̽��ֱ�� of Cambridge - National Institutes of Health

Scientists identify first genetic marker for MS severity

cjb250 — Wed, 28 Jun 2023 15:00:58 +0000

Multiple sclerosis (MS) is the result of the immune system mistakenly attacking the brain and the spinal cord, resulting in symptom flares known as relapses as well as longer-term degeneration, known as progression. Despite the development of effective treatments for relapses, some of which were pioneered at the ̽��ֱ�� of Cambridge, none can reliably prevent the accumulation of disability.

In findings published today in Nature, an international collaboration of researchers report a genetic variant that increases disease severity, providing the first real progress in understanding and eventually fighting this aspect of MS.

̽��ֱ��work was the result of a large international collaboration of more than 70 institutions from around the world, led by researchers from UCSF (USA) and the ̽��ֱ�� of Cambridge (UK).

“Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” said Professor Sergio Baranzini at UCSF, co-senior author of the study.

“Understanding how the variant exerts its effects on MS severity will hopefully pave the way to a new generation of treatments that are able to prevent disease progression,” said Professor Stephen Sawcer from the ̽��ֱ�� of Cambridge and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, the other co-senior author of the study.

To address the mystery of MS severity, two large MS research consortia joined forces: ̽��ֱ��International Multiple Sclerosis Genetics Consortium (IMSGC) and ̽��ֱ��MultipleMS Consortium. This enabled MS researchers from around the world to pool the resources needed to begin to identify the genetic factors influencing MS outcomes.

Previous studies have shown that MS susceptibility, or risk, stems in large part from dysfunction in the immune system, and some of this dysfunction can be treated, slowing down the disease. But, explained Baranzini, “these risk factors don’t explain why, ten years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons.”

̽��ֱ��two consortia combined data from over 12,000 people with MS to complete a genome-wide association study (GWAS), which uses statistics to carefully link genetic variants to particular traits. In this case, the traits of interest were related to MS severity, including the years it took for each individual to advance from diagnosis to a certain level of disability.

After sifting through more than seven million genetic variants, the scientists found one that was associated with faster disease progression. ̽��ֱ��variant sits between two genes with no prior connection to MS, called DYSF and ZNF638. ̽��ֱ��first is involved in repairing damaged cells, and the second helps to control viral infections. ̽��ֱ��variant’s proximity to these genes suggests that they may be involved in disease progression.

“These genes are normally active within the brain and spinal cord, rather than the immune system,” said Dr Adil Harroud, lead author of the study and former postdoctoral researcher in the Baranzini Lab. “Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.”

̽��ֱ��findings give the field its first leads to address the nervous system component of MS.

̽��ֱ��team also used statistical methods known as 'Mendelian randomisation' to explore the importance of environmental effects and found that years of education and parental age reduced the severity of MS, while smoking worsened it. Finding correlation with these indirect measures of brain health further underlines the importance of resilience in determining the outcome of MS.

“Although it seems obvious that your brain’s resilience to injury would determine the severity of a disease like MS, this new study has pointed us towards the key processes that underlie this resilience,” Sawcer said.

To confirm their findings, the scientists investigated the genetics of nearly 10,000 additional MS patients. Those with two copies of the variant became disabled faster.

Further work will be necessary to determine exactly how this genetic variant affects DYSF, ZNF638, and the nervous system more generally. ̽��ֱ��researchers are also collecting an even larger set of DNA samples from people with MS, expecting to find other variants that contribute to long-term disability in MS.

“This gives us a new opportunity to develop new drugs that may help preserve the health of all who suffer from MS,” said Harroud.

Studying the genetics of multiple sclerosis has been a major theme of neurological research in Cambridge since the late 1980s. With others, members of the Department of Clinical Neurosciences have been closely involved in discovery of the vast majority of gene variants that increase susceptibility.

Professor Alastair Compston from the ̽��ֱ�� of Cambridge and a founding member of the IMSGC added: “Having been personally involved with the identification of susceptibility genes for multiple sclerosis since the 1970s, it is a tribute to those within IMSGC who led this project that fully independent risk variants for progression have now been discovered.

“Once more, the work illustrates the benefits of international collaboration for advancing the understanding of disease mechanisms in multiple sclerosis and other medical conditions”.

This work was supported in part by funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the European Union’s Horizon 2020 Research and Innovation Funding Programme, and the Multiple Sclerosis Society of Canada.

Reference
International Multiple Sclerosis Genetics Consortium and MultipleMS Consortium. Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature; 28 June 2023 DOI: 10.1038/s41586-023-06250-x

A study of more than 22,000 people with multiple sclerosis has discovered the first genetic variant associated with faster disease progression, which can rob patients of their mobility and independence over time.

Although it seems obvious that your brain’s resilience to injury would determine the severity of a disease like MS, this new study has pointed us towards the key processes that underlie this resilience

Stephen Sawcer

eyecrave productions (Getty Images)

Woman with multiple sclerosis

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� 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.

Yes

For the brain, context is key to new theory of movement and memory

Anonymous — Wed, 24 Nov 2021 16:00:00 +0000

How is it that a chef can control their knife to fillet a fish or peel a grape and can wield a cleaver just as efficiently as a paring knife? Even those of us less proficient in the kitchen learn to skilfully handle an astonishing number of different objects throughout our lives, from shoelaces to tennis rackets.

This ability to continuously acquire new skills, without forgetting or degrading old ones, comes naturally to humans but is a major challenge even for today’s most advanced artificial intelligence systems.

Now, scientists from the ̽��ֱ�� of Cambridge and Columbia ̽��ֱ�� (USA) have developed and experimentally verified a new mathematical theory that explains how the human brain achieves this feat. Called the COntextual INference (COIN) model, it suggests that identifying the current context is key to learning how to move our bodies.

̽��ֱ��model describes a mechanism in the brain that is constantly trying to figure out the current context. ̽��ֱ��theory suggests that these continuously changing beliefs about context determine how to use existing memories — and whether to form new ones. ̽��ֱ��results are reported in the journal Nature.

“Imagine playing tennis with a different racket than usual or switching from tennis to squash,” said co-senior author Dr Daniel Wolpert from Columbia ̽��ֱ��. “Our theory explores how your brain adjusts to these situations and whether to treat them as distinct contexts.”

According to the COIN model, the brain maintains a repertoire of motor memories, each associated with the context in which it was created, such as playing squash versus tennis. Even for a single swing of the racket, the brain can draw upon many memories, each in proportion to how much the brain believes it is currently in the context in which that memory was created.

This goes against the traditional view that only one memory is used at a time. To improve performance on the next swing, the brain also updates all memories, once again depending on its belief about the current context. When the context of the movement is judged to be new (the first time we play squash after years of tennis, for example), the brain automatically creates a new memory for that context. This ensures that we do not overwrite previously established memories, such as the memory for playing tennis.

This research may lead to better physical therapy strategies to help people with injuries use their bodies again. Often the improvements seen in the setting of a physical therapist's office do not transfer to improvements in the real world.

“With a better understanding of how context affects motor learning, you can think about how to nudge the brain to generalise what it learns to contexts outside of the physical therapy session,” said first author Dr James Heald. “A better understanding of the basic mechanisms that underlie the context dependence of memory and learning could have therapeutic consequences in this area.”

“What I find exciting is that the principles of the COIN model may also generalise to many other forms of learning and memory, not just memories underlying our movement,” said co-senior author Professor Máté Lengyel from Cambridge’s Department of Engineering. “For example, the spontaneous recurrence of seemingly forgotten memories, often triggered by a change in our surroundings, has been observed both in motor learning and in post-traumatic stress disorder.”

COINing a new model

Practice with a tennis racket, and the brain forms motor memories of how you moved your arm and the rest of your body that improve your serve over time. But learning isn’t as simple as just making better memories to make movements more precise, the researchers said. Otherwise, a tennis player’s serves might improve to the point at which they never hit a ball out of bounds. ̽��ֱ��real world and our nervous systems are complex, and the brain has to deal with a lot of variability.

How does the brain distinguish this noise — these random fluctuations — from new situations? And how does it understand that a slightly lighter tennis racket can still be operated using previous tennis racket memories? But that a table tennis paddle is an entirely different kind of object that requires starting from scratch?

̽��ֱ��answer, according to the COIN model, may be Bayesian inference, a mathematical technique used to deal with uncertainty. This method statistically weighs new evidence in light of prior experience in order to update one's beliefs in a changeable world. In the COIN model, a context is a simplifying assumption that, in a given set of circumstances, certain actions are more likely to lead to some consequences than others. ̽��ֱ��new theory's acceptance of the role that uncertainty plays in motor learning is similar to how quantum physics views the universe in terms of probabilities instead of certainties, the scientists noted.

Getting a handle on the theory

̽��ֱ��researchers put the COIN model to the test on data from previous experiments, as well as new experiments, in which volunteers interacted with a robotic handle. Participants learned to manipulate the handle to reach a target while the handle pushed back in different ways.

Volunteers who spent time learning to operate the handle as it pushed to the left, for instance, had more trouble operating the handle when it changed behaviour and pushed to the right, as compared to volunteers who started with a handle pushing to the right. ̽��ֱ��COIN model explained this effect, called anterograde interference.

“ ̽��ֱ��longer you learn one task, the less likely you are to move into a new context with the second task,” said Wolpert. “You’re still forming a motor memory of the second task, but you’re not using it yet because your brain is still stuck back in the first context.”

̽��ֱ��model also predicted that a learned skill can re-emerge even after subsequent training seems to have erased it. Called spontaneous recovery, this re-emergence is seen in many other forms of learning besides motor learning. For example, spontaneous recovery has been linked with challenges in treating post-traumatic stress disorder, where contexts can trigger traumatic memories to spontaneously recur.

Scientists usually explain spontaneous recovery by invoking two different learning mechanisms. In one, memories learned quickly are forgotten quickly, and in the other, memories learned slowly are forgotten slowly, and can thus reappear. In contrast, the COIN model suggests there is just one mechanism for learning instead of two separate ones, and that memories that apparently vanished may be ready to pop back with the right trigger: the belief that the context has re-emerged. ̽��ֱ��researchers confirmed this in their lab with new experiments.

Máté Lengyel is a Fellow of Churchill College. ̽��ֱ��research was supported by the European Research Council, the Wellcome Trust, the Royal Society, the National Institutes of Health, and the Engineering and Physical Sciences Research Council.

Reference:
James B Heald, Máté Lengyel and Daniel M Wolpert. ‘Contextual inference underlies the learning of sensorimotor repertoires.’ Nature (2021). DOI: 10.1038/s41586-021-04129-3

Adapted from a Columbia ̽��ֱ�� press release.

Mathematical model could help in physical therapy and shed light on learning more generally.

̽��ֱ��COIN model may also generalise to many other forms of learning and memory, not just memories underlying our movement

Máté Lengyel

Chino Rocha via Unsplash

Tennis match

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� 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.

Yes

Stress does not lead to loss of self-control in eating disorders, study finds

cjb250 — Mon, 12 Apr 2021 17:00:58 +0000

People who experience bulimia nervosa and a subset of those affected by anorexia nervosa share certain key symptoms, namely recurrent binge-eating and compensatory behaviours, such as vomiting. ̽��ֱ��two disorders are largely differentiated by body mass index (BMI): adults affected by anorexia nervosa tend to have BMI of less than 18.5 kg/m2. More than 1.6 million people in the UK are thought to have an eating disorder, three-quarters of whom are women.

One prominent theory of binge-eating is that it is a result of stress, which causes individuals to experience difficulties with self-control. However, until now, this theory has not been directly tested in patients.

To examine this theory, researchers at the ̽��ֱ�� of Cambridge, working with clinicians at Cambridgeshire and Peterborough NHS Foundation Trust, invited 85 women – 22 with anorexia nervosa, 33 with bulimia nervosa and 30 healthy controls – to attend a two-day stay at Wellcome-MRC Institute of Metabolic Science Translational Research Facility (TRF). ̽��ֱ��facility, which includes an Eating Behaviour Unit, is designed so that a volunteer’s diet and environment can be strictly controlled and their metabolic status studied in detail during a residential status. ̽��ֱ��setting is intended to be as naturalistic as possible.

During their stay, each morning the women would receive controlled meals provided by a nutritionist. ̽��ֱ��women then underwent a fasting period during which they were taken to the next door Wolfson Brain Imaging Centre, where they performed tasks while their brain activity was monitored using a functional MRI scanner.

̽��ֱ��first tasks involved stopping the progression of a bar rising up a computer screen by pressing a key. ̽��ֱ��main task involved stopping the moving bar as it reached the middle line. On a minority of trials, stop-signals were presented, where the moving bar stopped automatically before reaching the middle line; participants were instructed to withhold their response in the event of a stop-signal.

̽��ֱ��women then performed a task aimed at raising their stress levels. They were asked to carry out a series of mental arithmetic tests while receiving mild but unpredictable electric shocks, and were told that if they failed to meet the performance criterion, their data would be dismissed from the study. They were given feedback throughout the task, such as ‘Your performance is below average’.

̽��ֱ��women then repeated the stop-signal task again.

Once the tasks had been completed – but while the volunteers might still be expected to be in a heightened state of stress – they returned to the Eating Behaviour Unit, where they were offered an ‘all you can eat’ buffet in its relaxing lounge and were told they could eat as much or as little as they would like.

On the second day of their study, the volunteers carried out the same tasks, but without the added stress of unpleasant electric shocks and pressure to perform. (For some participants, the order of the days was reversed.)

Dr Margaret Westwater, who led the research while a PhD student at Cambridge’s Department of Psychiatry, said: “ ̽��ֱ��idea was to see what happened when these women were stressed. Did it affect key regions of the brain important for self-control, and did that in turn lead to increases in food intake? What we found surprised us and goes counter to the prevailing theory.”

̽��ֱ��team found that even when they were not stressed, those women with bulimia nervosa performed worse on the main task, where they had to stop the rising bar as it reached the middle bar - but this was not the case for those women affected by anorexia nervosa. This impairment occurred alongside increased activity in a region in the prefrontal cortex, which the team say could mean these particular women were unable to recruit some other regions required by the brain to perform the task optimally.

Interestingly – and contrary to the theory – stress did not affect the actual performance in any way for either of the patient groups or the controls. However, the patient groups showed some differences in brain activity when they were stressed – and this activity differed between women with anorexia and those with bulimia.

While the researchers observed that the patients in general ate less in the buffet than the controls, the amount that they ate did not differ between the stress and control days. However, activity levels in two key brain regions were associated with the amount of calories consumed in all three groups, suggesting that these regions are important for dietary control.

Dr Westwater added: “Even though these two eating disorders are similar in many respects, there are clear differences at the level of the brain. In particular, women with bulimia seem to have a problem with pre-emptively slowing down in response to changes in their environment, which we think might lead them to make hasty decisions, leaving them vulnerable to binge-eating in some way.

“ ̽��ֱ��theory suggests that these women should have eaten more when they were stressed, but that's actually not what we found. Clearly, when we're thinking about eating behaviour in these disorders, we need to take a more nuanced approach.”

In findings published last year, the team took blood samples from the women as they performed their tasks, to look at metabolic markers that are important for our sense of feeling hungry or feeling full. They found that levels of these hormones are affected by stress.

Under stress, patients with anorexia nervosa had an increase in ghrelin, a hormone that tells us when we are hungry. But they also had an increase in peptide tyrosine tyrosine (PYY), a satiety hormone. In other words, when they are stressed, people with anorexia nervosa produce more of the hunger hormone, but contradictorily also more of a hormone that should tell them that they are full, so their bodies are sending them confusing signals about what to do around food.

̽��ֱ��situation with bulimia nervosa was again different: while the team saw no differences in levels of ghrelin or PYY, they did see lower levels of cortisol, the ‘stress hormone’, than in healthy volunteers. In times of acute stress, people who are chronically stressed or are experiencing depression are known to show this paradoxical low cortisol phenomenon.

Professor Paul Fletcher, joint senior author at the Department of Psychiatry, said: “It’s clear from our work that the relationship between stress and binge-eating is very complicated. It’s about the environment around us, our psychological state and how our body signals to us that we’re hungry or full.

“If we can get a better understanding of the mechanisms behind how our gut shapes those higher order cognitive processes related to self-control or decision-making, we may be in a better position to help people affected by these extremely debilitating illnesses. To do this, we need to take a much more integrated approach to studying these illnesses. That's where facilities such as Cambridge’s new Translational Research Facility can play a vital role, allowing us to monitor within a relatively naturalistic environment factors such as an individual’s behaviour, hormone levels and, brain activity.”

̽��ֱ��research was funded by the Bernard Wolfe Health Neuroscience Fund, Wellcome, the NIH-Oxford-Cambridge Scholars Program and the Cambridge Trust. Further support was provided by the NIHR Cambridge Biomedical Research Centre.

Reference
Westwater, ML, et al. Prefrontal responses during proactive and reactive inhibition are differentially impacted by stress in anorexia and bulimia nervosa. JNeuro; 12 April 2021; DOI: 10.1523/JNEUROSCI.2853-20.2021

A unique residential study has concluded that, contrary to perceived wisdom, people with eating disorders do not lose self-control – leading to binge-eating – in response to stress. ̽��ֱ��findings of the Cambridge-led research are published today in the Journal of Neuroscience.

It’s clear from our work that the relationship between stress and binge-eating is very complicated. It’s about the environment around us, our psychological state and how our body signals to us that we’re hungry or full

Paul Fletcher

Volkan Olmez

Grey-scale image of a woman

Yes

Licence type:

Public Domain

Scientists identify warning signs over effectiveness of HIV ‘wonder drug’ in sub-Saharan Africa

cjb250 — Tue, 01 Dec 2020 10:00:00 +0000

As HIV copies itself and replicates, it can develop errors, or ‘mutations’, in its genetic code (its RNA). While a drug may initially be able to suppress or even kill the virus, certain mutations can allow the virus to develop resistance to its effects. If a mutated strain begins to spread within a population, it can mean once-effective drugs are no longer able to treat people.

HIV treatment usually consists of a cocktail of drugs that includes a type of drug known as a non-nucleoside reverse-transcriptase inhibitor (NNRTI). However, in recent years, HIV has begun to develop resistance to NNRTIs. Between 10% and 15% of patients in much of sub-Saharan Africa are infected by a strain of HIV resistant to these drugs. If a patient is infected with an NNRTI-resistant strain, they are at a two- to three-fold increased risk of the drug regimen failing.

In 2019, the World Health Organization began to recommend dolutegravir as the preferred first-line treatment for HIV in most populations. Dolutegravir was dubbed a ‘wonder drug’ because it was safe, potent and cost-effective and scientists had seen no drug resistance against it in clinical trials. However, there is little data on the success of dolutegravir against circulating strains of HIV in sub-Saharan Africa.

In a study published today in Nature Communications, an international team of researchers from South Africa, the UK and the USA examined the genetic code of HIV to determine if drug resistance mutations in 874 volunteers living with HIV affected their treatment success. ̽��ֱ��individuals were enrolled in a clinical trial for people initiating HIV treatment to compare two drug regimens: efavirenz, an NNRTI and prior first-line therapy in the region, and dolutegravir.

̽��ֱ��goal of this study was to determine whether drug resistance to efavirenz prior to starting treatment affected treatment success (suppression of the virus in the blood) over the first two years of therapy with both of these two regimens.

As expected, the presence of drug resistance substantially reduced the chances of treatment success in people taking efavirenz, successfully suppressing the virus over 96 weeks in 65% of participants, compared to 85% of non-resistant individuals. However, unexpectedly, the same pattern was true for individuals taking dolutegravir-based treatments: 66% of those with efavirenz resistance mutations remained suppressed over 96 weeks, compared to 84% of those without the mutations. These relationships held true after accounting for other factors, such as treatment adherence.

“We fully expected efavirenz to be less effective among patients HIV strains resistant to NNRTIs,” said Dr Mark Siedner, faculty member at the Africa Health Research Institute in KwaZulu-Natal, South Africa and Massachusetts General Hospital in Boston, Massachusetts. “What took us completely by surprise was that dolutegravir – a different class of drug which is generally effective in the face of drug resistance – would also be less effective in people with these resistant strains.

“We are working now to tease out if this was due to the virus or the participants – for instance, if people with resistance are less likely to take their pills regularly. Either way, if this pattern holds true, it could have far reaching impacts on our predictions of long-term treatment control for millions of people taking dolutegravir in the region.”

Professor Ravi Gupta from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “This a huge concern. Dolutegravir was very much seen as a ‘wonder drug’, but our study suggests it might not be as effective in a significant number of patients who are resistant to another important class of antiretroviral drugs.”

̽��ֱ��researchers say it is not clear why efavirenz-resistant mutations should affect susceptibility of dolutegravir, though one hypothesis is that integrase inhibitors such as dolutegravir push the virus to replicate and mutate faster, in turn developing resistance to the new drug in an evolutionary arms race. Alternatively, it could be due to poor adherence to treatment regimens, even though the analysis accounted for adherence by two independent methods. Further research is needed to find out why.

Professor Gupta added: “What this shows is that we urgently need to prioritise point of care tests to identify people with drug resistance HIV, particularly against efavirenz, and to more closely and accurately monitor treatment adherence. ̽��ֱ��development of such tests is at an advanced stage, but there a lack of investment from funders and philanthropic donors. We urgently need agencies and individuals to step forward and help support these programmes.

“In addition, we need to provide widespread access to viral load monitoring so that we can find those who are struggling, get them on more appropriate regimens, and limit the emergence of resistance when patients are failing therapy.”

̽��ֱ��study was carried out by researchers at: the Africa Health Research Institute, ̽��ֱ�� of KwaZulu-Natal, ̽��ֱ�� of Witwatersrand, KwaZulu-Natal Research Innovation and Sequencing Platform, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA), in South Africa; the ̽��ֱ�� of Cambridge, ̽��ֱ�� of Liverpool, and Imperial College London in the UK; and Massachusetts General Hospital and Harvard Medical School, USA.

̽��ֱ��research was supported by USAID, Unitaid, the South African Medical Research Council (SAMRC), with investigational drug donated by ViiV Healthcare and Gilead Sciences, and by Wellcome and the National Institutes of Health.

Reference
Siedner, MJ et al. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nat Comms; 1 Dec 2020; DOI: 10.1038/s41467-020-19801-x

Dolutegravir, the current first-line treatment for HIV, may not be as effective as hoped in sub-Saharan Africa, suggests new research published on World AIDS Day. ̽��ֱ��study finds that this so-called ‘wonder drug’ may be less effective in patients resistant to older drugs.

Dolutegravir was very much seen as a ‘wonder drug’, but our study suggests it might not be as effective in a significant number of patients who are resistant to another important class of antiretroviral drugs

Ravi Gupta

Jon Rawlinson

Know your HIV status sign in Africa

Yes

Licence type:

Attribution-ShareAlike

World’s first artificial pancreas app licensed for people with type 1 diabetes in UK

cjb250 — Mon, 16 Mar 2020 00:39:50 +0000

̽��ֱ��CamAPS FX app works with an insulin pump and a glucose monitor to automatically deliver insulin to people living with the condition via a complex algorithm.

Around 400,000 people in the UK are affected by type 1 diabetes, 29,000 of them children. It is a chronic, life-threatening condition that has a life-long impact on those diagnosed with it and their families. Currently, people with type 1 diabetes rely on a routine of finger-prick blood tests and insulin injections or infusions just to stay alive, because their pancreas no longer produces insulin itself.

̽��ֱ��app - which Professor Hovorka hopes will become available on the NHS in the future - will take over much of the management of the condition. This is particularly important at night, when many people with type 1 diabetes experience potentially dangerous low blood glucose levels.

̽��ֱ��app can also upload the user’s blood glucose measurements seamlessly to Diasend, an online platform, allowing their diabetes team to provide more personalised care.

̽��ֱ��CamAPS FX app is backed by 13 years of clinical research carried out by Professor Hovorka and his research group at the Wellcome-MRC Institute of Metabolic Science. It is licensed for use by both adults and children with the condition and is the first artificial pancreas system to be licensed for use in pregnancy, or by young children aged one and above.

Professor Hovorka said: “This is a major stepping stone towards providing widely available, clinically proven, and user-friendly artificial pancreas technology to people with type 1 diabetes.

“Our aim is to alleviate the ever-present burden of type 1 diabetes and improve health outcomes. This is the outcome of hard work, with more to come. We are indebted to all who are helping us on this journey.”

At launch, the app will be supported by a small number of UK diabetes clinics. People who wish to use the app will need to confirm which clinic they attend, and must be using a Dana RS pump and a Dexcom G6 continuous glucose monitor.

Professor Hovorka and his research team will work to continue to bring this technology to all who need it, via the NHS. Key to this will be the generation of data to support the case for NHS provision.

̽��ֱ��commercial launch is a milestone in the journey towards a fully automated artificial pancreas for everyone with type 1 diabetes. Such technology will fundamentally change life with the condition by working with a range of insulin pumps and glucose monitors to lift the burden of managing a condition that is relentlessly unpredictable day and night.

Professor Hovorka will continue refining the artificial pancreas through research into mealtime glucose control and improving ease of use.

̽��ֱ��research behind the app has been funded by the type 1 diabetes charity JDRF, Diabetes UK, the National Institute for Health Research, the National Institutes of Health, Horizon 2020, and the Leona M and Harry B Helmsley Charitable Trust.

Karen Addington, UK Chief Executive of JDRF, said: “JDRF is proud to have supported Professor Hovorka’s artificial pancreas research from the beginning, nearly 15 years ago. This app is a major innovation and a significant milestone on the road to a fully automated and interoperable artificial pancreas. There’s still more work to do, but this is an exciting step.”

Fiona O’Reilly, who has been using the app as part of a clinical trial, said: “Overall, it makes me feel free. It is the closest I have been to living without the burden of type 1 diabetes since I was diagnosed, which is a fabulous feeling – I feel less fearful of hypoglycaemia, and less ashamed of the fact that I find achieving good glycaemic control so tricky.

“And it makes me feel more positive of my future with diabetes, that I have a chance of avoiding all the associated complications. It also makes me feel lucky to live in a time where this technology is possible and really grateful to be given the chance to try it out.”

̽��ֱ��app is now available for UK users to download onto Android phones via the Amazon Appstore. ̽��ֱ��app is available on a subscription basis starting at £70 per month.

Adapted from a press release by the JDRF.

̽��ֱ��world’s first licensed, downloadable artificial pancreas app for people with type 1 diabetes launches today, based on over a decade of research by Professor Roman Hovorka at the ̽��ֱ�� of Cambridge and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust.

This is a major stepping stone towards providing widely available, clinically proven, and user friendly artificial pancreas technology to people with type 1 diabetes

Roman Hovorka

Screenshot from CamAPS FX app

Yes

Pregnancy losses and large numbers of children linked with increased risk of cardiovascular disease

cjb250 — Fri, 30 Nov 2018 00:36:32 +0000

Women who experience pregnancy loss and do not go on to have children are at greater risk of cardiovascular disease, such as heart disease and stroke, compared with women who have only one or two children, according to new research from the ̽��ֱ�� of Cambridge and the ̽��ֱ�� of North Carolina.

̽��ֱ��study, published today in the Journal of Women’s Health, also found that women who have five or more children are at an increased risk of cardiovascular disease in later life.

Cardiovascular disease is the leading cause of death among women in every major developed country and most emerging economies. Approximately 28,000 women die from heart attacks each year in the UK. In 2016 alone, 20,000 women died after having a stroke – a higher number that that in men.

During pregnancy, the mother’s body experiences changes during pregnancy including weight gain and accumulation of abdominal fat, higher levels of cholesterol, increased insulin resistance, and changes in the structure of the heart. Although most changes that occur during pregnancy are temporary, these changes are known to be risk factors for cardiovascular disease in the general population.

Previous studies have attempted to assess the relationship between pregnancy and childbirth on the one hand and cardiovascular disease on the other. However, due to limitations in these studies – including not taking into account breastfeeding history and grouping together women who had never been pregnant with those who had been pregnant but experienced pregnancy loss – their results have been inconclusive and sometimes contradictory.

In this new study, a team of researchers in the US and the UK analysed data from more than 8,500 White and African-American women, aged 45-64 years, in the US. This included health service data on cardiovascular disease over a thirty year period (1987-2016) and self-reported data on the number of pregnancies and births, and breastfeeding practices.

Within the study population, 138 women reported having experienced pregnancy loss and having no live born children. 3,108 women had one or two live born children, 3,126 had 3-4 live born children, and 1,694 had five or more live born children.

̽��ֱ��researchers found that women who experienced pregnancy loss and did not have any live born children were at 64% greater risk of both coronary heart disease and 46% greater risk of heart failure compared to women with one or two children. Women with five or more births had a 38% higher risk of having serious heart attack, regardless of how long they breastfed for.

̽��ֱ��team say that there may be several possible reasons for the link between cardiovascular risk and multiple births. Repeated pregnancies could result in long-lasting changes within the body including weight gain, especially around the waist, and increased levels of cholesterol in the blood. Also, the number of children a woman has also encompasses other factors including child-rearing, age at menopause and health conditions. Therefore, the researchers say it is unclear whether the increased risk of heart failure, coronary heart disease and heart attacks reflect the direct impact of repeated pregnancies, or the stressors associated with rearing multiple children, or both.

̽��ֱ��increased risk of coronary heart disease and heart failure found in women with prior pregnancies, but no live born children, may reflect the increased risk previously identified after a history of miscarriage. Several mechanisms have been proposed to underlie the relationship between miscarriage and coronary heart disease, including immune disorders, chronic disease and dysfunction of the endothelium (cells that line the interior of blood vessels).

“Conditions such as heart disease and stroke together are the leading cause of death in women in the developed world and it is essential that we understand why this is the case,” says Dr Clare Oliver-Williams, a Junior Research Fellow at Homerton College who works at from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge. “Our work suggests that there is a relation between cardiovascular disease risk and both pregnancy loss and having a large number of births.

“This study isn’t designed to stress and worry women, especially those who have experienced the distress of pregnancy loss. Instead we want to empower women with knowledge that will help them to reduce their risk.

“Most women know by the age of 40 how many children and pregnancy losses they have had, which is years before most heart attacks and strokes occur. This provides a window of opportunity to make lifestyle changes, such as exercise and diet that can help reduce the risk of cardiovascular disease.”

̽��ֱ��research was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, in the USA, and the British Heart Foundation and Homerton College, ̽��ֱ�� of Cambridge, in the UK.

Reference
Oliver-Williams, C, et al. ̽��ֱ��association between parity and subsequent cardiovascular disease in women: ̽��ֱ��Atherosclerosis Risk in Communities (ARIC) Study. ̽��ֱ��Journal of Women’s Health; 27 Nov 2018; DOI: 10.1089/jwh.2018.7161

Conditions such as heart disease and stroke together are the leading cause of death in women in the developed world and it is essential that we understand why this is the case

Clare Oliver-Williams

Geralt

Heart

Researcher profile: Dr Clare Oliver-Williams

Dr Clare Oliver-Williams first came to Cambridge in 2002 to study Natural Science as an undergraduate “and never fully left”, as she puts it. She studied her PhD here and is now a Junior Research Fellow at Homerton College.

Clare took a career break to have a family, but says she received “excellent support that made returning to academia feasible and enjoyable”. Her time now tends to be spent between her college or the Department of Public Health and Primary Care, though her research involves collaborating with researchers across the world, including in the United States and Europe, which has given her the opportunity to travel widely including to Denmark and North Carolina.

“Cambridge is a wonderful place to work for so many reasons,” she says. “It’s a hub of knowledge and activity, bringing together people from around the world. ̽��ֱ��enthusiasm so many researchers have for their work is infectious. It can make for inspiring conversations where you hear about the work and passions of others. Even when the topic of conversation is far removed from your own interests, you walk away feeling energised and motivated.”

Clare’s own research builds on her PhD, which focused on the link between miscarriages and the development of heart disease in women. She is now trying to understand the relationship between a range of female traits, such as the menopause and pregnancy, and the risk of cardiovascular disease.

“Cardiovascular disease is often thought of as a primarily male disease, but it affects large numbers of women as well,” she says. “Women undergo unique experiences in their reproductive life which may affect their risk of cardiovascular disease. I want to further our understanding of what these experiences are, and what they mean for the long-term health of women.”

Clare says she has already had her own, “tiny 15 minutes of fame” when at a British Cardiovascular Society conference, where her work led to a surprising amount of media attention, including being interviewed on live radio, being recorded for a podcast and responding to lots of email queries. It also helped her get noticed by her fellow conference attendees.

“To top it all off, I ended up winning a prize at the hackathon, an event devoted to developing solutions to clinical problems. As the announcement of the winners was late, my team mate and I ended up with my children alongside us when we accepted the award on stage!”

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