World first for AI and machine learning to treat COVID-19 patients worldwide
The research was sparked by the pandemic and set out to build an AI tool to predict how much extra oxygen a Covid-19 patient may need in the first days of hospital care, using data from across four continents.
The technique, known as federated learning, used an algorithm to analyse chest x-rays and electronic health data from hospital patients with Covid symptoms.
To maintain strict patient confidentiality, the patient data was fully anonymised and an algorithm was sent to each hospital so no data was shared or left its location.
Once the algorithm had ‘learned’ from the data, the analysis was brought together to build an AI tool which could predict the oxygen needs of hospital Covid patients anywhere in the world.
Published today in Nature Medicine, the study dubbed EXAM (for EMR CXR AI Model), is one of the largest, most diverse clinical federated learning studies to date.
To check the accuracy of EXAM, it was tested out in a number of hospitals across five continents, including Addenbrooke’s Hospital. The results showed it predicted the oxygen needed within 24 hours of a patient’s arrival in the emergency department, with a sensitivity of 95 per cent and a specificity of over 88 per cent.
“Federated learning has transformative power to bring AI innovation to the clinical workflow,” said Professor Fiona Gilbert, who led the study in Cambridge and is honorary consultant radiologist at Addenbrooke’s Hospital and chair of radiology at the University of Cambridge School of Clinical Medicine.
“Our continued work with EXAM demonstrates that these kinds of global collaborations are repeatable and more efficient, so that we can meet clinicians’ needs to tackle complex health challenges and future epidemics.”
First author on the study, Dr Ittai Dayan, from Mass General Bingham in the US, where the EXAM algorithm was developed, said:
“Usually in AI development, when you create an algorithm on one hospital’s data, it doesn’t work well at any other hospital. By developing the EXAM model using federated learning and objective, multimodal data from different continents, we were able to build a generalizable model that can help frontline physicians worldwide.”
Bringing together collaborators across North and South America, Europe and Asia, the EXAM study took just two weeks of AI ‘learning’ to achieve high-quality predictions.
“Federated Learning allowed researchers to collaborate and set a new standard for what we can do globally, using the power of AI,'' said Dr Mona G Flores, Global Head for Medical AI at NVIDIA. “This will advance AI not just for healthcare but across all industries looking to build robust models without sacrificing privacy.”
The outcomes of around 10,000 COVID patients from across the world were analysed in the study, including 250 who came to Addenbrooke’s Hospital in the first wave of the pandemic in March/April 2020.
The research was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC).
Work on the EXAM model has continued. Mass General Brigham and the NIHR Cambridge BRC are working with NVIDIA Inception startup Rhino Health, cofounded by Dr Dayan, to run prospective studies using EXAM.
Professor Gilbert added: “Creating software to match the performance of our best radiologists is complex, but a truly transformative aspiration. The more we can securely integrate data from different sources using federated learning and collaboration, and have the space needed to innovate, the faster academics can make those transformative goals a reality.”
Reference
Dayan, I et al. Federated learning for predicting clinical outcomes in patients with COVID-19. Nat Med; 15 Sept 2021; DOI: 10.1038/s41591-021-01506-3
Addenbrooke’s Hospital in Cambridge along with 20 other hospitals from across the world and healthcare technology leader, NVIDIA, have used artificial intelligence (AI) to predict Covid patients’ oxygen needs on a global scale.
COVID-19CoronavirusArtificial intelligenceFiona GilbertNIHR Cambridge Biomedical Research CentreSchool of Clinical MedicineDepartment of RadiologyAddenbrooke's HospitalCambridge University Hospitals NHS Foundation TrustCreating software to match the performance of our best radiologists is complex, but a truly transformative aspirationFiona GilbertMehrnews.comA clinician helping a COVID-19 patient with an oxygen mask in a hospital in Iran
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Changes to workplace cafeteria menus nudge workers to consume fewer calories
Researchers at the University of Cambridge, who led the study, say that even simple interventions such as these could contribute towards tackling levels of obesity.
Unhealthy eating, including eating more calories than are needed, plays a major role in the increasing rates of obesity. This in turn increases the risk of diseases such as type 2 diabetes, heart disease and many cancers, contributing to increasing rates of premature death worldwide.
The environments in which we live and work influence the types of food and drink that we consume. Local areas of deprivation in particular magnify this effect – people living in less affluent areas or with lower socioeconomic status tend to have reduced access to healthy foods and higher rates of obesity.
One important environment where interventions could be implemented is cafeterias, such as those in schools, universities, and workplaces. The workplace is the most common place to eat outside of the home, typically 15% of working adults’ energy intake.
In the largest study of its kind, a team from the University of Cambridge tested the impact on calories purchased of changing both portion sizes and availability of some higher calorie food and drink in 19 workplace cafeterias over a six month period. The results of their study are published today in PLOS Medicine.
The team recruited workplace cafeterias based in the distribution centres of a major UK supermarket chain.
Over a 25-week-long period, the team, working with the caterers, replaced some higher calorie food and drink products with lower calorie ones – for example, swapping bacon and cheese burgers with grilled chicken burgers. This led to a 4.8% reduction in the average number of calories purchased a day.
Next, as well as reducing the availability of high calorie food and drink products, the team reduced the portion size of some higher calorie products by about 14% in volume – for example by serving a smaller slice of lasagne or portion of chips or reducing the number of meatballs in a portion.
When both the availability and size of high calorie food and drink portions were changed, this led to an 11.5% reduction in the average number of calories purchased per day compared to the baseline. For the typical worker, this would be equal to eating about 50kcal fewer per day.
Dr James Reynolds from the Behaviour and Health Research Unit at the University of Cambridge, the study’s first author, said: “On average, UK adults consume 200-300 excess calories a day. This study shows that reducing portion sizes and the availability of higher calorie options in cafeterias could make an important contribution to reducing excess calories in strategies to tackle obesity.
“If cafeterias in workplaces, schools, and universities implemented these changes, this could help reduce overconsumption of calories and help in widespread efforts to reduce population-level obesity.”
The workplaces where the cafeterias were located were predominantly staffed by those working in manual occupations, who have – on average – worse health outcomes and higher body mass indexes (BMIs) compared to those in non-manual occupations.
Senior author Professor Dame Theresa Marteau, Director of the Behaviour and Health Research Unit, added: “Many of the measures introduced to reduce calorie consumption, such as mass media campaigns, have little overall impact, but can exacerbate health inequalities, helping mainly those who work in non-manual jobs. We need to find interventions that works across the board. Our study suggests that making relatively simple changes to menus in workplace and other cafeterias could make an important contribution to tackling obesity in all groups.”
The study took place over a longer time period and used more sites than previous studies. Sustained behaviour change is known to be a major obstacle to reducing body mass index (BMI), but the researchers found no evidence that the effect of the intervention diminished with time during their study.
The cafeterias experienced a small drop in the amount of money taken at the till – 2.6% when just the availability of options was reduced and a 5.7% drop when the portion sizes were also decreased. The researchers suggest this may have been a temporary effect, as the drop decreased over time, and may in part be due to the fixed menu and product list that was required for the study.
Dr Reynolds added: “Cafeterias should be able to compensate for a small drop in revenue by changing which products they sell or by additional strategies to make healthier food options more appealing.”
The study was funded by Wellcome Trust and Cancer Research UK.
Reference
Reynolds, JP et al. Impact of decreasing the proportion of higher energy foods and reducing portion sizes on food purchased in worksite cafeterias: a stepped-wedge randomised controlled trial. PLOS Medicine; 14 Sept 2021; DOI: 10.1371/journal.pmed.1003743
A study carried out at 19 workplace cafeterias has shown that reducing portion sizes and replacing higher calorie food and drinks with lower calorie options led to workers buying food and drink with fewer calories.
Public healthhealthObesityTheresa MarteauJames ReynoldsWellcomeCancer Research UK (CRUK)School of Clinical MedicineCambridge Public HealthBehaviour and Health Research Unit (BHRU)Our study suggests that making relatively simple changes to menus in workplace and other cafeterias could make an important contribution to tackling obesityTheresa Marteau
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Four Cambridge researchers recognised in the 2022 Breakthrough Prizes
Professors Shankar Balasubramanian and David Klenerman, from Cambridge’s Yusuf Hamied Department of Chemistry, have been awarded the 2022 Breakthrough Prize in Life Sciences – the world’s largest science prize – for the development of next-generation DNA sequencing. They share the award with Pascal Mayer, from the French company Alphanosos.
In addition, Professor Suchitra Sebastian, from the Cavendish Laboratory, and Professor Jack Thorne, from the Department of Pure Mathematics and Mathematical Statistics, have been recognised with the New Horizons Prize, awarded to outstanding early-career researchers.
Professor Suchitra Sebastian has been awarded the 2022 New Horizons in Physics Prize for high precision electronic and magnetic measurements that have profoundly changed our understanding of high temperature superconductors and unconventional insulators.
Professor Jack Thorne has been awarded the 2022 New Horizons in Mathematics Prize, for transformative contributions to diverse areas of algebraic number theory, and in particular for the proof, in collaboration with James Newton, of the automorphy of all symmetric powers of a holomorphic modular newform.
Professors Balasubramanian and Klenerman co-invented Solexa-Illumina Next Generation DNA Sequencing (NGS), technology that has enhanced our basic understanding of life, converting biosciences into ‘big science’ by enabling fast, accurate, low-cost and large-scale genome sequencing – the process of determining the complete DNA sequence of an organism’s make-up. They co-founded the company Solexa to make the technology available to the world.
The benefits to society of rapid genome sequencing are huge. The almost immediate identification and characterisation of the virus which causes COVID-19, rapid development of vaccines, and real-time monitoring of new genetic variants would have been impossible without the technique Balasubramanian and Klenerman developed.
The technology has had – and continues to have – a transformative impact in the fields of genomics, medicine and biology. One measure of the scale of change is that it has allowed a million-fold improvement in speed and cost when compared to the first sequencing of the human genome. In 2000, sequencing of one human genome took over 10 years and cost more than a billion dollars: today, the human genome can be sequenced in a single day at a cost of less than $1,000. More than a million human genomes are sequenced at scale each year, thanks to the technology co-invented by Professors Balasubramanian and Klenerman, meaning we can understand diseases much better and much more quickly. Earlier this year, they were awarded the Millennium Technology Prize. Balasubramanian is also based at the Cancer Research UK Cambridge Institute, and is a Fellow of Trinity College. Klenerman is a Fellow of Christ's College.
Professor Sebastian’s research seeks to discover exotic quantum phases of matter in complex materials. Her group’s experiments involve tuning the co-operative behaviour of electrons within these materials by subjecting them to extreme conditions including low temperature, high applied pressure, and intense magnetic field.
Under these conditions, her group can take materials that are quite close to behaving like a superconductor – perfect, lossless conductors of electricity – and ‘nudge’ them, transforming their behaviour.
“I like to call it quantum alchemy – like turning soot into gold,” Sebastian said. “You can start with a material that doesn’t even conduct electricity, squeeze it under pressure, and discover that it transforms into a superconductor. Going forward, we may also discover new quantum phases of matter that we haven’t even imagined.”
In addition to her physics research, Sebastian is also involved in theatre and the arts. She is Director of the Cavendish Arts-Science Project, which she founded in 2016. The programme has been conceived to question and explore material and immaterial universes through a dialogue between the arts and sciences.
“Being awarded the New Horizons Prize is incredibly encouraging, uplifting and joyous,” said Sebastian. “It recognises a discovery made by our team of electrons doing what they're not supposed to do. It's gone from the moment of elation and disbelief at the discovery, and then trying to follow it through, when no one else quite thinks it’s possible or that it could be happening. It’s been an incredible journey, and having it recognised in this way is incredibly rewarding.”
Professor Jack Thorne is a number theorist in the Department of Pure Mathematics and Mathematical Statistics. One of the most significant open problems in mathematics is the Riemann Hypothesis, which concerns Riemann’s zeta function. Today we know that the zeta function is intimately tied up with questions concerning the statistical distribution of prime numbers, such as how many prime numbers there are, how closely they can be found on the number line. A famous episode in the history of the Riemann Hypothesis is Freeman Dyson’s observation that the zeroes of the zeta function appear to obey statistical laws arising from the theory of random matrices, which had first been studied in theoretical physics.
In 1916, during his time in Cambridge, Ramanujan wrote down an analogue of the Riemann zeta function, inspired by his work on the number of ways of expressing a given number as a sum of squares (a problem with a rich classical history), and made some conjectures as to its properties, which have turned out to be related to many of the most exciting developments in number theory in the last century. Actually, there are a whole family of zeta functions, the properties of which control the statistics of the sums of squares problem. Thorne's work, recognised in the prize citation, essentially shows for Ramanujan’s zeta functions what Riemann proved for his zeta function in 1859.
Taking a broader view, Ramanujan’s zeta functions are now seen to fit into the framework of the Langlands Program. This is a series of conjectures, made by Langlands in the 1960’s, which have been described as a “grand unified theory of mathematics”, and which can be used to explain any number of phenomena in number theory. Another famous example is Wiles proof, in 1994, of Fermat’s Last Theorem. Nowadays the essential piece of Wiles’ work is seen as progress towards a small part of the Langlands program. Thorne's work establishes part of Langlands’ conjectures for a class of objects including Ramanujan’s Delta function.
"I am deeply honoured to be awarded the New Horizons Prize for my work in number theory," said Thorne. "Number theory is a subject with a rich history in Cambridge and I feel very fortunate to be able to make my own contribution to this tradition."
For the tenth year, the Breakthrough Prize recognises the world’s top scientists. Each prize is US $3 million and presented in the fields of Life Sciences, Fundamental Physics (one per year) and Mathematics (one per year). In addition, up to three New Horizons in Physics Prizes, up to three New Horizons in Mathematics Prizes and up to three Maryam Mirzakhani New Frontiers Prizes are given out to early-career researchers each year, each worth US $100,000. The Breakthrough Prizes were founded by Sergey Brin, Priscilla Chan and Mark Zuckerberg, Yuri and Julia Milner, and Anne Wojcicki.
Four University of Cambridge researchers – Professors Shankar Balasubramanian, David Klenerman, Suchitra Sebastian and Jack Thorne – have been recognised by the Breakthrough Prize Foundation in recognition of their outstanding achievements.
AwardsCancerPhysicsmathematicsGenomicsShankar BalasubramanianDavid KlenermanSuchitra E. SebastianJack ThorneYusuf Hamied Department of ChemistryDepartment of PhysicsCavendish LaboratoryDepartment of Pure Mathematics and Mathematical StatisticsFaculty of MathematicsSchool of the Physical SciencesCancer Research UK Cambridge InstituteSchool of Clinical MedicineTrinity CollegeChrist's CollegeFitzwilliam CollegeTrinity HallL-R: Millennium Technology Prize, Nick Saffell, Jack ThorneL-R: David Klenerman, Shankar Balasubramanian, Suchitra Sebastian, Jack Thorne
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Spread of Delta SARS-CoV-2 variant driven by combination of immune escape and increased infectivity
The Delta variant of SARS-CoV-2, which has become the dominant variant in countries including India and the UK, has most likely spread through its ability to evade neutralising antibodies and its increased infectivity, say an international team of researchers.
The findings are reported today in Nature.
As SARS-CoV-2 replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect. One such variant, labelled the B.1.617.2 Delta variant, was first observed in India in late 2020. It has since spread around the globe – in the UK, it is responsible nearly all new cases of coronavirus infection.
Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, one of the study’s senior authors, said: “By combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variants. There’s also evidence that neutralising antibodies produced as a result of previous infection or vaccination are less effective at stopping this variant.
“These factors are likely to have contributed to the devastating epidemic wave in India during the first quarter of 2021, where as many as half of the cases were individuals who had previously been infected with an earlier variant.”
To examine how well the Delta variant was able to evade the immune response, the team extracted serum from blood samples collected as part of the COVID-19 cohort of the NIHR BioResource. The samples came from individuals who had previously been infected with the coronavirus or who had been vaccinated with either the Oxford/AstraZeneca or Pfizer vaccines. Serum contains antibodies raised in response to infection or vaccination. The team found that the Delta variant virus was 5.7-fold less sensitive to the sera from previously-infected individuals, and as much as eight-fold less sensitive to vaccine sera, compared with the Alpha variant - in other words, it takes eight times as many antibodies from a vaccinated individual to block the virus.
Consistent with this, an analysis of over 100 infected healthcare workers at three Delhi hospitals, nearly all of whom had been vaccinated against SARS-CoV-2, found the Delta variant to be transmitted between vaccinated staff to a greater extent than the alpha variant.
SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.
Using 3D airway organoids – ‘mini-organs’ grown from cells from the airway, which mimic its behaviour – the team studied what happens when the virus reaches the respiratory tract. Working under secure conditions, the team used both a live virus and a ‘pseudotyped virus’ – a synthetic form of the virus that mimicked key mutations on the Delta variant – and used this to infect the organoids. They found that the Delta variant was more efficient at breaking into the cells compared with other variants as it carried a larger number of cleaved spikes on its surface. Once inside the cells, the variant was also better able to replicate. Both of these factors give the virus a selection advantage compared to other variants, helping explain why it has become so dominant.
Dr Partha Rakshit from the National Centre for Disease Control, Delhi, India, joint senior author, said: “The Delta variant has spread widely to become the dominant variants worldwide because it is faster to spread and better at infecting individuals than most other variants we’ve seen. It is also better at getting around existing immunity – either through previous exposure to the virus or to vaccination – though the risk of moderate to severe disease is reduced in such cases.”
Professor Anurag Agrawal from the CSIR Institute of Genomics and Integrative Biology, Delhi, India , joint senior author, added: “Infection of vaccinated healthcare workers with the Delta variant is a significant problem. Although they themselves may only experience mild COVID, they risk infecting individuals who have suboptimal immune responses to vaccination due to underlying health conditions – and these patients could then be at risk of severe disease. We urgently need to consider ways of boosting vaccine responses against variants among healthcare workers. It also suggests infection control measures will need to continue in the post-vaccine era.”
The research was largely supported in India by the Ministry of Health and Family Welfare, the Council of Scientific and Industrial Research, and the Department of Biotechnology; and in the UK by Wellcome, the Medical Research Council and the National Institute of Health Research.
Reference:
Micochova, P & Kemp, S et al. SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough. Nature; 6 Sept 2021; DOI: 10.1038/s41586-021-03944-y
Findings suggest infection control measures against variants will need to continue in the post-vaccination era.
COVID-19CoronavirusPublic healthInfectious diseaseshealthRavindra GuptaCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)School of Clinical MedicineBy combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variantsRavi Gupta Fusion Medical Animation via UnsplashVisualisation of the Covid-19 virus
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Going up: birds and mammals evolve faster if their home is rising
Researchers at the University of Cambridge have combined reconstructions of the Earth’s changing surface elevations over the past three million years with data on climate change over this timeframe, and with bird and mammal species’ locations. Their results reveal how species evolved into new ones as land elevation changed - and disentangle the effects of elevation from the effects of climate.
The study found that the effect of elevation increase is greater than that of historical climate change, and of present-day elevation and temperature, in driving the formation of new species – ‘or speciation’.
In contrast to areas where land elevation is increasing, elevation loss was not found to be an important predictor of where speciation happens. Instead, present-day temperature is a better indicator of speciation in these areas.
The results are published today in the journal Nature Ecology and Evolution.
“Often at the tops of mountains there are many more unique species that aren’t found elsewhere. Whereas previously the formation of new species was thought to be driven by climate, we’ve found that elevation change has a greater effect at a global scale,” said Dr Andrew Tanentzap in the University of Cambridge’s Department of Plant Sciences, senior author of the paper.
As land elevation increases, temperature generally decreases and habitat complexity increases. In some cases, for example where mountains form, increasing elevation creates a barrier that prevents species moving and mixing, so populations become reproductively isolated. This is the first step towards the formation of new species.
The effect of increasing elevation on that rate of new species formation over time was more pronounced for mammals than for birds; the researchers think this is because birds can fly across barriers to find mates in other areas. Birds were affected more by present-day temperatures; in birds, variation in temperature creates differences in the timing and extent of mating, risking reproductive isolation from populations of the same species elsewhere.
Until now, most large-scale studies into the importance of topography in generating new species have only considered present-day land elevation, or elevation changes in specific mountain ranges.
“It’s surprising just how much effect historical elevation change had on generating the world’s biodiversity – it has been much more important than traditionally studied variables like temperature. The rate at which species evolved in different places on Earth is tightly linked to topography changes over millions of years,” said Dr Javier Igea in the University of Cambridge’s Department of Plant Sciences, first author of the paper.
He added: “This work highlights important arenas for evolution to play out. From a conservation perspective these are the places we might want to protect, especially given climate change. Although climate change is happening over decades, not millions of years, our study points to areas that can harbour species with greater potential to evolve.”
The researchers say that as the Earth’s surface continues to rise and fall, topography will remain an important driver of evolutionary change.
This research was funded by Wellcome, the Gatsby Charitable Foundation and the Isaac Newton Trust.
Reference
Igea, J. & Tanentzap, A.J.: ‘Global topographic uplift has elevated speciation in mammals and birds over the last 3 million years.’ Nature Ecology & Evolution, September 2021. DOI: 10.1038/s41559-021-01545-6
The rise and fall of Earth’s land surface over the last three million years shaped the evolution of birds and mammals, a new study has found, with new species evolving at higher rates where the land has risen most.
evolutionAndrew TanentzapJavier IgeaDepartment of Plant SciencesSchool of the Biological SciencesWhereas previously the formation of new species was thought to be driven by climate, we’ve found that elevation change has a greater effect at a global scaleAndrew Tanentzap Pablo Heimplatz on UnsplashWild Kea, New Zealand
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New mechanism preventing toxic DNA lesions opens up therapeutic avenues for Huntington's disease
Researchers say the breakthrough study, published in Cell Reports, could lead to much needed therapies for the rare genetic disease, which is currently incurable.
Huntington's disease is a progressive and devastating neurodegenerative disorder that affects about 1 in 10,000 people in the UK.
The disease is caused by the accumulation of toxic repetitive expansions of three DNA blocks called nucleotides (C, A and G) in the huntingtin (HTT) gene and is often termed a repeat expansion disorder. These CAG tri-nucleotide repeats are expanding by misuse of a cellular machinery that usually promotes DNA repair called ‘mismatch repair’. This overuse in mismatch repair drives Huntington's disease onset and progression.
In this study researchers investigated the role of FAN1 - a DNA repair protein that has been identified as a modifier of Huntington’s disease in several genetic studies; however, the mechanism affecting disease onset has remained elusive.
Using human cells and techniques that can read DNA repeat expansions, the researchers found that FAN1 can block the accumulation of the DNA mismatch repair factors to stop repeat expansion thus alleviating toxicity in cells derived from patients.
Co-lead authors Dr Rob Goold and PhD researcher Joseph Hamilton, both UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL, said: “Evidence for DNA repair genes modifying Huntington's disease has been mounting for years. We show that new mechanisms are still waiting to be discovered, which is good news for patients.”
Medicines that could mimic or potentiate (increase the power of) FAN1 inhibition of mismatch repair would alter disease course. The team is now working with the biotechnology company Adrestia Therapeutics, based at the Babraham Research Campus near Cambridge, to translate these discoveries into therapies for substantial numbers of patients in the UK and worldwide.
Senior author of the study, Professor Sarah Tabrizi, director of the UCL Huntington’s Disease Centre, UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL, stated: “Our next step is to determine how important this interaction is in more physiological models and examine if it is therapeutically tractable. We are now working with key pharma partners to try and develop therapies that target this mechanism and might one day reach the clinic.”
Joint senior author, Dr Gabriel Balmus from the UK Dementia Research Institute at the University of Cambridge, said: "There are currently more than fifty CAG repeat expansion disorders that are incurable. If viable, the field suggests that resulting therapies could be applied not only to Huntington's disease but to all the other repeat expansion disorders.”
Professor Steve Jackson, CSO and Interim CEO of Adrestia, said: “My colleagues and I are delighted to be working with Professor Tabrizi, Dr Balmus and the UK Dementia Research Institute to seek ways to translate their exciting science towards new medicines for Huntington's disease and potentially also other DNA-repeat expansion disorders.”
The study was funded by the CHDI Foundation and UK Dementia Research Institute.
Reference
Goold, R et al. FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington’s disease. Cell Reports; 31 August 2021; DOI: 10.1016/j.celrep.2021.109649
Adapted from a press release by UCL
A new mechanism that stops the progression of Huntington’s disease in cells has been identified by scientists at the University of Cambridge and UCL, as part of their research groups at the UK Dementia Research Institute.
NeurosciencedementiaHuntington's DiseaseGabriel BalmusUK Dementia Research InstituteCHDI FoundationSchool of Clinical MedicineUK Dementia Research InstituteThere are currently more than fifty CAG repeat expansion disorders that are incurable. If viable, the field suggests that resulting therapies could be applied not only to Huntington's disease but to all the other repeat expansion disordersGabriel BalmusqimonoDNA jigsaw
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Patients with SARS-CoV-2 Delta variant were more likely to be admitted to hospital compared to patients with Alpha variant
In a new study published in The Lancet Infectious Diseases, researchers at Public Health England and the MRC Biostatistics Unit, University of Cambridge, found that the estimated risk of hospital admission was two times higher for individuals diagnosed with the Delta variant of the SARS-CoV-2 virus, compared to those with the Alpha variant, after adjusting for differences in age, sex, ethnicity, deprivation, region of residence, date of positive test and vaccination status. When broadening the scope to look at the risk of either hospital admission or emergency care attendance, the risk was 1.45 times higher for Delta than Alpha.
This is the largest study to date to report on the risk of hospitalisation outcomes for cases with the Delta compared to the Alpha variant, using 43,338 Alpha and Delta cases confirmed through whole-genome sequencing who tested positive for COVID-19 between 29th March and 23rd May 2021. It is crucial to note that most of the Alpha and Delta cases in the study were unvaccinated or only partially vaccinated: 74% were unvaccinated, 24% were partially vaccinated, and only 2% were fully vaccinated. The results from this study therefore primarily tell us about the risk of hospital admission for those who are unvaccinated or partially vaccinated. Given the small number of hospitalised vaccinated cases, it has not been possible to estimate reliably if the hospitalisation risk differed between Delta and Alpha cases who had been fully vaccinated.
The Delta variant is now the most common SARS-CoV-2 lineage in several higher-income and lower-income countries on all continents, currently accounting for more than 99% of new cases in England [2]. The evidence provided in this study therefore has implications for healthcare practice, planning and response in countries with ongoing or future Delta variant outbreaks, particularly in unvaccinated or partially vaccinated populations. As previous studies have shown Delta and Alpha spread more rapidly than previous variants [2–4], the combination of faster transmission and the current study’s finding of higher risk of severe disease requiring hospital admission in unvaccinated populations implies a more severe burden on healthcare of Delta outbreaks than of Alpha epidemics.
Previous studies have shown the available COVID-19 vaccines are highly effective against symptomatic infections with the Alpha variant [5], and are effective against symptomatic infections with the Delta variant, particularly after a full vaccination cycle with two doses [6,7]. For those who despite vaccination become infected, the vaccination protects against admission to hospital [8].
Dr Anne Presanis, Senior Statistician at the MRC Biostatistics Unit said:
"Our analysis highlights that in the absence of vaccination, any Delta outbreaks will impose a greater burden on healthcare than an Alpha epidemic. Getting fully vaccinated is crucial for reducing an individual’s risk of symptomatic infection with Delta in the first place, and, importantly, of reducing a Delta patient’s risk of severe illness and hospital admission.”
Dr Gavin Dabrera, Consultant Epidemiologist at Public Health England, said:
“This study confirms previous findings that people infected with Delta are significantly more likely to require hospitalisation than those with Alpha, although most cases included in the analysis were unvaccinated.
We already know that vaccination offers excellent protection against Delta and as this variant accounts for over 99% of COVID-19 cases in the UK, it is vital that those who have not received two doses of vaccine do so as soon as possible.
It is still important that if you have COVID-19 symptoms, stay home and get a PCR test as soon as possible.”
Reference:
Katherine A Twohig et al. 'Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study.' The Lancet Infectious Diseases (2021). DOI: 10.1016/S1473-3099(21)00475-8
Largest study to date analysing more than 40,000 COVID-19 cases (including a combination of vaccinated and unvaccinated individuals) confirmed by virus genome sequencing finds a two-fold increased risk of hospitalisation from delta versus alpha variant infections.
COVID-19CoronavirusPublic healthvaccinationRisk and uncertaintyInfectious diseasesAnne PresanisPublic Health EnglandMedical Research Council (MRC) Biostatistics UnitSchool of Clinical MedicineGetting fully vaccinated is crucial for reducing an individual’s risk of symptomatic infection with Delta in the first place, and, importantly, of reducing a Delta patient’s risk of severe illness and hospital admissionAnne PresanisSteven Cornfield via UnsplashPatient receives Covid-19 vaccine
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Farmed carnivores may become ‘disease reservoirs’ posing human health risk
Farming large numbers of carnivores, like mink, could allow the formation of undetected ‘disease reservoirs’, in which a pathogen could spread to many animals and mutate to become a risk to human health.
Research led by the University of Cambridge has discovered that carnivores have a defective immune system, which makes them likely to be asymptomatic carriers of disease-causing pathogens.
Three key genes in carnivores that are critical for gut health were found to have lost their function. If these genes were working, they would produce protein complexes called inflammasomes to activate inflammatory responses and fight off pathogens. The study is published today in the journal Cell Reports.
The researchers say that the carnivorous diet, which is high in protein, is thought to have antimicrobial properties that could compensate for the loss of these immune pathways in carnivores – any gut infection is expelled by the production of diarrhoea. But the immune deficiency means that other pathogens can reside undetected elsewhere in these animals.
“We’ve found that a whole cohort of inflammatory genes is missing in carnivores - we didn’t expect this at all,” said Professor Clare Bryant in the University of Cambridge’s Department of Veterinary Medicine, senior author of the paper.
She added: “We think that the lack of these functioning genes contributes to the ability of pathogens to hide undetected in carnivores, to potentially mutate and be transmitted becoming a human health risk.”
Zoonotic pathogens are those that live in animal hosts before jumping to infect humans. The COVID-19 pandemic, thought to originate in a wild animal, has shown the enormous damage that can be wrought by a novel human disease. Carnivores include mink, dogs, and cats, and are the biggest carriers of zoonotic pathogens.
Three genes appear to be in the process of being lost entirely in carnivores: the DNA is still present but it is not expressed, meaning they have become ‘pseudogenes’ and are not functioning. A third gene important for gut health has developed a unique mutation, causing two proteins called caspases to be fused together to change their function so they can no longer respond to some pathogens in the animal’s body.
“When you have a large population of farmed carnivorous animals, like mink, they can harbour a pathogen - like SARS-CoV-2 and others - and it can mutate because the immune system of the mink isn’t being activated. This could potentially spread into humans,” said Bryant.
The researchers say that the results are not a reason to be concerned about COVID-19 being spread by dogs and cats. There is no evidence that these domestic pets carry or transmit COVID-19. It is when large numbers of carnivores are kept together in close proximity that a large reservoir of the pathogen can build up amongst them, and potentially mutate.
This research was funded by Wellcome.
Reference
Digby, Z. et al: ‘Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.’ Cell Reports, August 2021. DOI: 10.1016/j.celrep.2021.109614
Carnivorous animals lack key genes needed to detect and respond to infection by pathogens, a study has found.
Infectious diseasesCOVID-19Clare BryantDepartment of Veterinary MedicineCambridge Infectious DiseasesDepartment of MedicineQueens' CollegeSchool of the Biological SciencesSchool of Clinical MedicineWe’ve found that a whole cohort of inflammatory genes is missing in carnivores Clare Bryant Oikeutta elaimille on FlickrFarmed mink
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Female scientists lead Cambridge success in Royal Society awards
Burnell is one of twelve former and current Cambridge researchers, including six women, to be recognised in 2021 for their exceptional research and outstanding contributions to science.
Dame Jocelyn has been honoured for her work on the discovery of pulsars in the 1960s while she was a postgraduate student at New Hall (now Murray Edwards College) carrying out research at Cambridge's Cavendish Laboratory.
Past winners of the Copley Medal have included Charles Darwin, Albert Einstein and Dorothy Crowfoot Hodgkin. Dame Jocelyn said: “I am delighted to be the recipient of this year’s Copley Medal, a prize which has been awarded to so many incredible scientists.
“With many more women having successful careers in science, and gaining recognition for their transformational work, I hope there will be many more female Copley winners in the near future.
“My career has not fitted a conventional – male – pattern. Being the first person to identify pulsars would be the highlight of any career; but I have also swung sledgehammers and built radio telescopes; set up a successful group of my own studying binary stars; and was the first female president of the Institute of Physics and of the Royal Society of Edinburgh.
“I hope that my work and presence as a senior woman in science continues to encourage more women to pursue scientific careers”.
The Copley Medal award includes a £25,000 gift which Dame Jocelyn will add to the Institute of Physics' Bell Burnell Graduate Scholarship Fund, which provides grants to graduate students from under-represented groups in physics.
Three female scientists currently working at Cambridge have been recognised in 2021. Professor Sadaf Farooqi from the MRC Metabolic Diseases Unit receives the Croonian Medal and Lecture, together with Sir Stephen O'Rahilly, for their seminal discoveries regarding the control of human body weight, resulting in novel diagnostics and therapies, which improve human health.
Dr Serena Nik-Zainal from the MRC Cancer Unit has been awarded the Francis Crick Medal and Lecture, for her contributions to understanding the aetiology of cancers by her analyses of mutation signatures in cancer genomes, which is now being applied to cancer therapy.
Professor Anne Ferguson-Smith from the Department of Genetics and currently the University’s Pro-Vice-Chancellor for Research receives the Buchanan Medal, for her pioneering work in epigenetics, her interdisciplinary work on genomic imprinting, the interplay between the genome and epigenome, and how genetic and environmental influences affect development and human diseases.
Former Cavendish Laboratory Research Fellow, Professor Michelle Simmons, has won the Bakerian Medal and Lecture, for her seminal contributions to our understanding of nature at the atomic-scale by creating a sequence of world-first quantum electronic devices in which individual atoms control device behaviour.
Professor Frances Kirwan, alumna and Honorary Fellow of Clare College, received the Sylvester Medal, for her research on quotients in algebraic geometry, including links with symplectic geometry and topology, which has had many applications.
Other current Cambridge researchers honoured include Dr Sjors Scheres from the MRC Laboratory of Molecular Biology. Scheres has been awarded the Leeuwenhoek Medal and Lecture for his ground-breaking contributions and innovations in image analysis and reconstruction methods in electron cryo-microscopy, enabling the structure determination of complex macromolecules of fundamental biological and medical importance to atomic resolution.
Emeritus Professor Michael Green from the Department of Applied Mathematics and Theoretical Physics has been awarded Royal Medal A for crucial and influential contributions to the development of string theory over a long period, including the discovery of anomaly cancellation.
The Royal Society’s President, Sir Adrian Smith, said: “Through its medals and awards the Royal Society recognises those researchers and science communicators who have played a critical part in expanding our understanding of the world around us.”
“From advancing vaccine development to catching the first glimpses of distant pulsars, these discoveries shape our societies, answer fundamental questions and open new avenues for exploration.”
Find the full list of 2021 Royal Society medal, award and prize winners here.
Professor Dame Jocelyn Bell Burnell has become only the second woman to be awarded the Royal Society’s prestigious Copley Medal, the world’s oldest scientific prize.
Royal SocietyWomen in STEMMJocelyn Bell BurnellAnne Ferguson-SmithStephen O’RahillySadaf FarooqiMichael GreenSerena Nik-ZainalSjors ScheresRoyal SocietyCavendish LaboratoryMRC Cancer UnitMRC Laboratory of Molecular BiologyDepartment of Applied Mathematics and Theoretical PhysicsMRC Metabolic Diseases UnitDepartment of GeneticsMurray Edwards CollegeChurchill CollegeSchool of the Physical SciencesSchool of the Biological SciencesI hope there will be many more female Copley winners in the near futureJocelyn Bell Burnellhttps://www.youtube.com/watchProfessor Dame Jocelyn Bell Burnell
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Hospital-acquired COVID-19 tends to be picked up from other patients, not from healthcare workers
The study provides previously unprecedented detail on how infections might spread in a hospital context, showing that a minority of individuals can cause most of the transmission.
The researchers analysed data from the first wave of the pandemic, between March and June 2020. While a great deal of effort is made to prevent the spread of viruses within hospital by keeping infected and non-infected individuals apart, this task is made more difficult during times when the number of infections is high. The high level of transmissibility of the virus and the potential for infected individuals to be asymptomatic both make this task particularly challenging.
Looking back at data from the first wave, researchers identified five wards at Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust, where multiple individuals, including patients and healthcare workers, tested positive for COVID-19 within a short space of time, suggesting that a local outbreak might have occurred.
Using new statistical methods that combine viral genome sequence data with clinical information about the locations of individuals, the researchers identified cases where the data were consistent with transmission occurring between individuals in the hospital. Looking in detail at these transmission events highlighted patterns in the data.
The results of the study, published today in eLife, showed that patients who were infected in the hospital were mostly infected by other patients, rather than by hospital staff. Out of 22 cases where patients were infected in hospital, 20 of these were the result of the virus spreading from patients to other patients
Dr Chris Illingworth, a lead author on the study, who carried out his research while at Cambridge’s MRC Biostatistics Unit, said: “The fact that the vast majority of infections were between patients suggests that measures taken by hospital staff to prevent staff transmitting the virus to patients, such as the wearing of masks, were likely to have been effective.
“But it also highlights why it is important that patients themselves are screened for COVID-19 regularly, even if asymptomatic, and wear face masks where possible.”
The study found contrasting results among healthcare workers, who were almost as likely to be infected by patients as they were by other healthcare workers. This was one piece of evidence that motivated the decision to upgrade the respiratory protection worn by healthcare workers in COVID-19 wards at CUH. A recent Cambridge study indicated that this resulted in staff being better protected against catching COVID-19.
The researchers also found a trend towards individuals either infecting no one else, or infecting multiple other people – just over a fifth of patients (21%) caused 80% of the infections. This phenomenon is sometimes called ‘superspreading’ and can make infection control very challenging. Whether or not an individual can be identified in advance as being more or less likely to pass on the virus is an ongoing topic of research.
Dr William Hamilton, an infectious diseases clinician at CUH and co-lead author on the study said: “Preventing new cases of hospital-based infection is a critical part of our work. Here we have shown that analysing clinical and viral genome sequence data can produce insights that inform infection control measures, which are so important for protecting patients and healthcare workers alike.”
The research was funded by COG-UK, Wellcome, the Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.
Reference
Illingworth, CJR & Hamilton, WL et al. Superspreaders drive the largest outbreaks of hospital onset COVID-19 infections. eLife; 24 Aug 2021; DOI: 10.7554/eLife.67308
The majority of patients who contracted COVID-19 while in hospital did so from other patients rather than from healthcare workers, concludes a new study from researchers at the University of Cambridge and Addenbrooke’s Hospital.
COVID-19CoronavirusGenomicshealthcareChris IllingworthWilliam HamiltonWellcomeThe Academy of Medical SciencesHealth FoundationNIHR Cambridge Biomedical Research CentreSchool of Clinical MedicineCOVID-19 Genomics UK (COG-UK) ConsortiumAddenbrooke's HospitalCambridge University Hospitals NHS Foundation TrustDepartment of MedicineThe fact that the vast majority of infections were between patients suggests that measures taken by hospital staff to prevent staff transmitting the virus to patients, such as the wearing of masks, were likely to have been effectiveChris Illingworth Preventing hospital acquired Covid-19 infection | Estée Torok outsideclickCoronavirus
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10,000 autistic people to take part in the UK’s largest study of autism
Spectrum 10K is led by researchers at the world-leading Autism Research Centre (ARC), the University of Cambridge, together with the Wellcome Sanger Institute and University of California Los Angeles (UCLA) and will study how biological and environmental factors impact on the wellbeing of autistic individuals.
In the UK, there are approximately 700,000 autistic individuals. The level of support needed by autistic individuals varies considerably. Many autistic people have additional physical health conditions such as epilepsy, or mental health conditions such as anxiety or depression.
It is unclear what gives rise to the diversity within the autism spectrum or why some autistic people have better outcomes than others. The project aims to answer this question and to identify what support works best for each individual.
Professor Simon Baron-Cohen, leading Spectrum 10K and Director of the ARC, explained: “There is an urgent need to better understand the wellbeing of autistic individuals. Spectrum 10K hopes to answer questions such as why some autistic people have epilepsy or poor mental health outcomes and others do not.”
Individuals of all ages, genders, ethnicities and intellectual capacities will take part in Spectrum 10K. Eligible participants join by completing an online questionnaire and providing a DNA saliva sample by post. Autistic participants involved in Spectrum 10K can also invite their biological relatives (autistic or otherwise) to participate. Information collected from the questionnaire and DNA saliva sample, and information from health records will be used to increase knowledge and understanding of wellbeing in autism.
Dr James Cusack, CEO of the autism research charity Autistica and an autistic person, said: “We are delighted to support Spectrum 10K. This project enables autistic people to participate in and shape autism research to build a future where support is tailored to every individual’s needs.”
The Spectrum 10K team views autism as an example of neurodiversity and is opposed to eugenics or looking for a cure for preventing or eradicating autism itself. Instead, their research aims to identify types of support and treatment which alleviate unwanted symptoms and co-occurring conditions that cause autistic people distress.
The Spectrum 10K team collaborates with an Advisory Panel consisting of autistic individuals, parents of autistic children, clinicians, and autism charity representatives to ensure Spectrum 10K is designed in a way that best serves the autistic community. 27 specialist NHS sites around the UK are also helping with recruitment for Spectrum 10K.
Dr Venkat Reddy, Consultant Neurodevelopmental Paediatrician in the Community Child Health Services at Cambridgeshire and Peterborough NHS Foundation Trust, said: “There is a need to conduct further research into autism and co-occurring conditions to enable researchers and clinicians to build a better understanding of autism. I would encourage autistic individuals and their families to consider taking part in Spectrum 10K.”
Chris Packham, naturalist and TV presenter who is also autistic, said: “I’m honoured to be an ambassador of Spectrum 10K because I believe in the value of science to inform the support services that autistic kids and adults will need.”
Paddy McGuinness, actor, comedian, television presenter, and father of three autistic children, said: “As a parent of three autistic children, I am really excited to support Spectrum 10K. This research is important to help us understand what makes every autistic person different, and how best to support them.”
Dr Anna and Alastair Gadney, parents of a teenager with autism and learning difficulties: “We have been exploring, over many years, how to implement the best support for our son. We wholeheartedly endorse Spectrum 10K and hope our involvement can help increase understanding of autism and in-turn support many families out there.”
Recruitment for Spectrum 10K is now open. Autistic children under the age of 16 must be registered by their parent or legal guardian. Autistic adults who lack the capacity to consent by themselves must be registered by a carer/or family member. To register, participants should visit www.spectrum10k.org
An ambitious new research project, Spectrum 10K, launches today and will recruit 10,000 autistic individuals, as well as their relatives, living in the UK.
Spotlight on neuroscienceautismgeneticsSimon Baron-CohenWellcome Sanger InstituteUniversity of California Los AngelesSchool of Clinical MedicineAutism Research CentreDepartment of PsychiatryThere is an urgent need to better understand the wellbeing of autistic individuals. Spectrum 10K hopes to answer questions such as why some autistic people have epilepsy or poor mental health outcomes and others do notSimon Baron-CohenSpectrum 10kSpectrum 10k image
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Integrated conservation strategies could simultaneously meet biodiversity, climate, and water objectives
To halt the decline of nature and meet Paris Agreement objectives, strategies must be designed and implemented to better manage land use for agriculture, infrastructure, biodiversity conservation, climate change mitigation and adaptation, water provision, and other needs.
A new paper by the Nature Map consortium, published today in the journal Nature Ecology and Evolution, presents an approach for spatial planning to support such integrated conservation strategies.
The study demonstrates that by jointly considering biodiversity, carbon, and water, synergies can be gained from conservation efforts compared to placing emphasis on any individual asset alone. Through strategic action in selected locations, significant benefits can be achieved across all three dimensions. However, conservation efforts need to be greatly scaled-up to meet global biodiversity and climate objectives.
The paper sets out to determine areas of global importance to manage for conservation that would simultaneously protect the greatest number of species from extinction, conserve vulnerable terrestrial carbon stocks, and safeguard freshwater resources.
This work is the first of its kind to truly integrate biodiversity, carbon, and water conservation within a common approach and a single global priority map.
“To implement post-2020 biodiversity strategies such as the Global Biodiversity Framework, policymakers and governments need clarity on where resources and conservation management could bring the greatest potential benefits to biodiversity,” said lead author Martin Jung, a researcher in the IIASA Biodiversity, Ecology, and Conservation Research Group.
He added: “Biodiversity should not be looked at in isolation. Other aspects such as conserving carbon stocks within natural ecosystems should also be considered, so that synergies and trade-offs can be evaluated when pursuing multiple objectives.”
“This type of approach can support decision makers in prioritising locations for conservation efforts, and shows just how much both people and nature could gain,” said Lera Miles, Principal Technical Specialist – Planning for Places, UN Environment Programme World Conservation Monitoring Centre.
She added “To be successful long-term, these areas must be managed effectively and equitably. That includes respecting the rights of, and empowering indigenous peoples and local communities.”
“Maps for integrated land use planning can accelerate progress towards climate and biodiversity objectives and have many important additional policy uses, including helping to generate finance for natural climate solutions, improving carbon markets, and greening supply chains,” said Guido Schmidt-Traub, an author of the paper who has also written a related commentary in the same issue of Nature Ecology and Evolution.
The global priority maps can be explored interactively on the UN Biodiversity lab to support decision makers and generate insight and impact for conservation and sustainable development.
Reference
Jung, M., et al.: Areas of global importance for conserving terrestrial biodiversity, carbon, and water. Nature Ecology and Evolution. August 2021. DOI: 10.1038/s41559-021-01528-7
Adapted from a press release by The International Institute for Applied Systems Analysis (IIASA).
Managing a strategically chosen 30% of land for conservation could safeguard 70% of all terrestrial plant and vertebrate animal species, while simultaneously conserving around two-thirds of the world’s vulnerable carbon and clean water, according to a new study carried out by the Nature Map Consortium, involving the University of Cambridge.
Biodiversity conservationSustainable EarthMatt LewisThe International Institute for Applied Systems AnalysisDepartment of ZoologySchool of the Biological SciencesThis type of approach can support decision makers in prioritising locations for conservation effortsLera MilesAdam Islaam | International Institute for Applied Systems Analysis (IIASA)Global areas of importance for terrestrial biodiversity, carbon and water (dark blue = highest priority, dark orange = lowest priority)
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Worsening GP shortages in disadvantaged areas likely to widen health inequalities
In a study published today in the BJGP Open, a team from the University of Cambridge looked at the relationship between shortages in the healthcare workforce and levels of deprivation. The team found significantly fewer full time equivalent (FTE) GPs per 10,000 patients in practices within areas of higher levels of deprivation. This inequality has widened slightly over time. By December 2020, there were on average 1.4 fewer FTE GPs per 10,000 patients in the most deprived areas compared to the least deprived areas.
The same was the case for total direct patient care staff (all patient-facing general practice staff excluding GPs and nurses), with 1.5 fewer FTE staff per 10,000 patients in the most deprived areas compared to the least deprived areas.
The lower GP numbers in deprived areas, was compensated, in part, by more nurses.
The analysis used data captured between September 2015 and December 2020 from the NHS Digital General Practice Workforce collection. They compared this workforce data against practice population sizes and levels of deprivation across England.
In addition to their report, the team have today launched an interactive dashboard that maps local-level primary care workforce inequalities to accompany the national-level analysis done in the paper. Clear local-level inequalities in GP distribution can be seen within West, North and East Cumbria, Humber, Coast and Vale, and Coventry and Warwickshire STP (Sustainability and Transformation Plan) areas, among others.
Workforce shortages, especially in primary care, have been a problem for health care systems for some time now, and the gap between the growing demand for services and sufficient staff has been widening. Although the number of consultations in general practice has been increasing, staff numbers have not kept up with demand. The number of GPs relative to the size of population has been decreasing since 2009, and the GP workforce is ageing. Doctors are increasingly working part-time, which suggests that shortages will grow steadily worse.
In 2015, then-Secretary of State for Health Jeremy Hunt promised an additional 5,000 GPs for the NHS by 2020, but this was not achieved. Instead, it is predicted that there will be a shortage of 7,000 GPs by 2024.
Dr John Ford from the Department of Public Health and Primary Care at the University of Cambridge, the study’s senior author, said: “People who live in disadvantaged regions of England are not only more likely to have long-term health problems, but are likely to find it even more difficult to see a GP and experience worse care when they see a GP. This is just one aspect of how disadvantage accumulates for some people leading to poor health and early death.
“There may be some compensation due to increasing number of other health professionals, which may partially alleviate the undersupply of GPs in more socioeconomically disadvantaged areas. But this is not a like-for-like replacement and it is unlikely to be enough.”
The researchers say there are a number of reasons that may account for why GP workforce shortages disproportionately affect practices in areas of higher deprivation. Previous studies have suggested that the primary driver of GP inequality was the opening and closing of practices in more disadvantaged areas, with practice closures increasing in recent years.
Claire Nussbaum, the study’s first author, added: “The government has made reducing health inequalities a core commitment, but this will be challenging with the increasing shortage of GPs in areas of high socioeconomic disadvantage, where health needs are greatest. The primary care staffing inequalities we observed are especially concerning, as they suggest that access to care is becoming increasingly limited where health needs are greatest.
“Addressing barriers to health care access is even more urgent in the context of COVID-19, which has widened pre-existing health and social inequities.”
The researchers say that the imbalance in recruitment of staff within primary care must be addressed by policymakers, who will need to consider why practices and networks in disadvantaged areas are relatively under-staffed, and how this can be reversed. Potential options include increased recruitment to medical school from disadvantaged areas, incentivisation of direct patient care posts in under-staffed areas, enhanced training offers for these roles, and offering practices and networks in under-staffed areas additional recruitment support.
Expanded use of additional roles under the Additional Roles Reimbursement Scheme, designed to provide financial reimbursement for Primary Care Networks to build workforce capacity, may partially alleviate GP workload in overstretched practices, but the report’s authors argue that there is a risk that additional workforce will gravitate to more affluent areas, further perpetuating inequity in primary care staffing.
Dr James Matheson, a GP at Hill Top Surgery in Oldham, said: "People living in socioeconomically disadvantaged areas shoulder a much higher burden of physical and mental health problems but have less access to the GPs who could support them towards better health. For the primary care teams looking after them this means a greater workload with fewer resources - a burnout risk which can further exacerbate the problem.
“General Practice in disadvantaged areas is challenging but also enjoyable and professionally rewarding but now, more than ever, we need to see a more equitable distribution of workforce and resources to ensure it is sustainable."
Reference
Nussbaum, C et al. Inequalities in the distribution of the general practice workforce in England. BJGP Open; 18 Aug 2021; DOI: 10.3399/BJGPO.2021.0066
Areas of high socioeconomic disadvantaged are being worst hit by shortages of GPs, a trend that is only worsening with time and is likely to widen pre-existing health inequalities, say researchers at the University of Cambridge.
health servicesinequalityJohn FordClaire NussbaumSchool of Clinical MedicineDepartment of Public Health and Primary CareThe government has made reducing health inequalities a core commitment, but this will be challenging with the increasing shortage of GPs in areas of high socioeconomic disadvantage, where health needs are greatestClaire NussbaumpunggolzenithGP
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Ageing cuttlefish can remember the details of last week’s dinner
The results, published today in the journal Proceedings of the Royal Society B, are the first evidence of an animal whose memory of specific events does not deteriorate with age.
Researchers from the University of Cambridge, the Marine Biological Laboratory in Woods Hole, Massachusetts, and the University of Caen, conducted memory tests on twenty-four common cuttlefish, Sepia officinalis. Half of these were 10-12 months old - not-quite adult, and the other half were in old age at 22-24 months - equivalent to humans in their 90s.
“Cuttlefish can remember what they ate, where and when, and use this to guide their feeding decisions in the future. What’s surprising is that they don’t lose this ability with age, despite showing other signs of ageing like loss of muscle function and appetite,” said Dr Alexandra Schnell in the University of Cambridge’s Department of Psychology, first author of the paper.
As humans age, we gradually lose the ability to remember experiences that happened at particular times and places – for example, what we had for dinner last Tuesday. This is termed ‘episodic memory’, and its decline is thought to be due to deterioration of a part of the brain called the hippocampus.
Cuttlefish do not have a hippocampus, and their brain structure is dramatically different to ours. The ‘vertical lobe’ of the cuttlefish brain is associated with learning and memory. This does not deteriorate until the last two to three days of the animal’s life, which the researchers say could explain why episodic-like memory is not affected by age in cuttlefish.
To conduct the experiment, the cuttlefish were first trained to approach a specific location in their tank marked with a black and white flag. Then they were trained to learn that two foods they commonly eat were available at specific flag-marked locations and after specific delays. At one spot, the flag was waved and a piece of king prawn, their less preferred food, was provided. Live grass shrimp, which they like more, was provided at a different spot where another flag was also waved - but only every three hours. This was repeated for four weeks.
Then the cuttlefishes’ recall of which food would be available, where, and when was tested. To make sure they hadn’t just learned a pattern, the two feeding locations were unique each day. All the cuttlefish - regardless of age - watched which food first appeared at each flag and used that to work out which feeding spot was best at each subsequent flag-waving. This suggests that episodic-like memory does not decline with age in cuttlefish, unlike in humans.
“The old cuttlefish were just as good as the younger ones in the memory task – in fact, many of the older ones did better in the test phase. We think this ability might help cuttlefish in the wild to remember who they mated with, so they don’t go back to the same partner,” said Schnell.
Cuttlefish only breed at the end of their life. By remembering who they mated with, where, and how long ago, the researchers think this helps the cuttlefish to spread their genes widely by mating with as many partners as possible.
Cuttlefish have short lifespans – most live until around two years old – making them a good subject to test whether memory declines with age. Since it is impossible to test whether animals are consciously remembering things, the authors used the term ‘episodic-like memory’ to refer to the ability of cuttlefish to remember what, where and when specific things happened.
This research was funded by the Royal Society and the Grass Foundation.
Reference
Schnell, A.K. et al: ‘Episodic-like memory is preserved with age in cuttlefish.’ Proceedings of the Royal Society B, August 2021. DOI: 10.1098/rspb.2021.1052
Cuttlefish can remember what, where, and when specific things happened - right up to their last few days of life, researchers have found.
animal behaviourZoologyAlex SchnellNicola ClaytonMarine Biological LaboratoryUniversity of CaenDepartment of PsychologySchool of the Biological SciencesThe old cuttlefish were just as good as the younger ones in the memory task Alexandra Schnell Ageing cuttlefish can remember the details of last week’s dinner
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Discovery of origin of oesophageal cancer cells highlights importance of screening for pre-cancerous Barrett’s oesophagus
The study, published today in Science, found that a particular subtype of oesophageal cancer known as oesophageal adenocarcinoma is always preceded by Barrett’s oesophagus – abnormal cells of the oesophagus – even if these cells are no longer visible at the time of cancer diagnosis. This confirms that screening for Barrett’s is an important approach to oesophageal cancer control.
Cancer of the oesophagus is the sixth most deadly cancer, and oesophageal adenocarcinoma is on the rise in western countries. Scientists and doctors have known for some time that the development of this cancer is linked with Barrett’s oesophagus, which shows up in endoscopy as a pink ‘patch’ in the surface of oesophagus and affects around one out of every 100 to 200 people in the United Kingdom – and between 3 and 13 people out of 100 with this condition will go on to develop oesophageal adenocarcinoma in their lifetime. However, the question of where these abnormal cells come from has been a mystery that has baffled scientists for decades.
A multidisciplinary group of scientists led by Professor Rebecca Fitzgerald at the Medical Research Council Cancer Unit, University of Cambridge, today provides the most comprehensive explanation to date.
Dr Lizhe Zhuang, joint first author of the study, said: “It’s intriguing that, although Barrett’s oesophagus predominately occurs in the lower part of oesophagus close to stomach, it has so-called ‘goblet cells’ resembling a much more distant organ, the small intestine. Over the past twenty years there have been at least six different hypotheses about the origin of Barrett’s oesophagus. Using the latest techniques, we believe we have arrived at an answer to this mystery.”
The research team analysed tissue samples from patients with Barrett’s oesophagus and from organ donors who have never had the condition. The samples were collected as part of the Cambridge Biorepository for Translational Medicine at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust.
Lead authors Dr Karol Nowicki-Osuch and Dr Lizhe Zhuang established a detailed ‘atlas’ of human cells and tissues from all possible origins of Barrett’s oesophagus, including oesophageal submucosal glands, an elusive tissue structure that acts in a similar way to saliva glands and has never before been isolated from fresh human tissue.
The researchers then compared the maps of cells from healthy tissues, Barrett’s oesophagus and oesophageal adenocarcinoma using a number of state-of-the-art molecular technologies. These included single cell RNA sequencing, a powerful technology that enables researchers to investigate the functions of a large number of individual cells. They also looked at methylation profiles –chemical modifications to the DNA of cells in the tissue – and at genetic linage to trace back where a particular cell type originated.
The results showed a striking similarity between stomach cells and Barrett’s oesophagus, suggesting that the cells at the very top of the stomach can be reprogrammed to adopt a new tissue identity, becoming more like intestine cells, and replace the oesophageal cells. Furthermore, in this new study the team showed that two genes, MYC and HNF4A, are the keys that switch the tissue identity from stomach to intestinal cells.
Dr Karol Nowicki-Osuch, joint first author of the study, said: “The techniques we used have shown us the internal processes that happen in the stomach cells when they become Barrett’s. The big question now is: what triggers these genes? It’s likely to be a complex combination of factors that include bile acid reflux (often felt as heartburn) and other risk factors, such as obesity, age, male sex and Caucasian ethnicity.”
Importantly, the researchers found that all oesophageal adenocarcinoma cells begin as stomach cells before transforming into Barrett’s cells and then into cancer cells.
Professor Fitzgerald added: “Even if the pre-cancerous Barrett’s is not visible at the time of cancer diagnosis, our data suggests the cancer cells will have been through this stage. This has been debated for some time, but our conclusion is important as it means that screening for Barrett’s is an important approach to controlling oesophageal cancer.”
Michelle Mitchell, Chief Executive of Cancer Research UK, said, “Today’s insights into the origin of oesophageal adenocarcinoma could help inform future research efforts into how to diagnose this type of cancer early – which is key for improving patient outcomes.
“This research goes hand in hand with other recent successes in early detection such as Cytosponge, the sponge-on a-string test, which we funded to detect Barrett’s in patients with heartburn symptoms.”
Detecting cancer earlier will be a key focus of the Cambridge Cancer Research Hospital, a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge to build a new specialist cancer hospital. The hospital will combine modern NHS clinical space with two new research institutes, including the National Institute for the Early Detection of Cancer, which will lead the way in helping advance early cancer detection techniques.
The research was largely funded by the Medical Research Council, Wellcome and Cancer Research UK.
Further information on oesophageal cancer and Barrett’s oesophagus is available via Cancer Research UK.
Reference
Nowicki-Osuch, K & Zhuang, L et al. Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition. Science; 13 Aug 2021; DOI: 10.1126/science.abd1449
Abnormal cells that go on develop into oesophageal cancer – cancer that affects the tube connecting the mouth and stomach – start life as cells of the stomach, according to scientists at the University of Cambridge.
Canceroesophageal cancerRebecca FitzgeraldKarol Nowicki-OsuchLizhe ZhuangMedical Research CouncilWellcomeCancer Research UK (CRUK)School of Clinical MedicineCancer Research UK Cambridge InstituteCambridge Cancer CentreMedical Research Council (MRC) Cancer UnitThe techniques we used have shown us the internal processes that happen in the stomach cells when they become Barrett’s. The big question now is: what triggers these genes?Karol Nowicki-OsuchAdobe StockMan experiencing heartburn
The text in this work is licensed under a Creative Commons Attribution 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.
AI could detect dementia years before symptoms appear
Dandelion clock (Credit: Ýlona María Rybka)
Dandelion clock (Credit: Ýlona María Rybka)
Artificial intelligence could spot the early signs of dementia from a simple brain scan long before major symptoms appear – and in some cases before any symptoms appear – say Cambridge researchers.Dementias are characterised by the build-up of different types of protein in the brain, which damages brain tissue and leads to cognitive decline. In the case of Alzheimer’s disease, these proteins include beta-amyloid, which forms ‘plaques’, clumping together between neurons and affecting their function, and tau, which accumulates inside neurons.
Molecular and cellular changes to the brain usually begin many years before any symptoms occur. Diagnosing dementia can take many months or even years. It typically requires two or three hospital visits and can involve a range of CT, PET and MRI scans as well as invasive lumber punctures.
A team led by Professor Zoe Kourtzi at the University of Cambridge and Alan Turing Institute has developed machine learning tools that can detect dementia in patients at a very early stage. Using brain scans from patients who went on to develop Alzheimer’s, their machine learning algorithm learnt to spot structural changes in the brain. When combined with the results from standard memory tests, the algorithm was able to provide a prognostic score – that is, the likelihood of the individual having Alzheimer’s disease.
For those patients presenting with mild cognitive impairment – signs of memory loss or problems with language or visual/spatial perception – the algorithm was higher than 80% accurate in predicting those individuals who went on to develop Alzheimer’s disease. It was also able to predict how fast their cognition will decline over time.
MRI brain scan of healthy volunteer (Credit: Timothy Rittman)
MRI brain scan of healthy volunteer (Credit: Timothy Rittman)
MRI brain scan of Alzheimer's patient (Credit: TImothy Rittman)
MRI brain scan of Alzheimer's patient (Credit: TImothy Rittman)
Professor Kourtzi, from Cambridge's Department of Psychology, said: “We have trained machine learning algorithms to spot very early signs of dementia just by looking for patterns of grey matter loss – essentially, wearing away – in the brain. When we combine this with standard memory tests, we can predict whether an individual will show slower or faster decline in their cognition.
“We’ve even been able to identify some patients who were not yet showing any symptoms, but went on to develop Alzheimer’s."
Although the algorithm has been optimised to look for signs of Alzheimer’s disease, Professor Kourtzi and colleagues are now training it to recognise different forms of dementia, each of which has its own characteristic pattern of volume loss.
Dr Timothy Rittman from the Department of Clinical Neurosciences and a consultant at Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust, is now leading a trial to look at whether this approach is useful in a clinical setting.
“We’ve shown that this approach works in a research setting – we now need to test it in a ‘real world’ setting,” explained Dr Rittman.
To date around 80 patients have taken part in the trial, which was run by CUH, Cambridgeshire and Peterborough NHS Foundation Trust and two NHS trusts in Brighton.
Catching dementia early is important for several reasons, explained Dr Rittman. “When patients begin to experience memory and cognitive problems, this can understandably be a very difficult time. Being able to provide an accurate diagnosis gives them clarity and, depending on the diagnosis, can either ease their minds or help them and their loved ones put preparations in place for the longer term."
“If we catch the disease early enough, there are lifestyle changes we can recommend – blood pressure medication, improved diet and exercise, stopping smoking, for example – that may help slow the progression of the disease.”Dr Timothy RittmanThere are currently very few drugs available to help treat dementia. One of the reasons that clinical trials often fail is thought to be because once a patient has developed symptoms, it may be too late to make a major difference. Having the ability to identify individuals at a very early stage could therefore help researchers develop new medicines.
If the trial is successful, the algorithm could be rolled out to thousands more patients across the country.
Living with Alzheimer’s diseaseAddenbrooke’s patient Dennis Clark was one of the first people in the country to take part in the new trial. Before lockdown, the 75-year-old retired sales director had been enjoying his retirement with wife Penny, going on holiday and walking his two dogs. But Penny soon noticed he was starting to forget things.
“If I asked him to do something, he would do the opposite. Then when we went out for a meal – which we didn’t do for a long time because of lockdown – he couldn’t remember how to pay for anything.”
Penny decided to call the GP for help when Dennis, who had always taken pride in his appearance, started to wear the same clothes over and over again.
“The GP did a quick test over the phone and said Dennis needed to be referred. I had heard Addenbrooke’s had a very comprehensive memory unit, so I was really pleased that we were able to be referred there.
“We had an initial consultation and we were asked if we wanted to go down the research route, which I was really keen for Dennis to do because it doesn’t just help him, it helps others as well.”
Dennis underwent an MRI scan and later that same day he and Penny received the news that his results were consistent with early onset of Alzheimer’s disease. Dennis will begin taking medication to help treat the symptoms of Alzheimer’s disease.
“We are very grateful to Addenbrooke’s and would recommend other people take up trials as well. Quicker diagnosis means Dennis will be able to start medication that will hopefully delay his disease. It also means we can plan for the future and start to accept what is happening.”
Case study courtesy of Cambridge University Hospitals NHS Foundation Trust.
ReferenceGiorgio, J et al. Modelling prognostic trajectories of cognitive decline due to Alzheimer's disease. NeuroImage: Clinical; 26 Jan 2020; DOI: 10.1016/j.nicl.2020.102199
Giorgio, J et al. Predicting future regional tau accumulation in asymptomatic and early Alzheimer’s disease. BioRXiv (pre-print)
Article posted 12 August 2021
TopBuilt with Shorthand Summary:Artificial intelligence could spot the early signs of dementia from a simple brain scan long before major symptoms appear – and in some cases before any symptoms appear – say Cambridge researchers.Artificial intelligence (AI) could spot the early signs of dementia from a simple brain scan long before major symptoms appear – and in some cases before any symptoms appear – say Cambridge researchers.
Image: Affiliation (schools and institutions): School of Clinical MedicineSchool of the Biological SciencesDepartment of Clinical NeurosciencesDepartment of PsychologyAddenbrooke's HospitalCambridge University Hospitals NHS Foundation TrustExternal Affiliations: The Alan Turing InstitutePeople (our academics and staff): Zoe KourtziTimothy RittmanSubject (including Spotlight on ... where applicable): Spotlight on neuroscienceNeurosciencehealthdementiaAlzheimer's diseaseArtificial intelligenceSection: ResearchNews type: FeaturesLab-grown beating heart cells identify potential drug to prevent COVID-19-related heart damage
The heart is one the major organs damaged by infection with SARS-CoV-2, particularly the heart cells, or ‘cardiomyocytes’, which contract and circulate blood. It is also thought that damage to heart cells may contribute to the symptoms of long COVID.
Patients with underlying heart problems are more than four times as likely to die from COVID-19, the disease caused by SARS-CoV-2 infection. The case fatality rate in patients with COVID-19 rises from 2.3% to 10.5% in these individuals.
To gain entry into our cells, SARS-CoV-2 hijacks a protein on the surface of the cells, a receptor known as ACE2. Spike proteins on the surface of SARS-CoV-2 – which give it its characteristic ‘corona’-like appearance – bind to ACE2. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow itself to replicate and spread.
A team of scientists at the University of Cambridge has used human embryonic stem cells to grow clusters of heart cells in the lab and shown that these cells mimic the behaviour of the cells in the body, beating as if to pump blood. Crucially, these model heart cells also contained the key components necessary for SARS-CoV-2 infection – in particular, the ACE2 receptor.
Working in special biosafety laboratories and using a safer, modified synthetic (‘pseudotyped’) virus decorated with the SARS-CoV-2 spike protein, the team mimicked how the virus infects the heart cells. They then used this model to screen for potential drugs to block infection.
Dr Sanjay Sinha from the Wellcome-MRC Cambridge Stem Cell Institute said: “Using stem cells, we’ve managed to create a model which, in many ways, behaves just like a heart does, beating in rhythm. This has allowed us to look at how the coronavirus infects cells and, importantly, helps us screen possible drugs that might prevent damage to the heart.”
The team showed that some drugs that targeted the proteins involved in SARS-CoV-2 viral entry significantly reduced levels of infection. These included an ACE2 antibody that has been shown previously to neutralise pseudotyped SARS-CoV-2 virus, and DX600, an experimental drug.
DX600 is an ACE2 peptide antagonist – that is, a molecule that specifically targets ACE2 and inhibits the activity of peptides that play a role in allowing the virus to break into the cell.
DX600 was around seven times more effective at preventing infection compared to the antibody, though the researchers say this may be because it was used in higher concentrations. The drug did not affect the number of heart cells, implying that it would be unlikely to be toxic.
Professor Anthony Davenport from the Department of Medicine and a fellow at St Catharine’s College, Cambridge said: “The spike protein is like a key that fits into the ‘lock’ on the surface of the cells – the ACE2 receptor – allowing it entry. DX600 acts like gum, jamming the lock’s mechanism, making it much more difficult for the key to turn and unlock the cell door.
“We need to do further research on this drug, but it could provide us with a new treatment to help reduce harm to the heart in patients recently infected with the virus, particularly those who already have underlying heart conditions or who have not been vaccinated. We believe it may also help reduce the symptoms of long COVID.”
The research was largely supported by Wellcome, Addenbrooke’s Charitable Trust, Rosetrees Trust Charity and British Heart Foundation.
Reference
Williams, TL et al. Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection. Communications Biology; 29 Jul 2017; DOI: 10.1038/s42003-021-02453-y
Cambridge scientists have grown beating heart cells in the lab and shown how they are vulnerable to SARS-CoV-2 infection. In a study published in Communications Biology, they used this system to show that an experimental peptide drug called DX600 can prevent the virus entering the heart cells.
Stem cellsCOVID-19Coronavirusheartcardiovascular disease (CVD)Anthony DavenportSanjay SinhaWellcomeAddenbrooke’s Charitable TrustRosetrees TrustBritish Heart FoundationSchool of Clinical MedicineDepartment of MedicineWellcome-MRC Cambridge Stem Cell InstituteDepartment of Experimental Medicine and ImmunotherapeuticsSt Catharine's CollegeUsing stem cells, we’ve managed to create a model which, in many ways, behaves just like a heart does, beating in rhythm. This has allowed us to look at how the coronavirus infects cells and, importantly, helps us screen possible drugs that might prevent damage to the heartSanjay Sinha Beating heart cells infected with virus sbtlneetHeart
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Artificial pancreas trialled for outpatients with type 2 diabetes for first time
Diabetes is the most common cause of kidney failure, accounting for just under a third (30%) of cases. As the number of people living with type 2 diabetes increases, so too does the number of people requiring dialysis or a kidney transplant. Kidney failure increases the risk of hypoglycaemia and hyperglycaemia – abnormally low or high levels of blood sugar respectively – which in turn can cause complications from dizziness to falls and even to coma.
Managing diabetes in patients with kidney failure is challenging for both patients and healthcare professionals. Many aspects of their care are poorly understood, including targets for blood sugar levels and treatments. Most oral diabetes medications are not recommended for these patients, so insulin injections are the most commonly used diabetes therapy – though optimal insulin dosing regimens are difficult to establish.
A team at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust has previously developed an artificial pancreas with the aim of replacing insulin injections for patients living with type 1 diabetes. In research published today in Nature Medicine, the team – working with researchers at Bern University Hospital and University of Bern, Switzerland – has shown that the device can be used to support patients living with both type 2 diabetes and kidney failure.
Unlike the artificial pancreas being used for type 1 diabetes, this version is a fully closed loop system – whereas patients with type 1 diabetes need to tell their artificial pancreas that they are about to eat to allow adjustment of insulin, for example, with this new version they can leave the device to function entirely automatically.
Dr Charlotte Boughton from the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, who led the study, said: “Patients living with type 2 diabetes and kidney failure are a particularly vulnerable group and managing their condition – trying to prevent potentially dangerous highs or lows of blood sugar levels – can be a challenge. There’s a real unmet need for new approaches to help them manage their condition safely and effectively.”
The artificial pancreas is a small, portable medical device designed to carry out the function of a healthy pancreas in controlling blood glucose levels, using digital technology to automate insulin delivery. The system is worn externally on the body, and is made up of three functional components: a glucose sensor, a computer algorithm to calculate the insulin dose, and an insulin pump. Software in the user’s smartphone sends a signal to an insulin pump to adjust the level of insulin the patient receives. The glucose sensor measures the patient’s blood sugar levels and sends these back to the smartphone to enable it to make further adjustments.
The team recruited 26 patients requiring dialysis between October 2019 and November 2020. Thirteen participants were randomised to receive the artificial pancreas first and 13 to receive standard insulin therapy first. The researchers compared how long patients spent in the target blood sugar range (5.6 to 10.0mmol/L) over a 20-day period as outpatients.
Patients using the artificial pancreas spent on average 53% of their time in the target range, compared to 38% when they used the control treatment. This equated to around 3.5 additional hours every day spent in the target range compared with the control therapy.
Mean blood sugar levels were lower with the artificial pancreas (10.1 vs. 11.6 mmol/L). The artificial pancreas reduced the amount of time patients spent with potentially dangerously low blood sugar levels, or ‘hypos’.
The efficacy of the artificial pancreas improved considerably over the study period as the algorithm adapted, and the time spent in the target blood sugar range increased from 36% on day one to over 60% by the twentieth day. This finding highlights the importance of using an adaptive algorithm, which can adjust in response to an individual’s changing insulin requirements over time.
When asked about their experiences of using the artificial pancreas, everyone who responded said they would recommend it to others. Nine out of ten (92%) reported that they spent less time managing their diabetes with the artificial pancreas than during the control period, and similar numbers (87%) were less worried about their blood sugar levels when using it.
Other benefits of the artificial pancreas reported by study participants included less need for finger-prick blood sugar checks, less time required to manage their diabetes resulting in more personal time and freedom, and improved peace of mind and reassurance. Downsides included discomfort wearing the insulin pump and carrying the smartphone.
Senior author Professor Roman Hovorka, also from the Wellcome-MRC Institute of Metabolic Science, said: “Not only did the artificial pancreas increase the amount of time patients spent within the target range for the blood sugar levels, it also gave the users peace of mind. They were able to spend less time having to focus on managing their condition and worrying about their blood sugar levels, and more time getting on with their lives.”
Dr Boughton added: “Now that we’ve shown the artificial pancreas works in one of the more difficult-to-treat groups of patients, we believe it could prove useful in the wider population of people living with type 2 diabetes.”
The team is currently trialling the artificial pancreas for outpatient use in people living with type 2 diabetes who do not need dialysis and exploring the system in complex medical situations such as perioperative care.
Dr Lia Bally, who co-led the study in Bern, said: “The artificial pancreas has the potential to become a key feature of integrated personalised care for people with complex medical needs.”
The research was supported by the NIHR Cambridge Biomedical Research Centre, The Novo Nordisk UK Research Foundation, Swiss Society for Endocrinology and Diabetes, and Swiss Diabetes Foundation and Swiss Kidney Foundation.
Reference
Boughton, CK et al. Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomised crossover trial. Nat Med; 4 Aug 2021; DOI: 10.1038/s41591-021-01453-z
An artificial pancreas could soon help those people living with type 2 diabetes who also require kidney dialysis. Tests led by the University of Cambridge and Inselspital, University Hospital of Bern, Switzerland, show that the device can help patients safely and effectively manage their blood sugar levels and reduce the risk of low blood sugar levels.
type 2 diabetesCharlotte BoughtonRoman HovorkaNIHR Cambridge Biomedical Research CentreNovo Nordisk UK Research FoundationSwiss Society for Endocrinology and DiabetesSwiss Diabetes FoundationSwiss Kidney FoundationSchool of Clinical MedicineWellcome-MRC Institute of Metabolic ScienceCambridge University Hospitals NHS Foundation TrustPatients living with type 2 diabetes and kidney failure are a particularly vulnerable group and managing their condition can be a challenge. There’s a real unmet need for new approaches to help them manage their condition safely and effectivelyCharlotte BoughtonUniversity of CambridgePatient using the artificial pancreas
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Scientists can detect brain tumours using a simple urine or blood plasma test
The team say that a test for detecting glioma using urine is the first of its kind in the world.
Although the research, published in EMBO Molecular Medicine, is in its early stages and only a small number of patients were analysed, the team say their results are promising.
The researchers suggest that in the future, these tests could be used by GPs to monitor patients at high risk of brain tumours, which may be more convenient than having an MRI every three months, which is the standard method.
When people have a brain tumour removed, the likelihood of it returning can be high, so they are monitored with an MRI scan every three months, which is followed by biopsy.
Blood tests for detecting different cancer types are a major focus of research for teams across the world, and there are some in use in the clinic. These tests are mainly based on finding mutated DNA, shed by tumour cells when they die, known as cell-free DNA (cfDNA).
However, detecting brain tumour cfDNA in the blood has historically been difficult because of the blood-brain-barrier, which separates blood from the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord, preventing the passage of cells and other particles, such as cfDNA.
Researchers have previously looked at detecting cfDNA in CSF, but the spinal taps needed to obtain it can be dangerous for people with brain tumours so are not appropriate for patient monitoring.
Scientists have known that cfDNA with similar mutations to the original tumour can be found in blood and other bodily fluids such as urine in very low levels, but the challenge has been developing a test sensitive enough to detect these specific mutations.
The researchers, led by Dr Florent Mouliere who is based at the Rosenfeld Lab of the Cancer Research UK Cambridge Institute and at the Amsterdam UMC, and Dr Richard Mair, who is based at Cancer Research UK Cambridge Institute and the University of Cambridge developed two approaches in parallel to overcome the challenge of detecting brain tumour cfDNA.
The first approach works for patients who have previously had glioma removed and biopsied. The team designed a tumour-guided sequencing test that was able to look for the mutations found in the tumour tissue within the cfDNA in the patient’s urine, CSF, and blood plasma.
A total of eight patients who had suspected brain tumours based on MRIs were included in this part of the study. Samples were taken at their initial brain tumour biopsies, alongside CSF, blood and urine samples.
By knowing where in the DNA strand to look, the researchers found that it was possible to find mutations even in the tiny amounts of cfDNA found in the blood plasma and urine.
The test was able to detect cfDNA in 7 out of 8 CSF samples, 10 out of the 12 plasma blood samples and 10 out of the 16 urine samples.
For the second approach the researchers looked for other patterns in the cfDNA that could also indicate the presence of a tumour, without having to identify the mutations.
They analysed 35 samples from glioma patients, 27 people with non-malignant brain disorders, and 26 healthy people. They used whole genome sequencing, where all the cfDNA of the tumour is analysed, not just the mutations.
They found in the blood plasma and urine samples that fragments of cfDNA, which came from patients with brain tumours were different sizes than those from patients with no tumours in CSF. They then fed this data into a machine learning algorithm which was able to successfully differentiate between the urine samples of people with and without glioma.
The researchers say that while the machine learning test is cheaper and easier, and a tissue biopsy from the tumour is not needed, it is not as sensitive and is less specific than the first tumour-guided sequencing approach.
MRIs are not invasive or expensive, but they do require a trip to the hospital, and the three-month gap between checks can be a regular source of anxiety for patients.
The researchers suggest that their tests could be used between MRI scans, and could ultimately be able to detect a returning brain tumour earlier.
The next stage of this research will see the team comparing both tests against MRI scans in a trial with patients with brain tumours who are in remission to see if it can detect if their tumours are coming back at the same time or earlier than the MRI. If the tests prove that they can detect brain tumours earlier than an MRI, then the researchers will look at how they can adapt the tests so they could be offered in the clinic, which could be within the next ten years.
“We believe the tests we’ve developed could in the future be able to detect a returning glioma earlier and improve patient outcomes,” said Mair. “Talking to my patients, I know the three-month scan becomes a focal point for worry. If we could offer a regular blood or urine test, not only will you be picking up recurrence earlier, you can also be doing something positive for the patient’s mental health.”
Michelle Mitchell, Chief Executive of Cancer Research UK said, “While this is early research, it’s opened up the possibility that within the next decade we could be able to detect the presence of a brain tumour with a simple urine or blood test. Liquid biopsies are a huge area of research interest right now because of the opportunities they create for improved patient care and early diagnosis. It’s great to see Cancer Research UK researchers making strides in this important field.”
Sue Humphreys, from Wallsall, a brain tumour patient, said: "If these tests are found to be as accurate as the standard MRI for monitoring brain tumours, it could be life changing.
If patients can be given a regular and simple test by their GP, it may help not only detect a returning brain tumour in its earliest stages, it can also provide the quick reassurance that nothing is going on which is the main problem we all suffer from, the dreaded Scanxiety.
The problem with three-monthly scans is that these procedures can get disrupted by other things going on, such as what we have seen with the Covid pandemic. As a patient, this causes worry as there is a risk that things may be missed, or delayed, and early intervention is the key to any successful treatment.”
Reference:
Florent Mouliere et al. ‘Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients.’ EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202012881
Adapted from a Cancer Research UK press release.
Researchers from the Cancer Research UK Cambridge Institute have developed two tests that can detect the presence of glioma, a type of brain tumour, in patient urine or blood plasma.
Cancerdiagnosticbrainbrain tumourstumoursFlorent MouliereRichard MairCancer Research UK (CRUK)Cancer Research UK Cambridge InstituteSchool of Clinical Medicine
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Blushing plants reveal when fungi are growing in their roots
This is the first time this vital, 400 million year old process has been visualised in real time in full root systems of living plants. Understanding the dynamics of plant colonisation by fungi could help to make food production more sustainable in the future.
Almost all crop plants form associations with a particular type of fungi – called arbuscular mycorrhiza fungi – in the soil, which greatly expand their root surface area. This mutually beneficial interaction boosts the plant’s ability to take up nutrients that are vital for growth.
The more nutrients plants obtain naturally, the less artificial fertilisers are needed. Understanding this natural process, as the first step towards potentially enhancing it, is an ongoing research challenge. Progress is likely to pay huge dividends for agricultural productivity.
In a study published in the journal PLOS Biology, researchers used the bright red pigments of beetroot – called betalains – to visually track soil fungi as they colonised plant roots in a living plant.
“We can now follow how the relationship between the fungi and plant root develops, in real-time, from the moment they come into contact. We previously had no idea about what happened because there was no way to visualise it in a living plant without the use of elaborate microscopy,” said Dr Sebastian Schornack, a researcher at the University of Cambridge’s Sainsbury Laboratory and joint senior author of the paper.
To achieve their results, the researchers engineered two model plant species – a legume and a tobacco plant – so that they would produce the highly visible betalain pigments when arbuscular mycorrhiza fungi were present in their roots. This involved combining the control regions of two genes activated by mycorrhizal fungi with genes that synthesise red-coloured betalain pigments.
The plants were then grown in a transparent structure so that the root system was visible, and images of the roots could be taken with a flatbed scanner without disturbing the plants.
Using their technique, the researchers could select red pigmented parts of the root system to observe the fungus more closely as it entered individual plant cells and formed elaborate tree-like structures – called arbuscules – which grow inside the plant’s roots. Arbuscules take up nutrients from the soil that would otherwise be beyond the reach of the plant.
Other methods exist to visualise this process, but these involve digging up and killing the plant and the use of chemicals or expensive microscopy. This work makes it possible for the first time to watch by eye and with simple imaging how symbiotic fungi start colonising living plant roots, and inhabit parts of the plant root system over time.
“This is an exciting new tool to visualise this, and other, important plant processes. Beetroot pigments are a distinctive colour, so they’re very easy to see. They also have the advantage of being natural plant pigments, so they are well tolerated by plants,” said Dr Sam Brockington, a researcher in the University of Cambridge’s Department of Plant Sciences, and joint senior author of the paper.
Mycorrhiza fungi are attracting growing interest in agriculture. This new technique provides the ability to ‘track and trace’ the presence of symbiotic fungi in soils from different sources and locations. The researchers say this will enable the selection of fungi that colonise plants fastest and provide the biggest benefits in agricultural scenarios.
Understanding and exploiting the dynamics of plant root system colonisation by fungi has potential to enhance future crop production in an environmentally sustainable way. If plants can take up more nutrients naturally, this will reduce the need for artificial fertilisers – saving money and reducing associated water pollution.
This research was funded by the Biotechnology and Biological Sciences Research Council, Gatsby Charitable Foundation, Royal Society, and Natural Environment Research Council.
Reference
Timoneda, A. & Yunusov, T. et al: ‘MycoRed: Betalain pigments enable in vivo real-time visualisation of arbuscular mycorrhizal colonisation.’ PLOS Biology, July 2021. DOI: 10.1371/journal.pbio.3001326
Scientists have created plants whose cells and tissues ‘blush’ with beetroot pigments when they are colonised by fungi that help them take up nutrients from the soil.
plant sciencesGlobal food securitySustainable agricultureSustainable EarthSam BrockingtonSebastian SchornackCambridge University Botanic GardenDepartment of Plant SciencesSainsbury LaboratorySchool of the Biological SciencesWe can now follow how the relationship between the fungi and plant root develops, in real-time, from the moment they come into contact.Sebastian SchornackTemur Yunusov and Alfonso TimonedaCells of roots colonised by fungi turn red
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