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Severe Delhi outbreak highlights challenge of reaching herd immunity in face of Delta variant

Latest Research in Cambridge - Thu, 14/10/2021 - 19:00

SARS-CoV-2 had spread widely throughout India in the first wave, with initial results from the Indian Council of Medical Research finding one in five (21%) adults and one in four (25%) 10 to 17 year old adolescents had been infected. The figures were much higher in Indian megacities: by February 2021, over a half (56%) of individuals in Delhi were thought to have been infected.

Since the first case of COVID-19 was detected in Delhi in March 2020, the city had experienced multiple outbreaks, in June, September and November 2020. After reaching a high of almost 9,000 cases daily in November 2020, new cases steadily declined, with very few new infections between December 2020 and March 2021.

The situation reversed dramatically in April 2021, going from approximately 2,000 daily cases to 20,000 between 31 March and 16 April. This was accompanied by a rapid rise in hospitalisations and ICU admissions, severely stressing the healthcare system, with daily deaths spiking to levels three-fold higher than previous waves. 

In research published today, an international team of scientists used genomic and epidemiological data, together with mathematical modelling, to study the outbreak. The work was led by the National Centre of Disease Control and the CSIR Institute of Genomics and Integrative Biology, India, with collaborators from the University of Cambridge and Imperial College London, UK, and the University of Copenhagen, Denmark.

To determine whether SARS-CoV-2 variants were responsible for the April 2021 outbreak in Delhi, the team sequenced and analysed viral samples from Delhi from the previous outbreak in November 2020 until June 2021. They found that the 2020 outbreaks in Delhi were unrelated to any variant of concern. The Alpha variant (B.1.1.7) was identified only occasionally, primarily in foreign travellers, until January 2021. The Alpha variant increased in Delhi to about 40% of cases in March 2021, before it was displaced by a rapid increase in the Delta variant (B.1.617.2) in April.

Applying mathematical modelling to the epidemiological and genomic data, the researchers found that the Delta variant was between 30-70% more transmissible than previous SARS-CoV-2 lineages in Delhi, including the Alpha variant. Importantly, the model also suggested that the Delta variant was able to infect people who had previously been infected by SARS-CoV-2 – prior infection provided only 50-90% of the protection against infection with Delta variant that it provides against previous lineages.

To look for actual evidence of reinfection to support their modelling work, the researchers examined a cohort of individuals recruited by the Council of Scientific and Industrial Research (CSIR), India. In February, 42.1% of unvaccinated subjects participating in the study had tested positive for antibodies against SARS-CoV-2. In June, the corresponding number was 88.5%, suggesting very high infection rates during the second wave. Among 91 subjects with prior infection before Delta, about one-quarter (27.5%) showed increased levels of antibodies, providing evidence of reinfection.

When the team sequenced all the samples of vaccination-breakthrough cases at a single centre over the period of the study, they found that among 24 reported cases, Delta was seven-fold more likely to lead to vaccination breakthroughs than non-Delta lineages.

Dr Anurag Agrawal from the National Centre of Disease Control and the CSIR Institute of Genomics and Integrative Biology, India, senior author and co-lead investigator, said: “This work helps understand the global outbreaks of Delta, including in highly vaccinated populations, because the Delta variant can transmit through vaccinated or previously infected people to find those who are susceptible.”

Co-author Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, UK, said: “The concept of herd immunity is critical in ending outbreaks, but the situation in Delhi shows that infection with previous coronavirus variants will be insufficient for reaching herd immunity against Delta. The only way of ending or preventing outbreaks of Delta is either by infection with this variant or by using vaccine boosters that raise antibody levels high enough to overcome Delta’s ability to evade neutralisation.”

Previous research led by Professor Gupta showed that the Delta variant has most likely spread through its ability to evade neutralising antibodies and its increased infectivity.

The research was supported by the Indian Ministry of Health and Family Welfare, Council of Scientific and Industrial Research, and Department of Biotechnology.

Reference
Mahesh Dhar, Robin Marwal, Radhakrishnan VS, Kalaiarasan Ponnusamy, Bani Jolly, Rahul  Bhoyar, et al. Genomic characterization and Epidemiology of an emerging SARS-CoV-2 variant in Delhi, India. Science; 14 Oct 2021; DOI: 10.1126/science.abj9932

The severe outbreak of COVID-19 in Delhi, India, in 2021 showed not only that the Delta variant of SARS-CoV2 is extremely transmissible but that it can infect individuals previously infected by a different variant of the coronavirus, say a team of international scientists writing in Science.

COVID-19CoronavirusIndiaInfectious diseasesRavindra GuptaMinistry of Health and Family WelfareCouncil of Scientific and Industrial ResearchDepartment of Biotechnology (DBT)School of Clinical MedicineCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)Cambridge Infectious DiseasesThe concept of herd immunity is critical in ending outbreaks, but the situation in Delhi shows that infection with previous coronavirus variants will be insufficient for reaching herd immunity against DeltaRavi GuptaGovernment of IndiaHealth care workers administering COVID-19 vaccination in New Delhi


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YesLicense type: Attribution-NoncommericalNews type: NewsSuper Tags: Health and Medicine

Mito warriors: how T cell assassins reload their weapons to kill and kill again

Latest Research in Cambridge - Thu, 14/10/2021 - 19:00

Cytotoxic T cells are specialist white blood cells that are trained by our immune system to recognise and eliminate threats – including tumour cells and cells infected with invading viruses, such as SARS-CoV-2, which causes COVID-19. They are also at the heart of new immunotherapies that promise to transform cancer treatment. 

Professor Gillian Griffiths from the Cambridge Institute for Medical Research, who led the research, said: “T cells are trained assassins that are sent on their deadly missions by the immune system. There are billions of them in our blood, each engaged in a ferocious and unrelenting battle to keep us healthy.

“Once a T cell has found its target, it binds to it and releases its toxic cargo. But what is particularly remarkable is that they are then able to go on to kill and kill again. Only now, thanks to state-of-the-art technologies, have we been able to find out how they reload their weapons.”

Today, in a study published in Science, the team have shown that the refuelling of T cells’ toxic weapons is regulated by mitochondria. Mitochondria are often referred to as a cell’s batteries as they provide the energy that power their function. However, in this case the mitochondria use an entirely different mechanism to ensure the killer T cells have sufficient ‘ammunition’ to destroy their targets.

Professor Griffiths added: “These assassins need to replenish their toxic payload so that they can keep on killing without damaging the T cells themselves. This careful balancing act turns out to be regulated by the mitochondria in T cells, which set the pace of killing according to how quickly they themselves can manufacture proteins. This enables killer T cells to stay healthy and keep on killing under challenging conditions when a prolonged response is required.”

Understanding the details of this basic process could ultimately help in the long-term scientific goal of designing and engineering T cells that are better at killing cancer cells, say the researchers. 

To accompany the study, Professor Griffiths and colleagues have released footage showing killer T cells as they hunt down and eliminate cancer cells.

One teaspoon full of blood alone is believed to have around 5 million T cells, each measuring around 10 micrometres in length, about a tenth the width of a human hair. The cells, seen in the video as red or green amorphous ‘blobs’, move around rapidly, investigating their environment as they travel.

When a T cell finds an infected cell or, in the case of the film, a cancer cell, membrane protrusions rapidly explore the surface of the cell, checking for tell-tale signs that this is an uninvited guest. The T cell binds to the cancer cell and injects poisonous ‘cytotoxin’ proteins down special pathways called microtubules to the interface between the T cell and the cancer cell, before puncturing the surface of the cancer cell and delivering its deadly cargo.

The research was funded by Wellcome.

Reference
Lisci, M et al. Mitochondrial translation is required for sustained killing by cytotoxic T cells. Science; 14 Oct 2021; DOI: 10.1126/science.abe9977

Cambridge researchers have discovered how T cells – an important component of our immune system – are able keep on killing as they hunt down and kill cancer cells, repeatedly reloading their toxic weapons.

spotlight on future therapeuticsCancerimmune systemGillian GriffithsWellcomeSchool of Clinical MedicineCambridge Institute for Medical Research (CIMR)T cells are trained assassins that are sent on their deadly missions by the immune system. There are billions of them in our blood, each engaged in a ferocious and unrelenting battle to keep us healthyGillian Griffiths T-cell assassins captured on film hunting down cancer cells and ‘reloading’ to kill again Killer T cell attacking a cancer cell


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YesNews type: NewsSuper Tags: Health and MedicineScience

Tree-dwelling mammals survived after asteroid strike destroyed forests

Latest Research in Cambridge - Thu, 14/10/2021 - 13:10

Overall, the study supports the hypothesis that the widespread destruction of forests following the asteroid’s impact favoured ground-dwelling mammals over their arboreal counterparts. However, it also provides strong evidence that some tree-dwelling animals also survived the cataclysm, possibly nesting in branches through the Cretaceous-Paleogene (K-Pg) extinction event.

“The recovery of terrestrial vertebrate life following the end-Cretaceous asteroid impact was one of the most important events in the history of life on Earth,” said senior author Dr Daniel Field, from Cambridge’s Department of Earth Sciences. “In this study, we drew on our previous work at Cambridge to investigate whether there were similarities in the ecological attributes of avian and mammalian survivors of the end-Cretaceous mass extinction.”

The K-Pg mass extinction event occurred when a meteor slammed into Earth at the end of the Cretaceous period. The impact and its aftereffects killed roughly 75% of the animal and plant species on the planet, including whole groups like the non-avian dinosaurs. 

For the study, the researchers analysed patterns of substrate preferences among all modern mammals and their ancestors, working backwards from the present day to before the K-Pg extinction event by tracing these traits along numerous phylogenetic trees — diagrams that illustrate the evolutionary relationships among species.

“Our study takes advantage of an ongoing revolution in our understanding of the tree of life, only made possible by researchers working in association with natural history collections,” said co-lead author Jacob Berv, from the University of Michigan. “By integrating data from such collections with modern statistical techniques, we can address new questions about major transitions in evolutionary history.”

The researchers classified each mammalian species as arboreal, non-arboreal, or semi-arboreal. To be considered arboreal, the species had to nearly always nest in trees. Categorising some species could be tricky. For example, many bat species spend a lot of time among trees but nest in caves, so bats were mostly categorised as non-arboreal or semi-arboreal.

“We were able to see that leading up to the K-Pg event, there was a spike in transitions from arboreal and semi-arboreal to non-arboreal habitat use across our models,” said co-lead author Jonathan Hughes, from Cornell University.

The work builds on a previous study led by Field, which used the same analytical method — known as ancestral state reconstruction — to show that all modern birds evolved from ground-dwelling ancestors after the asteroid strike.

“The fossil record of many vertebrate groups is sparse in the immediate aftermath of the extinction,” said Field, who is also curator of ornithology at the Cambridge Museum of Zoology. “Analytical approaches like ancestral state reconstruction allow us to establish hypotheses for how groups like birds and mammals made it through this cataclysm, which palaeontologists can then test when additional fossils are found.”

The analysis helps illuminate ecological selectivity of mammals across the K-Pg boundary despite the relatively sparse fossil record of mammalian skeletal elements from the periods immediately preceding and following the asteroid’s impact.

How the tree-dwelling ancestors of primates survived the asteroid’s destruction is unclear. According to the authors, it’s possible that some forest fragments survived the calamity or that early primates and their relatives were ecologically flexible enough to modify their substrate preferences in a world mostly denuded of trees.

Reference:
Jonathan J. Hughes et al. ‘Ecological selectivity and the evolution of mammalian substrate preference across the K–Pg boundary.’ Ecology and Evolution (2021). DOI: 10.1002/ece3.8114

Adapted from a Yale news release.

An asteroid strike 66 million years ago wiped out the non-avian dinosaurs and devastated the Earth’s forests, but tree-dwelling ancestors of primates may have survived it, according to a new study published in the journal Ecology and Evolution.

evolutionanimalprimateextinctionDinosaursDaniel FieldCornell UniversityYale UniversityDepartment of Earth SciencesSchool of the Physical SciencesMuseum of ZoologySchool of the Biological SciencesThe recovery of terrestrial vertebrate life following the end-Cretaceous asteroid impact was one of the most important events in the history of life on EarthDaniel FieldRod WaddingtonChimpanzee, Uganda


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Lockdown wellbeing: children who spent more time in nature fared best

Latest Research in Cambridge - Thu, 14/10/2021 - 06:01

A study has found that children who increased their connection to nature during the first COVID-19 lockdown were likely to have lower levels of behavioural and emotional problems, compared to those whose connection to nature stayed the same or decreased - regardless of their socio-economic status.

The study, by researchers at the University of Cambridge and the University of Sussex, also found that children from affluent families tended to have increased their connection to nature during the pandemic more than their less affluent peers. 

Nearly two thirds of parents reported a change in their child’s connection to nature during lockdown, while a third of children whose connection to nature decreased displayed increased problems of wellbeing - either through ‘acting out’ or by increased sadness or anxiety.

The results strengthen the case for nature as a low-cost method of mental health support for children, and suggest that more effort should be made to support children in connecting with nature - both at home and at school. 

The researchers’ suggestions for achieving this include: reducing the number of structured extracurricular activities for children to allow for more time outside, provision of gardening projects in schools, and funding for schools, particularly in disadvantaged areas, to implement nature-based learning programmes.

The study, published today in the journal People and Nature, also offers important guidance in relation to potential future restrictions during the COVID-19 pandemic.

“We know that access to and engagement with nature is associated with wide-ranging benefits in children and adults, including lowering levels of anxiety and depression, and reducing stress,” said Samantha Friedman, a researcher in the University of Cambridge’s Centre for Family Research, first author of the study.

She added: “The COVID-19 lockdowns meant that children no longer had their normal school activities, routines and social interactions. The removal of these barriers gave us a novel context to look at how changes in connection with nature affected mental health.
“Connecting with nature may have helped buffer some UK children against the effects of the lockdown, but we found that children from less affluent families were less likely to have increased their connection to nature during that time.”

An increased connection to nature was reflected in reports of children spending time gardening, playing in the garden or doing physical activities outdoors. This was commonly linked to having more time available for these activities during lockdown. Conversely, according to parents, a decreased connection to nature was explained by an inability to access some natural spaces due to travel restrictions in place at the time.

“Connecting to nature may be an effective way of supporting children’s wellbeing, particularly as children return to normal routines, such as school and extracurricular activities,” said Dr Elian Fink, a Lecturer in Psychology at the University of Sussex who was also involved in the study.

She added: “Our findings could be helpful in redesigning lockdown rules should the UK need to return to these conditions in the future, and particularly to countries whose lockdown restrictions prevented children from accessing nature at all. 
“Extending the amount of time that children can access nature, or extending the distance that children could be allowed to travel to access nature, could have a beneficial impact on their mental health.”

The study used an online survey to collect responses from 376 families in the UK, with children between three and seven years old, between April and July 2020. Over half of these families reported that their child’s connection to nature increased during the first COVID-19 lockdown. The remaining parents whose children’s connection to nature decreased or stayed the same during this period also reported that their children were experiencing greater wellbeing problems. 

A widely-used, gold standard questionnaire was used as a measure of each child’s mental health - assessing emotional problems such as unhappiness, worrying, anxiety and depression; and behavioural problems such as anger and hyperactivity.
“Mental health problems can manifest in different ways in different children. We found that a greater connection with nature was associated with reductions in both emotional and behavioural problems,” said Fink.

She added: “In reality the contrasting experiences of access to nature between different socio-economic groups may be even starker than our study found because respondents to our online study were largely drawn from more affluent societal groups.”
Parents with children between three and seven years old responded to the study survey with reference to one particular child. The researchers focused on this age group because they were likely to experience a lot of disruption due to the pandemic, and also have less understanding of what was happening. 

“Our study revealed the wide range of ways that parents can help children get more connected to nature. This might be a bit daunting to some, but it doesn’t have to be camping in the woods and foraging for food – it really can be as simple as going for a walk near your house or sitting outside for ten minutes a day,” said Friedman.

This research was funded by Newnham College, University of Cambridge.

Reference

Friedman, S. et al: ‘Understanding changes to children’s connection to nature during the Covid-19 pandemic and implications for child well-being.’ People and Nature, Oct 2021. DOI: 10.1002/pan3.10270

Children from less affluent backgrounds are likely to have found COVID-19 lockdowns more challenging to their mental health because they experienced a lower connection with nature than their wealthier peers, a new study suggests.

Samantha FriedmanClaire HughesUniversity of SussexCentre for Family ResearchSchool of the Biological SciencesChildren from less affluent families were less likely to have increased their connection to nature during lockdownSamantha FriedmanBen Wicks on UnsplashChildren outdoors in muddy wellies


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Vice-Chancellor’s Awards highlight research impact and engagement across Cambridge

Latest Research in Cambridge - Thu, 07/10/2021 - 15:44
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Photo by Universal Eye on Unsplash

Photo by Universal Eye on Unsplash

Academics from across the University have been recognised in this year’s Vice-Chancellor’s Research Impact and Engagement Awards for their research into improving management of maternity emergencies during COVID-19, helping rural communities in India become agriculturally more sustainable and aiding the Government’s real-time COVID-19 monitoring.

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The awards, now in their sixth year, are run by the University of Cambridge Public Engagement team and Research Strategy Office and are awarded in three categories: Early Career Researcher, Established Academic and the Collaboration Award. 

Early Career Researcher

The Early Career Researcher Award was awarded to Dr Jan van der Scheer, Research Associate at The Healthcare Improvement Studies (THIS) Institute and Hughes Hall. Scheer found a way to mobilise the ingenuity and expertise of NHS staff to adapt established processes for COVID scenarios.

Using THIS Institute’s Thiscovery platform, Scheer was able to bring together over 100 maternity unit staff, human factors specialists, and infection control experts to work to develop online methods for working collaboratively and at scale to build solutions together. 

The judges noted, Really rapid identification of the problem, consensus building and reflective practice with a wide range of practitioners resulting in shared learning, improved practice and better outcomes for patients. A really great example of how we should do healthcare research.”

Established Academic

The winner of the Established Academic Award was Daniela De Angelis from the University’s MRC Biostatistics Unit. 

De Angelis directs the Cambridge team of statisticians working on real time monitoring of the SARS-COV2 pandemic. This has provided the official Public Health England real time estimates and projections of the state of the pandemic in England, including: the R numbers; the risk of death after infection; the daily number of current and future infections and deaths; and the total number of currently infected individuals, by age group and England region.

These regular outputs are fed directly to the SAGE sub-group, Scientific Pandemic Influenza sub-group on modelling and have been key to the government’s management of the pandemic. The judges said, “Rapid response, building public trust and reflective practice, I was impressed with this project.”

Collaboration Award

The winners of the Collaborative Award was the TIGR2ESS team led by Professor Howard Griffiths, Professor of Plant Ecology in the Department of Plant Sciences and Fellow at Clare College. 

TIGR2ESS is a collaborative research programme led by the University of Cambridge, comprising more than 20 organisations and over 30 early career researchers who are working to find sustainable ways forward for Indian agriculture through engagement with rural communities, female empowerment, academic exchanges, and policy translation. 

Of the project, the judges said: “The impact of this project is truly epic in scale and importance. The project has had a huge influence on people and communities in the developing world. This was demonstrated through the exemplary, and very large scale of engagement that has been undertaken, working in close collaboration with partners.”

The awards were announced on 7th October by the University’s Public Engagement team in a live, interactive virtual ceremony on Twitter. 

Professor Stephen Toope, Vice-Chancellor of the University of Cambridge, said: 

“Each year, the Vice-Chancellor’s Awards are presented in recognition of outstanding achievement, innovation and creativity in impact and public engagement with research activities.

“We take pride in the outstanding research taking place across the University. Despite ongoing challenges, our academics have continued to undertake research with social, cultural and economic impact, locally and across the globe.”

The Vice-Chancellor’s Research Impact and Engagement Awards recognise outstanding achievement, innovation and creativity in devising and implementing ambitious engagement and impact plans which have the potential to create significant economic, social and cultural impact from, and engagement with, research. Each winner is offered a bursary to support their project.

This year’s winners and runners up are:

Established Academic Award

Winner: Daniela De Angelis (MRC Biostatistics Unit, School of Clinical Medicine) - Real-time monitoring of the SARS-COV2 pandemic

Runners up:

Fiona Mayne (Faculty of Education, School of Humanities and Social Sciences) - DIALLS: Dialogue and Argumentation for cultural Literacy Learning in Schools

Tony Kouzarides (Gurdon Institute, School of Biological Sciences) - Engagement with industry to convert discoveries into therapies

Alessandro Launaro (Faculty of Classics, School of Arts and Humanities) - Past forward – Archaeological research as a driver of local growth

Early Career Researcher Award

Winner: Jan van der Sheer (The Healthcare Improvement Studies (THIS) Institute, Department of Public Health and Primary Care, School of Clinical Medicine) - Building solutions together: improving management of maternity emergencies during COVID-19

Runners up: Kate Noble (The Fitzwilliam Museum, School of Arts and Humanities) - ‘It’s Our Museum Too’: Exploring cultural value in collaboration with a local community group

Ewan St. John Smith (Department of Pharmacology, School of Biological Sciences) - Explaining pain

Ebele Mogo (MRC Epidemiology Unit, School of Clinical Medicine) - Engage Africa Foundation

Collaboration Award

Winner: TIGR2ESS (Transforming India’s Green Revolution by Research and Empowerment for Sustainable food Supplies): UK-India Collaboration is Driving High-level Policy Engagement and Positive Outcomes for Rural Communities in India. Lead researcher: Professor Howard Griffiths (Department of Plant Sciences, School of Biological Sciences)

Runners up: Rapid application of industrial engineering and operations management research to hospitals to address multiple COVID challenges. Lead Researcher: Professor Duncan McFarlane (Institute for Manufacturing, School of Technology)

Digital Security by Design: Transitioning CHERI capability-based security through the Arm Morello industrial demonstrator. Lead researcher: Professor Robert N. M. Watson (Department of Computer Science and Technology, School of Technology)

Understanding and reducing the impact of COVID-19 on ethnic minorities in the UK. Lead researcher: Dr Raghib Ali (MRC Epidemiology Unit, School of Clinical Medicine) 

TopBuilt with Shorthand Summary: 

Academics from across the University have been recognised in this year’s Vice-Chancellor’s Research Impact and Engagement Awards for their research into improving management of maternity emergencies during COVID-19, helping rural communities in India become agriculturally more sustainable and aiding the Government’s real-time COVID-19 monitoring.

Image: Affiliation (schools and institutions): The Healthcare Improvement Studies InstituteDepartment of Public Health and Primary CareSchool of Clinical MedicineMedical Research Council (MRC) Biostatistics UnitDepartment of Plant SciencesSchool of the Biological SciencesPeople (our academics and staff): Jan van der ScheerDaniela De AngelisHoward GriffithsStephen ToopeSection: ResearchNews type: NewsSuper Tags: Health and MedicineScienceTechnologyUniversity News

A mental health revolution

Latest Research in Cambridge - Thu, 07/10/2021 - 15:36
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.text-edit-colour-swatch.Theme-ForegroundColor-16,.text-edit-dropdown-colour.Theme-BackgroundColor-16,.text-edit-dropdown-colour.Theme-ForegroundColor-16{background:#c5dfb4}.Theme-BackgroundColor-16{background-color:#c5dfb4}.Theme-BackgroundColor-17{background-color:transparent}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-17,.text-edit-dropdown-colour.Theme-BackgroundColor-17{background:0 0} /*-->*/ " + "ipt>"); } })(navigator, 'userAgent', 'appVersion', 'script', document); //--> TwitterFacebook A mental health revolution

Cambridge-led computerised cognitive assessments transform early detection and treatment of neurological and psychiatric disorders.

Impact at a glance
  • The ‘Cambridge Neuropsychological Test Automated Battery’ (CANTAB) was invented to bridge a translational gap between basic neuroscience and classical neuropsychological assessment.
  • Since August 2013, over 1,100 publications have used CANTAB.
  • Since August 2013, CANTAB and related developments have been used in over 33,800 cognitive assessments and 261 clinical trials.
  • CANTAB is available in almost 50 languages and has been used in over 100 countries.
  • CANTAB has improved patient management and contributed to drug development.
“Our dementia diagnosis rate has improved from 39% to over 46%. CANTAB Mobile has raised awareness of mild cognitive impairment in primary care and acted as a stimulus to actively encourage practices to assess patients at an early stage.”A Dementia Programme manager from a Clinical Commissioning Group (CCG)

“When it comes to cognitive impairments and psychiatric disorders, early detection, and early treatment are key, similar to physical health,” says Barbara Sahakian, Professor of Clinical Neuropsychology in the University’s Department of Psychiatry.

Over thirty years ago, Sahakian co-invented a group of cognitive assessments called the Cambridge Neuropsychological Test Automated Battery (CANTAB), which have gone on to revolutionise clinicians’ ability to diagnose and treat patients, in addition to playing an invaluable role in research and the development of new drugs.

A computerised revolution

The story of CANTAB began in the late 80’s when Sahakian was working in one of the UK’s first clinics for the early detection of Alzheimer’s disease. She explains that there were simply no good assessment tools available, so she decided to create one. She collaborated with her husband Trevor Robbins, Professor of Cognitive Neuroscience in the University’s Department of Psychology, to configure a set of computerised tests that took advantage of a new technology that had just become available in 1987: the touch sensitive screen.

“Although these touch screens were nothing like the ones we use in our everyday life today,” laughs Sahakian, recalling how awkward it was to attach a separate bulky touch sensitive screen to the computer.

The computerised nature of CANTAB was revolutionary. Unlike the pen and paper language-based cognitive assessments, which had long been the standard way of measuring brain functioning, CANTAB was more objective, precise and accessible. The touch-screen technology and the non-verbal nature of the tests reduced the need for the user to have a certain IQ or language skill level. The tests were also less susceptible to experimental bias or human error.

Later the invention of the iPad meant that specialised equipment and a trained professional to administer the tests were no longer required – the minimal instructions were incorporated into the test. Sahakian and Robbins assisted in the development of CANTAB Mobile for use in general practitioner clinics making cognitive testing increasingly accessible and cost effective.

Impacting lives

The sensitivity of CANTAB means it’s perfectly suited to clinical trials assessing the effectiveness of new drugs. Its ability to be used across languages, cultures and ages adds a richness to datasets, which has huge implications for the progression of international research into cognitive impairments and psychiatric and neurological disorders.

Since August 2013, CANTAB and related tests have been used in over 33,800 cognitive assessments and 261 clinical trials, in over 100 countries. CANTAB has been used in studies of therapeutic agents, for example in depression, attention deficit hyperactivity disorder (ADHD) and Parkinson’s disease.

“We’re thrilled CANTAB has had such an impact on people’s lives,” says Sahakian. “We’ve always wanted our research to not only elucidate the neural mechanisms underlying behaviour and cognition but also to have a strong application for individuals, society, and psychological and neurological disorders.

“We wanted CANTAB to be the Gold Standard in the field – I think we’ve achieved that.”

How does CANTAB work? CANTAB has been validated using patient studies and neuroimaging studies in healthy volunteers and refined over a period of 30 years. It measures specific brain functions across a range of disorders and syndromes.

Whereas many other traditional tests may assess a behavioural outcome, CANTAB correlates with neural networks meaning that it measures the functioning of a specific area of the brain in a similar way to a neuroimaging scan. For example, tests may measure decision making and high-level thinking, which are examples of executive-functioning, in order to provide an indication of the functioning of the prefrontal cortex. An answer to Alzheimer’s disease?

“We often think about the importance of physical health and keeping fit and active, but we rarely think about this in the context of our brains,” says Sahakian.

Sahakian has long advocated for an awareness of the ‘fitness’ of our brains and testing early to identify if our brains are functioning in the way they should do. This could not be more crucial than with Alzheimer’s disease, the most common cause of dementia in the UK.

The cause of this progressive neurological disorder is not fully understood, and a cure has yet to be identified. However, treatments for the cognitive symptoms of Alzheimer’s disease, approved by the National Institute for Health and Care Excellence (NICE), are available, and recently the Food and Drug Administration (FDA) approved a treatment for the underlying disease process. It’s critical that these drugs are administered as early as possible, which is why early detection is crucial.

CANTAB PAL

The sensitivity of the Paired Learning Associate Test (PAL), which forms part of CANTAB, was found to predict probable Alzheimer’s disease 32 months before formal diagnosis in patients with subjective memory complaints. “This is really important because you have to treat the disease at the earliest possible point to have an impact on patients’ quality of life,” says Sahakian.

The commercialisation of CANTAB via the spin out Cambridge Cognition meant that CANTAB PAL could be used in clinics up and down the country and across the world. Excitingly, PAL has been used in a number of clinical trials in the development of new drugs for dementia.

“My journey with CANTAB began with a deep desire to secure a better quality of life and a longer life for those suffering from Alzheimer’s disease,” said Sahakian. “It’s been incredible to see the development of new drugs which could dramatically improve outcomes for patients. We still have a long way to go, but CANTAB means we have the tools we need to get there.”

Tackling gambling disorders

Sahakian holds up a photograph of former Arsenal and England player Paul Merson, it reads ‘thank you for everything.’ The photo shows a young Merson in his Arsenal strip, storming up the pitch in celebration of a goal. The snapshot captures a moment of pure jubilation but hides the reality of the battles he faced. Merson has struggled with addictions throughout his adult life. Of these addictions he says his gambling disorder was the worst.

 'To Barbara, thank you for everything, love Paul Merson x'

 'To Barbara, thank you for everything, love Paul Merson x'

Sahakian met Merson as part of the upcoming documentary, Paul Merson: Football, Gambling and Me. She explains that disordered gambling is a growing problem, and it’s increasingly occurring in the younger population, which is likely due to betting being available online and betting adverts airing alongside sports matches.

“It begins impulsively,” explains Sahakian “maybe an individual sees their dad going into a betting shop or they see an advert on TV that says: “bet now before the game starts”. At first, they bet just for a bit of fun or to have a heightened experience. They might get a win or a close miss which reinforces false beliefs that they’re going to be lucky. And so, they bet more and more until it becomes habitual. They may also need to escalate bets to get the same dopamine rush.”

CANTAB Cambridge Gambling task

Sahakian, along with others, developed the CANTAB Cambridge Gambling task which was administered to Merson as part of the documentary. The task involves a betting game which assesses risk taking and decision-making behaviour.

“What we find is that pathological gamblers are more likely to place higher bets and to ground out, they also don’t make adjustments based on perceived levels of risk.”

Hot and cold cognition

Sahakian describes these behaviours as examples of ‘hot cognition’ which refers to decisions which are emotion-led as opposed to rational or ‘cold cognition’ decisions. Interestingly, there are advantages to both types of decision making as Sahakian found in her study, published in Nature, investigating entrepreneurs.

“Entrepreneurs are risky decision makers, but unlike pathological gamblers, they also have very good cognitive flexibility and cold planning. Therefore, they are able to take big risks, but if something isn’t working, they are able to switch and try a different way to be successful.”

It’s the interaction between hot and cold cognition which those with problem gambling may struggle with. Cognitive behavioural treatments may involve waiting and not betting immediately when you have the urge to gamble. This time delay can ‘cool down’ hot thinking and bring a more rational perspective.

The CANTAB Cambridge Gambling task can be used by clinicians to assess how excessive the problem behaviours are. As treatment is started and continued it can be used to check on the progress of the patient and their recovery.

To date, the task has been used in nearly 200 publications. “It’s wonderful to see that the Cambridge Gambling task has been instrumental in advancing research in the area of addictive behaviours and dependencies,” says Sahakian. “The more we understand about these disorders the greater the chance we have of developing effective treatments.”

Watch Paul Merson: Football, Gambling and Me at 9pm, 11 October, BBC1.

TopBuilt with Shorthand Summary: 

Cambridge-led computerised cognitive assessments transform early detection and treatment of neurological and psychiatric disorders.

Image: Affiliation (schools and institutions): Department of PsychiatryDepartment of PsychologySchool of Clinical MedicineSchool of Biological SciencesPeople (our academics and staff): Barbara SahakianTrevor RobbinsSubject (including Spotlight on ... where applicable): StoriesSection: ResearchNews type: NewsSuper Tags: Health and Medicine

Crayfish and carp among the invasive species pushing lakes towards ecosystem collapse

Latest Research in Cambridge - Thu, 07/10/2021 - 00:01

Human activity and climate change are causing invasive non-native species to spread rapidly across the globe. Researchers have found that certain invasive species can push lake ecosystems beyond a critical ‘tipping point’, causing a sudden shift from healthy to degraded conditions that is difficult to reverse. 

Invasive fish such as Asian silver carp Hypophthalmichthys molitrix, and crustaceans such as American signal crayfish Pacifastacus leniusculus, were found to significantly reduce the abundance of other important organisms in lakes and degrade water quality. The findings, published today in the journal Global Change Biology, also provide guidance on the best ways to manage waterbodies.

Shallow lakes naturally exist in one of two alternative stable states: either healthy - with clear water with an abundance of vegetation, or degraded - with cloudy water dominated by algae. When a lake is in the latter state, algae use up all the nutrients in the water and block sunlight, preventing the growth of aquatic vegetation that would aid ecosystem recovery. 

Deteriorated, algae-dominated freshwater ecosystems also threaten the health and water security of human populations. Blooms of cyanobacteria, known as ‘blue-green algae’ can produce toxins that contaminate food webs and poison water supplies.

“Algal blooms represent one of the most significant threats to the security of the Earth’s surface freshwaters. Simply undoing the circumstances that triggered a tipping point will not restore the ecosystem - the road to recovery is slow and steep,” said Dr Sam Reynolds in the University of Cambridge’s Department of Zoology, first author of the report. 

However, although invasive species are recognised as a significant threat to global biodiversity, their impacts on ecosystem services may not be uniformly negative. Invasive molluscs, including the zebra mussel Dreissena polymorpha, were found to engineer the opposite biological and environmental response: they delay ecosystem collapse and potentially aid the recovery of degraded lake ecosystems.  

“Managers of drinking water reservoirs, for example, may be able to avoid the cost of dealing with blooms of harmful algae, by removing invasive crayfish but allowing established non-native zebra mussels to remain and act as biological filters,” said Professor David Aldridge, senior author of the report. 

He added: “Early detection and rapid response plans should always be our first line of attack. But in situations where invaders have already established and can no longer be eradicated, it may be appropriate to embrace their positive effects.”

The researchers focused on shallow lake ecosystems, but say that their framework could be applied to other critical ecosystems that experience catastrophic tipping points - such as coral reefs, kelp forests and desert shrublands.

This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

Reference
Reynolds, S. A. & Aldridge, D. C.: 'Global impacts of invasive species on the tipping points of shallow lakes'. Global Change Biology, October 2021. DOI 10.1111/gcb.15893

Certain invasive, non-native species can disrupt lakes to the point of rapid ecosystem collapse, contaminating water for drinking, aquaculture and recreation, a new study has found.

Sustainable EarthSam ReynoldsDavid AldridgeDepartment of ZoologySchool of the Biological SciencesSimply undoing the circumstances that triggered a tipping point will not restore the ecosystem - the road to recovery is slow and steep.Sam ReynoldsMark Philpott on FlickrAmerican signal crayfish


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Variant hunters: the story behind the race to sequence COVID-19 genetics

Latest Research in Cambridge - Mon, 04/10/2021 - 13:50

Hear from some of the scientists behind the UK’s nationwide sequencing effort to track SARS-CoV-2. Sir Patrick Vallance (the government’s Chief Scientific Adviser) also describes how the expertise that came together during the pandemic is now recognised across the world – and why it’s crucially important to continue to sequence to be ready for future pandemics.

This pioneering work is being carried out by the COVID-19 Genomics UK (COG-UK) consortium, which comprises numerous academic institutions, four public health agencies and the Wellcome Sanger Institute, and is administered by the University of Cambridge. “Incredibly impressive, incredibly high quality and incredibly focused on the mission to make sure that as many people benefited from the science as possible,” Sir Patrick Vallance.

The variant hunters are helping us to understand how and why the COVID-19 virus is spreading, allowing us to fight back against the COVID-19 pandemic.

COVID-19GenomicsSharon PeacockPatrick VallanceWellcome Sanger InstituteDepartment of MedicineSchool of Clinical Medicine The Variant Hunters


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Encourage wealthy and well-connected to use their influence to tackle climate change

Latest Research in Cambridge - Thu, 30/09/2021 - 16:00

In their roles as consumers, investors, role models, organisational participants, and citizens, people in this group can help shape the choices available to themselves and others, providing options that either exacerbate or mitigate climate change.

Most research into how we can reduce our climate impact has focused on changing the consumer behaviour of the masses - recycling and switching off lights at home, for example. The authors say that the focus must shift to finding ways of motivating people of high socioeconomic status to change many kinds of behaviours, because what they do can have a much greater impact on carbon emissions. 

The study defines high socioeconomic status as a person’s position in the structure of society, including not only their wealth and income, but also their ‘social resources’, which include social class, occupation, and social network. It encompasses a much broader spectrum of people than just the super-rich, including everyone with an annual income of US $109,000 and above.

“High socioeconomic status people aren’t just those with more money, but those with better social networks. Their connections can enable them to influence behaviours and policies to help mitigate climate change – and we need to find ways to encourage them to do this,” said Dr Kristian Nielsen, a postdoctoral researcher in the University of Cambridge’s Department of Psychology, first author of the paper.

He added: “By saying it’s only the super-rich that need to change their behaviour, we ignore the power that others have to help tackle climate change though their influence.”

The climate impact of air travel is now well known, but over 50% of greenhouse gas emissions from flying are caused by just 1% of the world’s population. The study highlights the need to change social norms associated with frequent flying - usually by people of high socio-economic status - but also to look beyond their role as consumers. 

“People of higher socioeconomic status could also act as role models, making more climate-friendly choices that influence others – for example driving electric cars or eating a vegan diet. You don’t need a massive income to be a role model, you just need to be well-connected,” said Nielsen. 

Investments also provide an opportunity for those of higher socioeconomic status to mitigate climate change. Although attention has focused on shifting the investment of large pension funds away from fossil fuel companies, the researchers say that the investment portfolios of individuals - particularly those with immense wealth - can also have a very significant influence. 

In addition, high socioeconomic status individuals - whether owners or employees - can help to mitigate climate change through their organisations, for example by changing suppliers, business culture and investments.  

And as citizens, people of high socioeconomic status have the networks to help them organise social movements, and better access politicians and decision-makers. Their financial resources also help: making donations helps smooth the path to advancing social change. 

“Our study focused on people of high socioeconomic status because they have generated many of the problems of fossil fuel dependence and associated climate change, which affect the rest of humanity. And they are also well positioned to do something about it,” said Nielsen.

He added: “When certain people change their behaviour for the good of the climate it can have spill-over effects that go way beyond the effects of the average person, and lead to systemic change.” 

This research was funded by the Carlsberg Foundation. 

Reference
Nielsen, K.S. et al: ‘High socioeconomic status people are key to locking in or rapidly reducing energy-driven greenhouse gas emissions.’ Nature Energy, Sept 2021. DOI: 10.1038/s41560-021-00900-y

 

A paper published today in the journal Nature Energy identifies five ways that people of high socioeconomic status have a disproportionate impact on global greenhouse gas emissions - and therefore an outsized responsibility to facilitate progress in climate change mitigation.

Climate changeKristian NielsenDepartment of PsychologySchool of the Biological SciencesBy saying it’s only the super-rich that need to change their behaviour, we ignore the power that others have to help tackle climate change though their influence.Kristian NielsenNiek Verlaan on PixabayMan in suit on mobile phone


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Rate of mental disorders among children remained stable in 2021 after previous rise

Latest Research in Cambridge - Thu, 30/09/2021 - 15:57

The report, Mental Health of Children and Young People in England 2021, showed that among six to 16 year olds, the proportion with a probable mental disorder remained at one in six (17%) in 2021. Among 17 to 19 year olds, the rate was also one in six (17%).

Figures were statistically similar in 2020 and 2021. In 2020, the rate of probable mental disorders was also one in six for both these age groups.

Both years showed an increase from 2017, when one in nine (12%) six to 16 year olds and one in ten (10%) 17 to 19 year olds had a probable mental disorder.

This report looks at the mental health of children and young people in England in 2021 and how this has changed since 2017 and 2020. Views on family life, education and services and experiences during the coronavirus (COVID-19) pandemic have also been collected. The findings draw on a sample of 3,667 children and young people aged between six and 23 years old, who were surveyed in 2017 and 2021.

The survey was carried out earlier this year by the Office for National Statistics, the National Centre for Social Research, University of Cambridge and University of Exeter.

Professor Tamsin Ford, Head of Psychiatry at the University of Cambridge and one of the study authors, said: “We can be reassured that the mental health of children and young people has not deteriorated further, but this survey suggests there has been no improvement. We need to work hard to prevent further deterioration and to ensure that those who need it have access to effective support.”

This publication reports individual level change in mental health over time for the same group of children and young people. Some change may be due to different rates of mental health conditions being present at different ages. It shows 39% of children now aged six to 16 experienced a deterioration in their mental health between 2017 and 2021, while 22% saw an improvement.

Among young people now aged 17 to 23, 53% experienced a decline in mental health since 2017 and 15% experienced an improvement over that time. 

Girls now aged between 11 and 16 were more likely to have experienced a decline in mental health (43%) than boys the same age (34%). This trend was also seen among those now aged 17 to 23, where young women were more likely to have experienced deterioration (61%) than young men (44%).

Other topics covered in the report included eating and sleeping problems, loneliness, social media usage and household circumstances.

Adapted from a press release by NHS Digital.

A survey published today by NHS Digital found one in six children in England had a probable mental disorder in 2021 – a similar rate to 2020 but an increase from one in nine in 2017.

Mental healthNeuroscienceCoronavirusCOVID-19Tamsin FordNHS DigitalSchool of Clinical MedicineDepartment of PsychiatryWe need to work hard to prevent further deterioration and to ensure that those who need it have access to effective supportTamsin FordNicolò CanuTeenager


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Fewer than one in 20 people living with HIV in England expected to be unaware of status by 2025

Latest Research in Cambridge - Fri, 24/09/2021 - 08:49

In 2014, UNAIDS set an ambitious target of 90-90-90 by 2020 – that is, 90% of all people living with HIV will know their HIV status; 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy; and 90% of all people receiving antiretroviral therapy will have viral suppression. 

According to the Cambridge and PHE team, in 2019 there were an estimated 105,200 people living with HIV in the UK, of whom 94% were aware of their HIV status. In addition, 98% of those living with diagnosed HIV were on treatment, and 97% of these were virally suppressed. In other words, England had already reached the UNAIDS goals.

In a publication today in The Lancet Public Health, the researchers extended their analysis of evidence from multiple surveillance, demographic, and survey datasets relevant to HIV in England from estimating HIV prevalence in a single year to estimating the trends over time in HIV prevalence. Trends in the number of people living with HIV, the proportion of people unaware of their HIV infection, and the corresponding prevalence of undiagnosed HIV are reported.

According to their analysis, the estimated number of people in England living with HIV aged 15-74 years who were unaware of their infection halved from 11,600 in 2013 to 5,900 in 2019, with a corresponding fall in prevalence from 0.29 to 0.14 per 1,000 people.

At the same time, the increase in the number of people living with diagnosed HIV resulted in the total number of people living with HIV rising from 83,500 to 92,800 over the same period. The percentage of people living with HIV whose infection was diagnosed therefore steadily increased from 86% in 2013 to 94% in 2019, reaching the UNAIDS target in 2016 – and even earlier, in 2013, for Black African heterosexuals.

Professor Daniela De Angelis from the MRC Biostatistics Unit, the study’s senior author, said: “Overall, we see a positive picture for the HIV epidemic in England, with a dramatic fall in the number of people living with undiagnosed HIV. We estimate we are already several years ahead of the UNAIDS 2020 goals and are on target to reach 95% diagnosed by 2025 and to eliminate HIV infections by 2030.

Dr Anne Presanis from the MRC Biostatistics Unit added: “Examined more closely, the situation is not as positive for everyone. We estimate that areas of England outside London have not seen as steep a decrease in undiagnosed HIV prevalence as in London, and there is evidence of missed opportunities to diagnose HIV infections among some population subgroups.”

In England, gay, bisexual, and other men who have sex with men, and Black African heterosexuals remain disproportionately affected by HIV, with considerably higher undiagnosed HIV prevalence per population in 2019 than heterosexuals in other ethnic groups. However, undiagnosed HIV prevalence rates within these communities have seen dramatic falls: for gay, bisexual, and other men who have sex with men, prevalence fell from 13.9 to 5.4 per 1,000, and for Black African heterosexuals prevalence fell from 3.3 to 1.7 per 1,000 population.

London saw more dramatic falls in the prevalence of undiagnosed HIV during the study period than other regions of England, down from 0.74 to 0.31 per 1,000, compared to a decrease from 0.20 to 0.11 per 1,000 outside London.

Although sexual health clinics provide free and confidential HIV testing to all clinic attendees, the researchers estimated that among heterosexuals in an ethnic group other than Black African, undiagnosed prevalence in clinic attendees in 2019 was more than 30 times greater than in those who had not attended in the past year. This implies that sexual health clinics are missing opportunities for testing attendees. This is in line with findings from Public Health England that among individuals outside those subgroups at greatest risk of HIV infection, the proportion declining a HIV test had increased to more than one in four (27%) in 2016.

The researchers say their estimates have important implications for efforts to eliminate HIV transmission in England and the UK.

Dr Valerie Delpech, head of the HIV Team at Public Health England said: “This research is good news and shows that combination prevention, and in particular HIV testing and early treatment, is working in England. The increasing use of pre-exposure prophylaxis among persons at higher risk of HIV has further amplified our response to end HIV transmission. Nevertheless, further reducing the number of people who remain undiagnosed with HIV infection will become very challenging in the coming years. This is particularly the case for heterosexuals who may not consider themselves at risk of HIV.

“The priority must be to ensure that all sexual health clinic attendees are offered and encouraged to accept a HIV test, regardless of ethnicity, rather than the 73% that currently do test. If we can increase the number of clinic attendees unaware of their HIV status who get tested and diagnosed, as well as improve partner notification, the prospect of eliminating HIV transmission becomes increasingly likely.”

The research was funded by the Medical Research Council and Public Health England.

Reference
Presanis AM, et al. Trends in undiagnosed HIV prevalence in England and implications for eliminating HIV transmission by 2030: an evidence synthesis model. Lancet Public Health; 23 Sept 2021; DOI: 10.1016/S2468-2667(21)0042-0

England is on track to have diagnosed 95% of people living with HIV by 2025, putting it in a strong position to eliminate HIV transmission by 2030, say researchers at the MRC Biostatistics Unit, University of Cambridge, and Public Health England (PHE).

HIV/AIDSPublic healthInfectious diseasesAnne PresanisDaniela De AngelisMedical Research CouncilPublic Health EnglandSchool of Clinical MedicineCambridge Public HealthCambridge Infectious DiseasesMedical Research Council (MRC) Biostatistics UnitOverall, we see a positive picture for the HIV epidemic in England, with a dramatic fall in the number of people living with undiagnosed HIVDaniela De AngelisAndy McCarthyRed ribbon


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PhD Studentship : Elucidating DNA damage repair mechanisms

Applications are invited for a 4-year Cancer Research UK funded PhD Studentship in the research group of Professor Steve Jackson at the Gurdon Institute, University of Cambridge, https://www.stevejacksonlab.org/.

DNA in our cells is frequently subject to a wide array of molecularly distinct forms of damage. To cope with this, life has evolved multiple DNA repair and associated processes, collectively termed the DNA-damage response (DDR). While considerable progress has been made in identifying DDR components and their regulators, much remains to be learned about how they operate and are controlled.

Over the past few years, members of the Steve Jackson laboratory (including several past and existing graduate students) have successfully implemented state-of-the art CRISPR/Cas9 gene-editing and CRISPR/Cas9 genetic screens to identify and characterize novel DNA repair proteins and regulators, including those imparting sensitivity or resistance to anti-cancer drugs (e.g., Balmus et al., Nat Commun. 2019 Jan 8;10(1):87 and Dev et al., Nat Cell Biol. 2018 Aug;20(8):954-965). This PhD project will build on this and other expertise in the host laboratory to discover new functional interactions and networks in DNA repair and associated DNA-damage responses (DDR), and where possible translate this knowledge towards expanding our understanding of drug sensitivity and resistance in cancer therapy.

Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second-class degree (or equivalent) in a biological discipline that is relevant to the project. Applicants with relevant research experience, gained through Master's study or while working in a laboratory are strongly encouraged to apply. Ideally, the candidate will have a strong background in molecular and cellular biology. Motivation, creativity and intellectual independence are desirable, as are excellent communication skills with the ability to work collaboratively.

This project is funded by a Cancer Research UK studentship and will commence in October 2022 and provides a maintenance grant and tuition fees at the UK rate. Non-UK applicants will be considered only if they are able to fund the overseas fees differential or if they are awarded a suitable scholarship.

To apply, please email a cover letter, CV, academic transcripts, and contact details for at least two academic referees to: Dr Kate Dry (Information Specialist, Jackson lab), k.dry@gurdon.cam.ac.uk.

Please quote reference PR28165 on your application and in any correspondence about this vacancy. The studentship will be administered through the Department of Biochemistry, Prof Jackson's departmental affiliation. For further information about the course go to: https://www.bioc.cam.ac.uk/postgraduates.

The closing date for applications is 21st November 2021, with interviews expected to take place shortly after this date.

For informal queries regarding the post please contact Prof Steve Jackson via his Information Specialist, Dr Kate Dry (k.dry@gurdon.cam.ac.uk).

Please quote reference PR28165 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Rates of infectious disease linked to authoritarian attitudes and governance

Latest Research in Cambridge - Tue, 21/09/2021 - 11:07

According to psychologists, in addition to our physiological immune system we also have a behavioural one: an unconscious code of conduct that helps us stay disease-free, including a fear and avoidance of unfamiliar – and so possibly infected – people.

When infection risk is high, this “parasite stress” behavior increases, potentially manifesting as attitudes and even voting patterns that champion conformity and reject “foreign outgroups” – core traits of authoritarian politics.

A new study, the largest yet to investigate links between pathogen prevalence and ideology, reveals a strong connection between infection rates and strains of authoritarianism in public attitudes, political leadership and lawmaking.

While data used for the study predates COVID-19, University of Cambridge psychologists say that greater public desire for “conformity and obedience” as a result of the pandemic could ultimately see liberal politics suffer at the ballot box. The findings are published in the Journal of Social and Political Psychology.

Researchers used infectious disease data from the United States in the 1990s and 2000s and responses to a psychological survey taken by over 206,000 people in the US during 2017 and 2018. They found that the more infectious US cities and states went on to have more authoritarian-leaning citizens.

The US findings were replicated at an international level using survey data from over 51,000 people across 47 different countries, comparing responses with national-level disease rates.        

The most authoritarian US states had rates of infectious diseases – from HIV to measles – around four times higher than the least authoritarian states, while for the most authoritarian nations it was three times higher than the least.

This was after scientists accounted for a range of other socioeconomic factors that influence ideology, including religious beliefs and inequalities in wealth and education. They also found that higher regional infection rates in the US corresponded to more votes for Donald Trump in the 2016 US Presidential Election.     

Moreover, in both nations and US states, higher rates of infectious disease correlated with more “vertical” laws – those that disproportionately affect certain groups, such as abortion control or extreme penalties for certain crimes. This was not the case with “horizontal” laws that affect everyone equally.

“We find a consistent relationship between prevalence of infectious diseases and a psychological preference for conformity and hierarchical power structures – pillars of authoritarian politics,” said study lead author Dr Leor Zmigrod, an expert in the psychology of ideology from the University of Cambridge.

“Higher rates of infectious diseases predicted political attitudes and outcomes such as conservative voting and authoritarian legal structures. Across multiple geographical and historical levels of analysis we see this relationship emerge again and again.”

“We found that pathogen rates from over twenty years ago were still relevant to political attitudes as recently as 2016. If COVID-19 increases the allure of authoritarian politics, the effects could be long-lasting,” said Zmigrod, from Cambridge’s Department of Psychology.

The study also tested whether the link to authoritarianism held for zoonotic diseases – those only acquired from animals – but found it related solely to human-to-human disease transmission, further suggesting this is part of a “behavioural immune system” say researchers.   

In 2017, Cambridge psychologists worked with TIME Magazine to launch a two-part personality survey. Part one was based on the Harry Potter novels, but participants could also opt in to a second part used for scientific research, which included a textbook measure of authoritarianism.

Participants were presented with pairs of personality traits and asked which quality was most important for a child to possess e.g. independent or respectful, obedient or self-reliant. Over a quarter of a million people completed this section and provided their postal – or zip – codes.

For disease levels in US states, scientists used data from the Centers for Disease Control and Prevention (CDC) from between 1993 and 2007. These included rates of pathogens such as viral hepatitis, herpes, HIV, measles and chicken pox.

For US cities, the Cambridge team calculated rates of chlamydia and gonorrhea from 2002 to 2010. For the 47 nations, an index of nine infectious diseases ranging from tuberculosis to malaria was used.

“These findings are a warning sign that disease-avoiding behaviors have profound implications for politics,” added Zmigrod. “COVID-19 might shape people’s tendencies towards conformity and obedience, and this could be converted into authoritarian political preferences, voting patterns, and laws.”

“Health and politics may be more intertwined than we previously envisioned.”

Researchers argue that a desire for “conformity and obedience” as a result of COVID-19 could boost authoritarianism in the wake of the pandemic.

politicsCOVID-19Infectious diseasessocial psychologyLeor ZmigrodSchool of the Biological SciencesDepartment of PsychologyIf COVID-19 increases the allure of authoritarian politics, the effects could be long-lastingLeor ZmigrodMaria Thalassinou via UnsplashA protester holds a sign comparing President Trump to Italian dictator Benito Mussolini.


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Autistic individuals are more likely to be LGBTQ+

Latest Research in Cambridge - Mon, 20/09/2021 - 15:32

The findings have important implications for the healthcare and support of autistic individuals. The results are published in the journal Autism Research.  

For many years it was wrongly assumed that autistic individuals are uninterested in sexual or romantic relationships, but this is not the case. In recent years, small studies have suggested that autistic individuals are more likely to experience a wider diversity of sexual orientations and are less likely to have sexually transmitted infections (STIs). However, the existing evidence has been limited in size and scope.

In the largest study to date on these topics, the team at the Autism Research Centre used an anonymous, self-report survey to study the sexual activity, sexual orientation, and sexual health of autistic adults. Overall, 1,183 autistic and 1,203 non-autistic adolescents and adults (aged 16-90 years) provided information about their sexual activity, sexual orientation, and medical history of STIs.

The results showed that the majority of autistic adults (70% of autistic males and 76% of autistic females) engage in sexual activity—although they do so to a lesser degree than their non-autistic peers (89% of both non-autistic males and females report engaging in sexual activity). In contrast to previous findings, the results also found that there were no differences in likelihood of ever contracting an STI, or the age at which participants first engaged in sexual activity, between autistic and non-autistic individuals.

In addition, the study found that autistic adults and adolescents are approximately eight times more likely to identify as asexual and ‘other’ sexuality than their non-autistic peers. And there were sex differences in sexual orientation: autistic males are 3.5 times more likely to identify as bisexual than non-autistic males, whereas autistic females are three times more likely to identify as homosexual than autistic females.

When comparing autistic females and males directly, autistic females were more likely to be sexually active; more likely to identify as asexual, bisexual, and ‘other’ sexuality; and were less likely to identify as heterosexual.

Elizabeth Weir, a PhD candidate at the Autism Research Centre in Cambridge, and the lead researcher of the study, said: “Understanding the intersectional identities of autistic individuals who are asexual, bisexual, homosexual, or ‘other’ sexuality is key. It is particularly important that healthcare providers and educators use language that is affirming and accepting of all sexual orientations and gender identities when providing sexual education and sexual health screening checks to autistic and non-autistic people alike.” 

Dr Carrie Allison, Director of Strategy at the Autism Research Centre and a member of the team, said: “We must ensure that autistic individuals are receiving equal access to healthcare and support in their choices in their personal lives, to enjoy fulfilling lives and good mental health.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “This new study is an important example of applied health research with policy relevance for health and social care services.”

Reference
Weir, E., Allison, C., & Baron-Cohen, S. The sexual health, orientation, and activity of autistic adolescents and adults. Autism Research (2021). DOI: 10.1002/aur.2604

 

New research from the University of Cambridge suggests that autistic individuals are less likely to identify as heterosexual and more likely to identify with a diverse range of sexual orientations than non-autistic individuals.

autismsexualityLGBTSimon Baron-CohenCarrie AllisonElizabeth WeirAutism Research CentreSchool of Clinical Medicine Cecilie Johnsen via UnsplashPride flag


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SCTS in Small Animal Surgery

SCHOLARSHIP AWARD £24,100.00 Year one

The Senior Clinical Training Scholarship provides an outstanding opportunity to study for a postgraduate qualification, and is available from January 2022. The Scholar will be trained in all aspects of small animal surgery, including soft tissue and orthopaedics. The training programme is approved by the European College of Veterinary Surgery.

The Scholar will be required to register for the ECVS Diploma in Small Animal Surgery. The training programme requires participation in the Department's clinical service, including the out-of-hours rota, in addition to small-group teaching of veterinary students.

Applicants must be a Member of the Royal College of Veterinary Surgeons. Completion of an ECVS recognised internship and at least one year's experience in practice is required. Full details of the person specification for the Scholarship are supplied in the information pack.

Informal enquiries should be directed to:

Laura Owen (Soft Tissue Surgery) lo247@cam.ac.uk

A SCTS application form (SCTS1) and information pack can be downloaded from the following website: https://www.vet.cam.ac.uk/job

Applicants should supply a completed SCTS Application Form (SCTS1), Curriculum Vitae and Covering Letter giving reasons for wishing to undertake the SCTS in the Department of Veterinary Medicine, University of Cambridge.

Applications should be submitted via e-mail to vetmed@vet.cam.ac.uk with the above documents as one attachment, by the closing date stated.

Please note:

The ability to take up this Scholarship is contingent upon you being able to evidence your right to work in the UK, or through gaining the right to work via the UK immigration system. Evidence will need to be provided before an offer can be made. Regrettably, this Scholarship is not suitable for sponsorship via the Skilled Worker or Temporary Worker visa routes as the minimum requirements cannot be met."

Fixed-term: 3 years.

Interviews will be held on Thursday 11th November 2021

Please quote reference PP28192 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

World first for AI and machine learning to treat COVID-19 patients worldwide

Latest Research in Cambridge - Wed, 15/09/2021 - 17:19

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

Latest Research in Cambridge - Tue, 14/09/2021 - 19:00

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

Latest Research in Cambridge - Thu, 09/09/2021 - 12:59

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

Latest Research in Cambridge - Mon, 06/09/2021 - 15:47

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

Latest Research in Cambridge - Thu, 02/09/2021 - 16:11

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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