NHS across the four nations of the UK. We believe that we could and should extend these approaches to many other areas of medicine, such as cancer, heart disease and diabetes to search for better understanding, prevention and treatment of disease."

Professor Sir Aziz Sheikh, Director of the Usher Institute at the University of Edinburgh, HDR UK Research Director and study co-lead, said: “Large-scale data studies have been critical to pandemic management, allowing scientists to make policy-relevant findings at speed. COVID-19 vaccines save lives. As new variants emerge, this study will help to pinpoint groups of our society and areas of the country where public health campaigns should be focused and tailored for those communities.”

Reference
HDR UK COALESCE Consortium. Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales. Lancet; 16 Jan 2024; DOI: 0.1016/S0140-6736(23)02622-3

Adapted from a release from HDR-UK

Between a third and a half of the populations of the four UK nations had not had the recommended number of COVID vaccinations and boosters by summer 2022, according to the first research study to look at COVID-19 vaccine coverage of the entire UK population.

COVID-19vaccinationAngela WoodHealth Data Research UKUniversity of EdinburghSchool of Clinical MedicineVictor Phillip Dahdaleh Heart and Lung Research InstituteThese results can be used to help create health policy and public health interventions to improve vaccine uptakeAngela WoodKoldoyChris (Getty Images)Girl being injected with COVID-19 vaccine


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YesNews type: NewsSuper Tags: Health and medicine

Feeling depressed linked to short-term increase in bodyweight among people with overweight or obesity

Wed, 10/01/2024 - 19:00

The study, published today in PLOS ONE, found that the increase was only seen among people with overweight or obesity, but found no link between generally having greater symptoms of depression and higher bodyweight.

Research has suggested a connection between weight and mental health – with each potentially influencing the other – but the relationship is complex and remains poorly understood, particularly in relation to how changes in an individual’s mental health influence their bodyweight over time.

To help answer this question, researchers at Cambridge’s Medical Research Council (MRC) Epidemiology Unit examined data from over 2,000 adults living in Cambridgeshire, UK, who had been recruited to the Fenland COVID-19 Study.

Participants completed digital questionnaires on mental wellbeing and bodyweight every month for up to nine months during the COVID-19 pandemic (August 2020 – April 2021) using a mobile app developed by Huma Therapeutics Limited.

Questions assessed an individual’s symptoms of depression, anxiety and perceived stress. A higher score indicated greater severity, with the maximum possible scores being 24 for depression, 21 for anxiety and 40 for stress. The team then used statistical modelling to explore whether having poorer mental wellbeing than usual was related to changes in bodyweight one month later.

The researchers found that for every increment increase in an individual’s usual score for depressive symptoms, their subsequent weight one month later increased by 45g. This may seem small but would mean, for example, that in an individual whose depressive symptoms score rose from five to 10 (equal to an increase from ‘mild’ to ‘moderate’ depressive symptoms) it would relate to an average weight gain of 225g (0.225kg).

This effect was only observed in those individuals with overweight (defined as BMI 25-29.9kg/m2) or with obesity (BMI of over 30kg/m2). Individuals with overweight had on average an increase of 52g for each increment point increase from their usual depressive symptoms score and for those with obesity the comparable weight gain was 71g. The effect was not seen in those individuals with a healthy weight.

First author Dr Julia Mueller from the MRC Epidemiology Unit said: “Overall, this suggests that individuals with overweight or obesity are more vulnerable to weight gain in response to feeling more depressed. Although the weight gain was relatively small, even small weight changes occurring over short periods of time can lead to larger weight changes in the long-term, particularly among those with overweight and obesity.

“People with a high BMI are already at greater risk from other health conditions, so this could potentially lead to a further deterioration in their health. Monitoring and addressing depressive symptoms in individuals with overweight or obesity could help prevent further weight gain and be beneficial to both their mental and physical health.”

The researchers found no evidence that perceived stress or anxiety were related to changes in weight.

Senior author Dr Kirsten Rennie from the MRC Epidemiology Unit said: “Apps on our phones make it possible for people to answer short questions at home more frequently and over extended periods of time, which provides much more information about their wellbeing. This technology could help us understand how changes in mental health influence behaviour among people with overweight or obesity and offer ways to develop timely interventions when needed.”

Although previous studies have suggested that poor mental health is both a cause and consequence of obesity, the research team found no evidence that weight predicted subsequent symptoms of depression.

The research was supported by the Medical Research Council.

Reference
Mueller, J et al. The relationship of within-individual and between-individual variation in mental health with bodyweight: An exploratory longitudinal study. PLOS ONE; 10 Jan 2024; DOI: 10.1371/journal.pone.0295117

Increases in symptoms of depression are associated with a subsequent increase in bodyweight when measured one month later, new research from the University of Cambridge has found.

Mental healthdepressionObesityPublic healthJulia MellerKirsten RennieMedical Research CouncilSchool of Clinical MedicineMedical Research Council (MRC) Epidemiology Uniti yunmaiPerson standing on white digital bathroom scale


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New trial of 'pill-on-a-thread' brings screening for oesophageal cancer closer

Tue, 09/01/2024 - 08:53

The capsule sponge, known as the pill-on-a-thread, is a quick and simple test for Barrett’s oesophagus, a condition that can be a precursor to cancer. Heartburn is a common symptom of Barrett’s oesophagus, a changing of cells in the food pipe.  

The BEST4 trial launched at Addenbrooke’s Hospital today is the final step to see if the capsule sponge can prevent oesophageal cancer when used to screen or monitor those most at risk of the disease. If so, it could become a national screening programme across the NHS, in the same way mammograms are used to screen for breast cancer.

The first stage of the trial, BEST4 Surveillance, is for people already diagnosed with Barrett’s oesophagus. It will look at whether the capsule sponge test could replace endoscopies to monitor their condition. Participants will receive both examinations during the trial with results used to assess their risk of developing oesophageal cancer. 

The second stage of the trial, BEST4 Screening, opens in the summer and will recruit 120,000 people aged over 55 on long-term treatment for heartburn.

The multi-million-pound trial is jointly funded by Cancer Research UK and the National Institute for Health and Care Research. It builds on decades of research led by Professor Rebecca Fitzgerald from the University of Cambridge. She and a team of scientists, clinicians and nurses at the Early Cancer Institute, University of Cambridge and Cancer Research UK Cambridge Centre, invented and refined the capsule sponge test.

Professor Fitzgerald said: “The capsule sponge, a quick and simple test for Barrett’s oesophagus, could halve the number of deaths from oesophageal cancer every year. Cases of oesophageal cancer have increased six fold since the 1990s.  On average only 12% of patients live more than five years after diagnosis. Most don’t realise there’s a problem until they have trouble swallowing. By then it is too late.

“The first phase of the trial looks at whether the capsule sponge can be used as a cancer early warning system for patients diagnosed with Barrett’s. Using the capsule sponge and a new set of lab tests, we will be monitoring patients to see if we can prevent more cases of cancer.”

Tim Cowper, 49, a brewer from Cambridge, has had acid reflux, or heartburn, every night since he was 16. A routine health check while he was at university resulted in the shock diagnosis of Barrett’s oesophagus. After his diagnosis, he has been monitored ever since.

Tim said: “I was alarmed when I was told that having Barrett’s meant having pre-cancerous cells in my gullet. Cancer is never a nice word to hear, especially when you are so young, but luckily, I’ve had my condition monitored.

“Since my diagnosis, I’ve been going for an endoscopy at least once every three years to monitor my oesophagus. It is not pleasant at all. Each time I have a thick tube pushed down through my mouth and I can feel every single one of the biopsies taken by the camera. Swallowing a capsule sponge is a much better experience and I now get the test before my regular endoscopy appointment.”

Barrett’s oesophagus is currently identified via an endoscopy and a biopsy in hospital following a GP referral. It is time-consuming, unpleasant, and quite invasive for patients, as well as being expensive for the healthcare system.

The capsule sponge is a small, easy to swallow capsule on a thread, which contains a sponge. The patient swallows the capsule which dissolves in the stomach and the sponge expands to the size of a 50p coin.

The sponge is carefully pulled back up using the string, collecting cells for laboratory testing. The test takes just 10 minutes and can be done in a GP surgery.

Cancer Research UK and others have funded several successful clinical trials to demonstrate that the test is safe, accurate and can detect 10 times more cases of Barrett’s oesophagus than standard practice.

The test is faster and cheaper than endoscopy, which is currently used to diagnose and monitor Barrett’s oesophagus and oesophageal cancer. It has been piloted in health services in England, Scotland and Northern Ireland for patients who are currently on waiting lists for endoscopy because they have long-term heartburn or diagnosed with Barrett’s oesophagus.

Executive Director of Research and Innovation at Cancer Research UK, Dr Iain Foulkes, said: “Around 59% of all oesophageal cancer cases are preventable. Yet endoscopy, the gold standard for diagnosing and treating this cancer, is labour-intensive. We need better tools and tests to monitor people most at risk.

“Backed by funding from Cancer Research UK, the capsule sponge has become one of the most exciting early detection tools to emerge in recent years. It’s a remarkable invention by Professor Fitzgerald and her team, and previous trials have shown how powerful it can be in identifying cancer earlier.

“There are 9,200 people diagnosed with oesophageal cancer in the UK every year and the capsule sponge will mean they can benefit from kinder treatment options, if their cancer is caught at a much earlier stage.”

The future Cambridge Cancer Research Hospital will bring together clinical and research expertise, including Professor Fitzgerald’s work, under one roof.  It will enable the development and discovery of more non-invasive devices like the capsule sponge, to detect cancer earlier, and save more lives.

The BEST4 Surveillance Trial is led from Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, with trial design, coordination and analysis of results by the Cancer Research UK Cancer Prevention Trials Unit at Queen Mary University of London.

Further information about the BEST4 trial.

Adapted from a press release from Cambridge University Hospitals NHS Foundation Trust

A man from Cambridge is the first to join the surveillance part of a clinical trial that could see routine screening for oesophageal cancer introduced into the NHS, potentially halving deaths from this cancer every year.

CancerRebecca FitzgeraldCancer Research UK (CRUK)School of Clinical MedicineCambridge Cancer CentreEarly Cancer InstituteCambridge University Hospitals NHS Foundation TrustThe capsule sponge, a quick and simple test for Barrett’s oesophagus, could halve the number of deaths from oesophageal cancer every yearRebecca Fitzgerald


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Spanish butterflies better at regulating their body temperature than their British cousins

Tue, 09/01/2024 - 04:32
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'script', document); //--> */ Shorthand Story Body:  LinkedInTwitterFacebook Spanish butterflies better at regulating their body temperature than their British cousins

By Sarah Collins
Published 9 January 2024

Small copper butterfly. Credit: Andrew Bladon

Small copper butterfly. Credit: Andrew Bladon

Butterfly populations in Catalonia in northern Spain are better than their UK counterparts at regulating their body temperature by basking in the sunshine, but rising global temperatures due to climate change may put Spanish butterflies at greater risk of extinction.

An international study, led by the University of Cambridge and the Institut de Biologia Evolutiva (IBE) in Barcelona, found that butterflies use different methods to regulate their body temperature. In Catalonia, butterflies tend to angle their wings towards the sun to warm up at lower temperatures, while British butterflies rely more on finding warm microclimates.

However, as local temperatures rise, both populations switch to heat-avoiding behaviour. And as global temperatures rise, British butterflies may initially benefit, while Spanish butterflies may not be able to survive if they are not able to adapt quickly enough.

However, habitat loss, particularly in the UK, is an equally important threat to butterflies. Diverse habitats offer butterflies a greater variety of microclimates, and initiatives such as ‘no-mow May’, allowing wildflowers to grow along roadsides, and planting more trees can help counter habitat loss. The results are reported in the Journal of Animal Ecology.

Like all insects, butterflies are ‘cold-blooded’ and use their environment to regulate their internal temperature. Understanding how butterflies thermoregulate is important for predicting which species are most at risk from the effects of climate change.

In a study published in 2020, several of the same researchers showed that there are significant variations in the ability of different UK butterfly species to maintain a suitable body temperature. Species that rely mostly on shade to keep cool are at greatest risk of population decline, due to climate change and habitat loss.

“The first study in the UK showed that butterflies are pretty good at regulating their body temperature in this cooler climate, but we wanted to see whether butterflies in a warmer climate, such as Spain, are doing anything differently,” said lead author Eric Toro-Delgado from IBE, a joint centre of the Consejo Superior de Investigaciones Científicas (CSIC) and Universitat Pompeu Fabra (UPF), “And if there are differences, what mechanisms might be driving it?”

“In Spain, butterflies spend much more time at their optimum temperature since it’s warmer, but there’s also a greater risk of overheating,” said Dr Andrew Bladon from Cambridge’s Department of Zoology, the study’s senior author. “We wanted to see whether the results we got from our UK data would be repeatable in a different environment.”

For the current study, the researchers collected similar data as the 2020 UK paper, but from butterflies in Catalonia. They measured body temperature, air temperature, and perch temperature for almost 800 adult butterflies from 23 different species: for ten of these species, the researchers had comparable data from the UK.

“We hypothesised that Spanish butterflies might show adaptations to their warmer climate, which could give us an indication of how British butterflies might need to adapt to cope with climate change,” said Bladon.

The researchers found that on a community level, butterflies in Catalonia were better at regulating, or buffering, their body temperature than British butterflies. Butterflies in both countries switch from heat-seeking to heat-avoiding behaviour once air temperatures reach approximately 22°C. However, the communities differ in the use of buffering mechanisms, with British populations depending more on microclimates for thermoregulation compared to Catalan populations.

Many landscapes in the UK do not provide a sufficient diversity of thermal environments, with alternating areas of shade and sun. For UK butterflies that rely on microclimates to regulate body temperature, habitat and biodiversity loss is a major threat. In Catalonia, one of the reasons why butterflies are better at regulating their temperature could be because butterflies have many more thermal options available to them.

“In the UK, many of our nature reserves are like islands, with little variety in between,” said Bladon. “If we can provide them with field margins, biodiverse road verges, more wildflowers, and longer grass, butterflies can more easily move through the landscape, helping them find their preferred temperatures so they can thrive.”

Although Catalan butterfly populations seem to be able to thermoregulate successfully at present, rising global temperatures due to climate change put them at greater risk, since it is so warm in Spain already.

“In the UK study, the Cambridge team found that wing size was related to the ability of a species to regulate its body temperature, and that species with large wings were better at it,” said Toro-Delgado. “We expected to find a similar result in Spain, but we didn’t. This is likely because in a warm country like Spain, the ability to avoid heat is preferable, and wings may play a less relevant role in this than in warming up.”

“Because of rising global temperatures, the UK’s climate is becoming a little bit more like Spain, so climate change may benefit British butterflies in the short term,” said Bladon. “But what’s striking is butterflies in both countries showed signs of heat avoidance. And the Catalan butterflies are at greater risk since they are already near their thermal optimum.”

The researchers say that beyond rising temperatures, butterflies are also at risk from associated climate impacts, such as droughts or heatwaves. These extreme weather events can not only push butterflies past their thermal limits, but they can kill the plants that their caterpillars rely on.

“Climate change is a two-pronged attack that can take out both adult butterflies and their caterpillars,” said Toro-Delgado. “Climate change and biodiversity loss go hand-in-hand, and we urgently need to address both if we’re going to protect important species like butterflies.”

The research was supported in part by the Spanish National Research Council, the Isaac Newton Trust, Wellcome, Generalitat de Catalunya, the Spanish Ministry of Science, Innovation and Universities, the UK Natural Environment Research Council, and the European Social Fund Plus.

Reference:
E. Toro-Delgado et al. ‘Regional differences in thermoregulation between two European butterfly communities.’ Journal of Animal Ecology (2024). DOI: 10.1111/1365-2656.14039

All photographs credit: Andrew Bladon
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Small copper butterfly
Swallowtail butterfly
Iberian marbled white butterfly
Speckled wood butterfly
Red admiral butterfly

The text in this work is licensed under a Creative Commons Attribution 4.0 International License

TopBuilt with Shorthand { setTimeout(() => { document.querySelectorAll('#main a').forEach(link => link.classList.remove('campl-external')); }, 2050); }); //--> Summary: 

Butterfly populations in northern Spain are better than their UK counterparts at regulating their body temperature, but rising global temperatures may put Spanish butterflies at greater risk of extinction.

Image: Affiliation (schools and institutions): Department of ZoologySchool of the Biological SciencesMagdalene CollegeExternal Affiliations: Institut de Biologia EvolutivaIsaac Newton TrustWellcomeNatural Environment Research Council (NERC)People (our academics and staff): Andrew BladonSubject (including Spotlight on ... where applicable): butterflyinsectsClimate changeanimalanimal behaviourSpainBody temperatureEnvironmentSection: ResearchSuper Tags: EnvironmentShorthand Story Description/Subtitle: Spanish butterflies better at regulating body temperature than their UK cousinsShorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/243951/Ibjt1Xyvp9/assets/PNkivb1njO/img_4379-small-copper-ls-thumbnail.jpg

Reducing inequality is essential in tackling climate crisis, researchers argue

Tue, 02/01/2024 - 10:32

In a report just published in the journal Nature Climate Change, researchers argue that tackling inequality is vital in moving the world towards Net-Zero – because inequality constrains who can feasibly adopt low-carbon behaviours.

They say that changes are needed across society if we are to mitigate climate change effectively. Although wealthy people have very large carbon footprints, they often have the means to reduce their carbon footprint more easily than those on lower incomes.

The researchers say there is lack of political recognition of the barriers that can make it difficult for people to change to more climate-friendly behaviours.

They suggest that policymakers provide equal opportunities for low-carbon behaviours across all income brackets of society.

The report defines inequality in various ways: in terms of wealth and income, political influence, free time, and access to low-carbon options such as public transport and housing insulation subsidies.

“It’s increasingly acknowledged that there’s inequality in terms of who causes climate change and who suffers the consequences, but there’s far less attention being paid to the effect of inequality in changing behaviours to reduce carbon emissions,” said Dr Charlotte Kukowski, a postdoctoral researcher in the University of Cambridge Departments of Psychology and Zoology, and first author of the report.

She added: “People on lower incomes can be more restricted in the things they can do to help reduce their carbon footprint, in terms of the cost and time associated with doing things differently.”

The researchers found that deep-rooted inequalities can restrict people’s capacity to switch to lower-carbon behaviours in many ways. For example:

Insulating a house in the UK can be costly, and government subsidies are generally only available for homeowners; renters have little control over the houses they live in.

The UK has large numbers of old, badly insulated houses that require more energy to heat than new-build homes. The researchers call for appropriate government schemes that make it more feasible for people in lower income groups to reduce the carbon emissions of their home.

Cooking more meat-free meals: plant-based meat alternatives currently tend to be less affordable than the animal products they are trying to replace.

Eating more plant-based foods instead of meat and animal-derived products is one of the most effective changes an individual can make in reducing their carbon footprint.

Buying an electric car or an electric bike is a substantial upfront cost, and people who aren’t in permanent employment often can’t benefit from tax breaks or financing available through employer schemes.

Other low-carbon transport options - such as using public transport instead of a private car - are made less feasible for many due to poor services, particularly in rural areas.

Sometimes the lower-carbon options are more expensive - and this makes them less accessible to people on lower incomes.

“If you have more money you're likely to cause more carbon emissions, but you're also more likely to have greater ability to change the things you do and reduce those emissions,” said Dr Emma Garnett, a postdoctoral researcher at the University of Oxford and second author of the report.

She added: “Interventions targeting high-emitting individuals are urgently needed, but also many areas where there are lower-carbon choices - like food and transport - need everyone to be involved.”

The researchers say that campaigns to encourage people to switch to lower-carbon behaviours have tended to focus on providing information. While this is important in helping people understand the issues, there can still be many barriers to making changes.

They suggest a range of policy interventions, such as urban planning to include bus and bike lanes and pedestrian-friendly routes, progressive taxation rates on wealth and income, and employer-subsidised low-carbon meal options.

The research was funded by the Swiss National Science Foundation and Wellcome.

Reference: Kukowski, C.A. & Garnett, E.E.: ‘Tackling Inequality is Essential for Behaviour Change for Net Zero.’ Nature Climate Change, December 2023. DOI: 10.1038/s41558-023-01900-4

Promoting climate-friendly behaviours will be more successful in societies where everyone has the capacity: financially, physically, and timewise, to make changes.

EnvironmentClimate changeCharlotte KukowskiOxford UniversityDepartment of PsychologyDepartment of ZoologyCambridge Conservation InitiativeUniversity of Cambridge Conservation Research Institute (UCCRI)School of the Biological SciencesPeople on lower incomes can be more restricted in the things they can do to help reduce their carbon footprint.Charlotte KukowskiRgStudio / GettyBusinesswoman commuting on electric bike


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 – as here, 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.

YesLicence type: AttributionNews type: NewsSuper Tags: EnvironmentSociety

Ageing: can we add more life to our years?

Wed, 20/12/2023 - 08:59
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'script', document); //--> Shorthand Story Body:  TwitterFacebook Can we add more life to our years? Research advances at the University of Cambridge mean that the eternal quest to reverse the march of time may soon become a reality

By Jacqueline Garget

Older man skydiving. Credit Hans Berggren/ Getty.

Older man skydiving. Credit Hans Berggren/ Getty.

We’re living longer than ever before.

In 1841, UK life expectancy at birth was roughly 40 years - now it’s around 81. But longevity does not always equate to good health - there’s a discrepancy between lifespan: the number of years we live, and healthspan: the number of those years we live in good health.

From the age of 60, at least half of us will start to develop an age-related condition. And once one appears, more will often follow. With care systems already overwhelmed, what if we could target the causes of age-related decline, and reverse them?

4000 dots represent the average human lifespan of 4000 weeks. But not all weeks are equal. As we age, our risk of diseases such as cancer, arthritis, dementia and stroke greatly increases - represented here by colour change from top left to bottom right. Credit: Alex Cagan.

4000 dots represent the average human lifespan of 4000 weeks. But not all weeks are equal. As we age, our risk of diseases such as cancer, arthritis, dementia and stroke greatly increases - represented here by colour change from top left to bottom right. Credit: Alex Cagan.

Why do we age?

Credit: Mindful Media/ Getty

Credit: Mindful Media/ Getty

Despite the fact that ageing affects almost every living organism, scientists don’t fully understand what causes it. This is an obvious first step if we want to slow down, or even prevent, its effects.

“Our bodies undergo lots of biological changes as we age, but it’s not really clear which of those are consequences of ageing, and which of those are actually causing it.”

Dr Alex Cagan, Department of Genetics

One potential contributor to ageing is the gradual accumulation of mutations in our cells’ DNA – which provides instructions for our bodies to function. This could ultimately lead to disease and the visible features of ageing.

Our DNA is constantly barraged with damage by the everyday processes going on in our cells. Sometimes mistakes are made when DNA is repaired, or copied as cells replicate. And external factors like smoking, UV rays from the sun, and pollutants, also cause damage.

Cagan is trying to unlock the secrets of how some species can live so long, by comparing mutational processes in the DNA of long- and short-lived species.

“All the species we’ve looked at get to the end their lives with a similar number of DNA mutations - from mice that live about three years, to humans that live about 80 years,” he says. “This suggests there’s an evolutionary constraint to how many mutations an organism can accumulate.”

Mice live for around three years, while Bowhead Whales can live for over 200. Credit: Alex Cagan.

Mice live for around three years, while Bowhead Whales can live for over 200. Credit: Alex Cagan.

He plans to explore whether animals with very long life-spans - like whales, elephants, and ‘immortal jellyfish’ - have evolved a better ability to repair their DNA damage than we do. If we can understand what’s going on in their cells, maybe we could transfer that process into humans.

Cancer risk

DNA. Credit: ANIRUDH on Unsplash

DNA. Credit: ANIRUDH on Unsplash

One particularly fascinating long-lived species is the naked mole-rat. Based on its mouse-like size, it would be expected to live for three to five years - but it actually lives for over 30. Naked mole-rats age healthily too, and seem particularly resistant to cancer.

Naked mole-rat. Credit: GlobalP/iStock.

Naked mole-rat. Credit: GlobalP/iStock.

“Naked mole-rats live a long time, and as mammals they’re more closely related to humans than other long-lived species we know about like certain species of bird,” says Professor Ewan St. John Smith in the Department of Pharmacology, who keeps five colonies of naked mole-rats in Cambridge.

Large species have more cells, so in theory should get cancer more often than smaller species – but this isn’t the case. Some large whale species, for example, have quadrillions of cells, but if their risk of cancer per cell was the same as humans, they wouldn’t even reach their first birthday without developing it.

“This suggests whales must have better mechanisms of cancer resistance than humans,” says Cagan. “It’s possible that whatever they're doing to resist ageing - some can live to 200 years old - is also what's making them less likely to get cancer."

He adds: "If mutations to DNA cause both ageing and cancer, then reducing the mutation rate by having more accurate DNA damage responses would potentially solve both problems at once.”

“If we’re going to understand the puzzles of ageing, I think there’s a lot to be learned from studying the extreme biology and extended healthspan of naked mole-rats.”

Ewan St. John Smith, Department of Pharmacology

“Ageing is a major risk factor for most forms of cancer,” adds St. John Smith. “Our cells accumulate mutations over time, so the longer we live, the more likely we are to develop cancer."

"We’re trying to understand what enables the naked mole-rats to be cancer resistant, in the hope it will provide insights to help us prevent cancer - or treat it more effectively - in humans."

Dementia risk

Photo by Priyanka Singh on Unsplash

Photo by Priyanka Singh on Unsplash

DNA mutations are also thought to play a role in some types of neurodegenerationanother group of conditions associated with ageing including Alzheimer’s and Parkinson’s’ diseases.

Dr Janet Kumita in the University’s Department of Pharmacology is investigating how proteins misfold and form clumps - called aggregates - in the brain, the hallmark of many forms of dementia.

“I’m trying to discover how the youthful body deals with protein aggregates, to see if we can put those mechanisms to work again in older age to keep the body healthy.” Janet Kumita, Department of Pharmacology

“Protein aggregation is a very time-dependent process," she says. "In terms of a human lifespan, it takes a while for a single protein to bump into its neighbours and form the first clumps, but once that happens it’s easier for the clumps to get bigger and bigger. That’s why most neurodegenerative diseases are linked to ageing.”

The body has systems in place to identify misfolded proteins and get rid of them, but with age these systems stop working properly and more aggregates form, with debilitating effects on the brain. “In theory, if you can target the misfolded proteins, you could get rid of them before they cause problems,” says Kumita.

“When patients are showing symptoms and being diagnosed with Parkinson's or Alzheimer’s, these pathological aggregates are often already forming. If we could diagnose patients very early on, we’d have a better chance of preventing aggregation and the progression of dementia.”

Kumita has started identifying specific protein aggregates that form in the brain (there are many different configurations and sizes) and is testing ways to target and destroy them.

She’s learned a lot from experiments in test tubes and now wants to see how the process works inside body cells, where many other things are happening in tandem. That’s where the naked mole-rats come in: their brains seem to stay healthy throughout life (they usually only die because another animal kills them in a fight).

“There’s very little evidence that naked mole-rats develop protein aggregates or get neurodegenerative diseases,” says Kumita. “By looking at what’s happening in their cells to prevent these diseases, we hope to find clues to what’s going wrong in human cells – and maybe we can recreate in humans whatever the naked mole-rats are doing.”

Total rewind?

Time fading. Credit BOTCookie/Getty.

Time fading. Credit BOTCookie/Getty.

Dr Delphine Larrieu is trying to understand ageing from a different angle – by investigating the premature ageing condition, progeria syndrome.

This very rare disease affects around 400 children worldwide at any time, who start developing the signs of ageing at just a few years old. By 14, their bodies are like 80 year-olds with wrinkled skin, stiff joints, and cardiovascular disease that is usually the cause of their very early death.

Two girls, aged 9 and 10, with progeria syndrome. Photo courtesy of The Progeria Research Foundation.

Two girls, aged 9 and 10, with progeria syndrome. Photo courtesy of The Progeria Research Foundation.

Progeria syndrome is caused by a mutation that affects the structure of the nuclear envelope – an important component of body cells which, amongst other functions, protects the DNA from damage.

“What’s interesting is that nuclear envelope dysfunction also occurs to some extent during normal ageing. So some of the cells of people who are 80-90 years old look similar to the cells of progeria patients,” says Larrieu, in the Department of Pharmacology.

“In my lab we’re trying to understand whether the mechanisms behind this are the same – both to find new treatments for progeria patients and also to learn more about what’s happening during normal ageing.”

In an incredible breakthrough Larrieu has identified genes which, when ‘knocked out’ of the cells cause the structure and function of the nuclear envelope to be improved. This is a form of cellular rejuvenation, and it has very exciting potential.

“To modify the functional state of an old cell back to a young cell we need to act on the cell biology of ageing itself,” says Larrieu.

“The idea is that rather than tackling age-related conditions one by one, rejuvenating cells back to a younger functional state could delay the appearance of all of these conditions at once.” Delphine Larrieu

She adds: “Until around 15 years ago we always thought that a cell could only go one way, to get older. But a landmark discovery from Nobel Prize winner Shinya Yamanaka showed that it can also go in the reverse direction in a process of cellular reprogramming. This is fascinating.”

Cellular reprogramming has already been shown to work in mice: old mice can be made young again – brimming with health and energy. Excitingly, studies from the Salk Institute showed this also works in progeria mice. But much more work is needed before the technique can be used in humans, because scientists don’t really know what’s happening at the molecular level.

“A full cellular reprogramming in humans could lead to the formation of a lot of cancers, so we need a more subtle approach. We need to make the cells younger, but not take them back so far that they lose their identity,” says Larrieu. “Obviously until we really understand what’s going on we won’t try it in humans.”

Healthier for longer

Happy older woman. Credit: Olesiabilkei/ iStock.

Happy older woman. Credit: Olesiabilkei/ iStock.

As yet, nobody knows whether the healthspan can be increased without also increasing lifespan.

All these Cambridge researchers say that their goal isn’t to find a way to live forever, but to delay the appearance of age-related conditions so people can live healthily for as long as possible.

Unlike our chronological age, which starts ticking at the same rate for everyone from the moment we’re born, our biological age can be completely different – our body might actually be much younger, or older, than we think.

Decades of public health research have shown that to live longer we shouldn’t smoke, shouldn’t drink too much, should eat a healthy diet and exercise regularly. More recently, new techniques show that the right lifestyle choices can actually reverse our biological age. The new medical interventions that may follow from this research could have even stronger anti-ageing effects.

“It’s a really exciting time for ageing research,” says Larrieu. “I think we’re going to start seeing human anti-ageing interventions appearing within the next decade.”

Article published: 20 December 2023

Read more about the University's research on Extending the Healthy Lifespan

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TopBuilt with Shorthand { setTimeout(() => { document.querySelectorAll('#main a').forEach(link => link.classList.remove('campl-external')); }, 2050); }); //--> Summary: 

Research advances at the University of Cambridge mean that the eternal quest to reverse the march of time may soon become a reality

Image: Affiliation (schools and institutions): Department of PharmacologyDepartment of GeneticsSchool of the Biological SciencesPeople (our academics and staff): Delphine LarrieuEwan St. John SmithAlex CaganJanet KumitaSubject (including Spotlight on ... where applicable): ageingStoriesCancerneurodegenerationSection: ResearchNews type: NewsSuper Tags: Health and medicineScienceShorthand Story Description/Subtitle: Research advances at the University of Cambridge mean that the eternal quest to reverse the march of time may soon become a realityShorthand Story Authors: Jacqueline GargetShorthand Story Keywords: influenza, flu, COVID-19, winter, immunity, lockdownShorthand Story Thumbnail: https://www.cam.ac.uk/sites/www.cam.ac.uk/files/shorthand/243861/6DVh94xELz/assets/xxRFivVntY/gettyimages-530313722-v4-skydive-thumbnail.jpg

Clinicians rank patient views as least important in diagnosis, study finds

Mon, 18/12/2023 - 00:16

The research, led by a team at the University of Cambridge and Kings’ College London, found that clinicians ranked patient self-assessments as least important in diagnostic decisions, and said that patients both over- and under-played their symptoms more often than patients reported doing so.

One patient shared the common feeling of being disbelieved as “degrading and dehumanising” and added: “If I had continued to have regard for clinicians’ expertise over mine, I would be dead… When I enter a medical appointment and my body is being treated as if I don’t have any authority over it and what I’m feeling isn’t valid then that is a very unsafe environment… I’ll tell them my symptoms and they’ll tell me that symptom is wrong, or I can’t feel pain there, or in that way.”

In a study published today in Rheumatology, researchers used the example of neuropsychiatric lupus, an incurable autoimmune disease that is particularly challenging to diagnose, to examine the different value given by clinicians to 13 different types of evidence used in diagnoses. This included evidence such as brain scans, patient views, and the observations of family and friends.

Fewer than 4% of clinicians ranked patient’s self-assessments in the top three types of evidence. Clinicians ranked their own assessments highest, despite acknowledging that they often were not confident in diagnoses involving often invisible symptoms, such as headache, hallucinations, and depression. Such ‘neuropsychiatric’ symptoms can lead to low quality of life and earlier death and were reported to be more often misdiagnosed – and therefore not correctly treated – than visible ones such as rashes.

Lead author, Dr Melanie Sloan from the Department of Public Health and Primary Care at the University of Cambridge, said: “It’s incredibly important that we listen to and value patients’ insights and their own interpretations of their symptoms, particularly those with long-standing diseases – after all, they are the people that know what it is like to live with their condition. But we also need to make sure that clinicians have the time to fully explore each patient’s symptoms, something that is challenging within the constraints of current health systems.” 

Almost half (46%) of the 676 patients reported never or rarely having been asked for their self-assessments of their disease, although others discussed very positive experiences. Some clinicians, particularly psychiatrists and nurses, valued patient opinions highly, as a psychiatrist from Wales explained: “Patients often arrive in clinic having had multiple assessments, having researched their own condition to a very high level and having worked hard to understand what is going on with their own body… they are often expert diagnosticians in their own right.”

Patients’ and clinicians’ personal characteristics such as ethnicity and gender were felt to sometimes influence diagnosis, particularly a perception that females are more likely to be told their symptoms are psychosomatic. The data showed that male clinicians were statistically more likely to state that patients over-played symptoms. Patients were more likely than clinicians to say that symptoms were directly caused by the disease.

The study authors acknowledged that patient reasoning will be inaccurate at times, but concluded that there were likely to be many potential benefits (including diagnostic accuracy, fewer misdiagnoses, and greater patient satisfaction) to including patients’ “attributional insights” and experiences into decisions about diagnosis. This is particularly important when diagnostic tests in neuropsychiatric lupus are widely known to be “unenlightening”, according to one neurologist, in common with many other autoimmune diseases and long Covid.

Dr Tom Pollak, senior study author from the Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said: “No human being is always going to be able to accurately pinpoint the cause of symptoms, and patients and clinicians can both get this wrong. But combining and valuing both views, especially when the diagnostic tests aren’t advanced enough to always detect these diseases, may reduce misdiagnoses and improve clinician and patient relationships, which in turn leads to more trust and more openness in symptom reporting.” 

Sue Farrington, Co-Chair of the Rare Autoimmune Rheumatic Disease Alliance, said: “It’s time to move on from the paternalistic, and often dangerous, ‘doctor knows best’ to a more equal relationship where the patients with lived experiences and the doctors with learnt experiences work more collaboratively.” 

The research was funded by The Lupus Trust and LUPUS UK.

Reference
Sloan, M et al. Attribution of neuropsychiatric symptoms and prioritisation of evidence in the diagnosis of neuropsychiatric lupus: mixed methods analysis of patient and clinician perspectives from the international INSPIRE study. Rheumatology; 18 Dec 2023; DOI: 10.1093/rheumatology/kead685

Experts today call for more value to be given to patients’ ‘lived experiences’ as a study of over 1,000 patients and clinicians found multiple examples of patient reports being under-valued.

healthcareMelanie SloanLupus TrustLupus UKSchool of Clinical MedicineDepartment of Public Health and Primary CareIt’s incredibly important that we listen to and value patients’ insights and their own interpretations of their symptoms – after all, they are the people that know what it is like to live with their conditionMelanie SloanNatalia Gdovskaia (Getty Images)Doctor consulting with patient


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