Like humans, plants have an ‘internal clock’ that monitors the rhythms of their environment. The authors of a study published today say that now the genetic basis of this circadian system is well understood and there are improved genetic tools to modify it, the clock should be exploited in agriculture – a process they describe as ‘chronoculture’ – to contribute to global food security.

“We live on a rotating planet, and that has a huge impact on our biology – and on the biology of plants. We’ve discovered that plants grow much better when their internal clock is matched to the environment they grow in,” said Professor Alex Webb, Chair of Cell Signalling in the University of Cambridge’s Department of Plant Sciences and senior author of the report.

A plant’s circadian clock plays an important role in regulating many of the functions that affect yield including flowering time, photosynthesis, and water use. The genes controlling the circadian rhythm are similar in all major crop plants – making them a potential target for crop breeders wishing to gain more control over these functions.

Chronoculture could also be applied by adapting crop growing practices to the optimal time of day, to reduce the resources required. The study is published today in the journal Science.

The simplest and easiest approach, say the scientists, would be to use knowledge of a crop’s internal clock to apply water, herbicides or pesticides at the most effective time of day or night. Low-cost technologies including drones and sensors could collect round-the-clock information about plant crop growth and health. Farmers could then receive advice about the best time to apply treatments to their specific crop, for their precise location and weather conditions.

“We know from lab experiments that watering plants or applying pesticides can be more effective at certain times of day, meaning farmers could use less of these resources. This is a simple win that could save money and contribute to sustainability,” said Webb.

He added: “Using water more efficiently is an important sustainability goal for agriculture.”

Webb says that indoor ‘vertical farming’ could also be improved using chronoculture. The approach, mostly used for leafy greens at present, grows crops under highly controlled light and temperature conditions but can also be very energy intensive. With knowledge of the plants’ internal clock and the ability to change it through genetic modification, the lighting and heating cycles could be matched to the plant for highly efficient growth.

“In vertical farming, chronoculture could give total control over the crop. We could breed specific crop plants with internal clocks suited to growing indoors, and optimise the light and temperature cycles for them,” said Webb.

A third potential application of chronoculture is post-harvest, when plants slowly deteriorate and continue to be eaten by pests. There is good evidence that pest damage can be reduced by maintaining the internal rhythms of the harvested plants.

“Plants’ responses to pests are optimised – they’re most resistant to pests at the time of day the pests are active,” said Webb. “So just a simple light in the refrigerated lorry going on and off to mimic the day/ night cycle would use the plants’ internal clock to help improve storage and reduce waste.”

The researchers say that in selecting plants with particular traits such as late flowering time for higher yield, crop breeders have already been unwittingly selecting for the plants with the most suitable internal clock. New understanding of the genes involved in the clock could make this type of breeding much more targeted and effective.

Webb says there are many opportunities for chronoculture to make food production more sustainable. The specifics would be different for every location and crop, and this is where more research is now needed. He is confident that the approach can form part of the solution to feeding our growing population sustainably.

It has been estimated that we will need to produce more food in the next 35 years has ever been produced in human history, given the projected increases in global population and the change in diets as incomes rise.

A similar idea is now being applied in human medicine: ‘chronomedicine’ is finding that drugs are more effective when taken at a specific time of day.

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

Reference
Steed, G. et al: ‘Chronoculture, harnessing the circadian clock to improve crop yield and sustainability.’  Science, April 2021. DOI:10.1126/science.abc9141

Around one in 2,500 children in the UK is born with cystic fibrosis, a hereditary condition that causes the lungs to become clogged up with thick, sticky mucus. The condition tends to decrease life expectancy among patients.

In recent years, M. abscessus, a species of multi-drug resistant bacteria, has emerged as a significant global threat to individuals with cystic fibrosis and other lung diseases. It can cause a severe pneumonia leading to accelerated inflammatory damage to the lungs, and may prevent safe lung transplantation. It is also extremely difficult to treat – fewer than one in three cases is treated successfully.

In a study published today in Science, a team led by scientists at the University of Cambridge examined whole genome data for 1,173 clinical M. abscessus samples taken from 526 patients to study how the organism has evolved – and continues to evolve. The samples were obtained from cystic fibrosis clinics in the UK, as well as centres in Europe, the USA and Australia.

The team found two key processes that play an important part in the organism’s evolution. The first is known as horizontal gene transfer – a process whereby the bacteria pick up genes or sections of DNA from other bacteria in the environment. Unlike classical evolution, which is a slow, incremental process, horizontal gene transfer can lead to big jumps in the pathogen’s evolution, potentially allowing it to become suddenly much more virulent.

The second process is within-host evolution. As a consequence of the shape of the lung, multiple versions of the bacteria can evolve in parallel – and the longer the infection exists, the more opportunities they have to evolve, with the fittest variants eventually winning out. Similar phenomena have been seen in the evolution of new SARS-CoV-2 variants in immunocompromised patients.

Professor Andres Floto, joint senior author from the Centre for AI in Medicine (CCAIM) and the Department of Medicine at the University of Cambridge and the Cambridge Centre for Lung Infection at Royal Papworth Hospital, said: “What you end up with is parallel evolution in different parts of an individual’s lung. This offers bacteria the opportunity for multiple rolls of the dice until they find the most successful mutations. The net result is a very effective way of generating adaptations to the host and increasing virulence.

“This suggests that you might need to treat the infection as soon as it is identified. At the moment, because the drugs can cause unpleasant side effects and have to be administered over a long period of time – often as long as 18 months – doctors usually wait to see if the bacteria cause illness before treating the infection. But what this does is give the bug plenty of time to evolve repeatedly, potentially making it more difficult to treat.”

Professor Floto and colleagues have previously advocated routine surveillance of cystic fibrosis patients to check for asymptomatic infection. This would involve patients submitting sputum samples three or four times a year to check for the presence of M. abscessus infection. Such surveillance is carried out routinely in many centres in the UK.

Using mathematical models, the team have been able to step backwards through the organism’s evolution in a single individual and recreate its trajectory, looking for key mutations in each organism in each part of the lung. By comparing samples from multiple patients, they were then able to identify the key set of genes that enabled this organism to change into a potentially deadly pathogen.

These adaptations can occur very quickly, but the team found that their ability to transmit between patients was constrained: paradoxically, those mutations that allowed the organism to become a more successful pathogen within the patient also reduced its ability to survive on external surfaces and in the air – the key mechanisms by which it is thought to transmit between people.

Potentially one of the most important genetic changes witnessed by the team was one that contributed towards M. abscessus becoming resistant to nitric oxide, a compound naturally produced by the human immune system. The team will shortly begin a clinical trial aimed at boosting nitric oxide in patients’ lung by using inhaled acidified nitrite, which they hope would become a novel treatment for the devastating infection.

The researchers say their findings highlight the need to treat patients with Mycobacterium abscessus infection immediately, counter to current medical practice.

Examining the DNA taken from patient samples is also important in helping understand routes of transmission. Such techniques are used routinely in Cambridge hospitals to map the spread of infections such as MRSA and C. difficile – and more recently, SARS-CoV-2. Insights into the spread of M. abscessus helped inform the design of the new Royal Papworth Hospital building, opened in 2019, which has a state-of-the-art ventilation system to prevent transmission. The team recently published a study showing that this ventilation system was highly effective at reducing the amount of bacteria in the air.

Professor Julian Parkhill, joint senior author from the Department of Veterinary Medicine at the University of Cambridge, added: “M. abscessus can be a very challenging infection to treat and can be very dangerous to people living with cystic fibrosis, but we hope insights from our research will help us reduce the risk of transmission, stop the bug evolving further, and potentially prevent the emergence of new pathogenic variants.”

The team have used their research to develop insights into the evolution of M. tuberculosis – the pathogen that causes TB about 5,000 years ago. In a similar way to M. abscessus, M. tuberculosis likely started life as an environmental organism, acquired genes by horizontal transfer that made particular clones more virulent, and then evolved through multiple rounds of within-host evolution. While M. abscessus is currently stopped at this evolutionary point, M. tuberculosis evolved further to be able to jump directly from one person to another.

Dr Lucy Allen, Director of Research at the Cystic Fibrosis Trust, said: “This exciting research brings real hope of better ways to treat lung infections that are resistant to other drugs. Our co-funded Innovation Hub with the University of Cambridge really shows the power of bringing together world-leading expertise to tackle a health priority identified by people with cystic fibrosis. We’re expecting to see further impressive results in the future coming from our joint partnership.”

The study was funded by the Wellcome Trust, Cystic Fibrosis Trust, NIHR Cambridge Biomedical Research Centre and Fondation Botnar.

Reference
Bryant, JM et al. Stepwise pathogenic evolution of Mycobacterium abscessus. Science; 30 Apr 2021

While research has shown that significant numbers of people fantasise about inflicting harm, little is known about the processes behind such ‘violent ideations’.

A team led by a University of Cambridge professor tracked the self-reported thoughts and experiences of 1,465 young people from schools across the Swiss city of Zurich at the ages of 15, 17 and 20.

Researchers gathered data on whether violent thoughts had occurred in the last 30 days, and the types of bullying or aggression experienced over the last 12 months.

They used questionnaires to probe the levels of aggression (humiliation, beatings, murder) and imagined targets (strangers, friends) within young people’s darkest fantasies.

The team also asked about experiences of 23 forms of ‘victimisation’, such as taunts, physical attacks and sexual harassment by peers, aggressive parenting – yelling, slapping, hitting with a belt – and dating violence eg being pressured into sex.

While the majority of teenagers had been victimised in at least one way, experiencing a range of mistreatment was ‘closely associated’ with a higher likelihood of thinking about killing, attacking or humiliating others.

Boys were more prone to violent thinking in general, but the effect of multiple victimisations on violent fantasies was very similar in both sexes.

Among 17-year-old boys who had not been victimised in the preceding year, the probability of violent fantasies in the last month was 56%.

With every additional type of mistreatment, the probability of violent fantasies increased by up to 8%. Those who listed five forms of victimisation had an 85% probability of having had violent fantasies; for those who listed ten it was 97%.

Among girls the same age, no victimisation experience had a violent fantasy probability of 23%, which increased to 59% in those who listed five types of mistreatment, and 73% in those who said they had suffered ten.

“One way to think about fantasies is as our brain rehearsing future scenarios,” said Prof Manuel Eisner, Director of Cambridge’s Violence Research Centre and lead author of the study published in the journal Aggressive Behavior.

“The increased violent fantasies among those who experience bullying or mistreatment may be a psychological mechanism to help prepare them for violence to come,” he said.

“These fantasies of hitting back at others may have roots deep in human history, from a time when societies were much more violent, and retribution – or the threat of it – was an important form of protection.”

According to Eisner, the research hints at the extent of violent ideation in societies as seemingly peaceful as Switzerland – with murderous thoughts surprisingly commonplace.

“About 25% of all 17-year-old boys and 13% of girls reported having at least one fantasy of killing a person they know during the past 30 days. Close to one in five of all the study participants at that age. These thoughts may be deeply troubling to those who experience them,” he said.

The team – including researchers from the University of Zurich, University of Edinburgh, University of Utrecht, University of Leiden, and Universidad de la Republica – collected and analysed a wealth of data.

As such, they were able to filter out and ‘control’ for other possible triggers for violent thinking in the teenagers. For example, they found that socio-economic status played little role in violent fantasy rates.

The study also shows that ‘adverse life events’ such as financial troubles or parental separation had no significant impact. “Thoughts of killing others are triggered by experiences of interpersonal harm-doing, attacks on our personal identity, rather than noxious stimuli more generally,” said Eisner.

“It’s the difference between conditions that make people angry and upset, and those that make people vengeful.”

By following most of the teenagers to the cusp of adulthood, researchers could track patterns over several years. Overall rates of the most extreme thoughts decreased by the age of 20: only 14% of young men and 5.5% of women had thought about killing someone they know in the past month.

However, the effects of victimisation on violent fantasies did not lessen as they grew up, suggesting the intensity of this psychological mechanism may not fade.

“This study did not examine whether violent ideations caused by victimisation actually lead to violent behaviour. However, a consistent finding across criminology is that victims often become offenders, and vice versa,” said Eisner.

“Fantasies are unrestrained, and the vengeance taken in our minds is often wildly disproportionate to the real-world event which triggered it.

“Studying the mechanisms behind violent fantasies, particularly at a young age, may help with targeted interventions that can stop obsessive rumination turning horribly real.”

The MMRDetect clinical algorithm makes it possible to identify tumours that have ‘mismatch repair deficiencies’ and then improve the personalisation of cancer therapies to exploit those weaknesses.

The study, led by researchers from the University of Cambridge’s Department of Medical Genetics and MRC Cancer Unit, identified nine DNA repair genes that are critical guardians of the human genome from damage caused by oxygen and water, as well as errors during cell division.

The team used a genome editing technology, CRISPR-Cas9, to ‘knock out’ (make inoperative) these repair genes in healthy human stem cells. In doing so, they observed strong mutation patterns, or mutational signatures, which offer useful markers of those genes and the repair pathways they are involved in, failing.

The study, funded by Cancer Research UK and published today in the journal Nature Cancer, suggests that these signatures of repair pathway defects are on-going and could therefore serve as crucial biomarkers in precision medicine.

Senior author, Dr Serena Nik-Zainal, a Cancer Research UK Advanced Clinician Scientist at Cambridge University’s MRC Cancer Unit, said: “When we knock out different DNA repair genes, we find a kind of fingerprint of that gene or pathway being erased. We can then use those fingerprints to figure out which repair pathways have stopped working in each person’s tumour, and what treatments should be used specifically to treat their cancer.”

The new computer algorithm, MMRDetect, uses the mutational signatures that were identified in the knock out experiments, and was trained on whole genome sequencing data from NHS cancer patients in the 100,000 Genomes Project, to identify tumours with ‘mismatch repair deficiency’ which makes them sensitive to checkpoint inhibitors, immunotherapies. Having developed the algorithm on tumours in this study, the plan now is to roll it out across all cancers picked up by Genomics England.

The breakthrough demonstrates the value of researchers working with the 100,000 Genomes Project, a pioneering national whole genome sequencing endeavour.

Parker Moss, Chief Commercial and Partnerships Officer at Genomics England, said: “We are very excited to see such impactful research being supported by the 100,000 Genomes Project, and that our data has helped to develop a clinically significant tool. This is a fantastic example of how the sheer size and richness of the 100,000 Genomes Project data can contribute to important research.

“The outcomes from Dr Nik-Zainal and her team’s work demonstrate perfectly how quickly and effectively we can return value to patient care by bringing together a community of leading researchers through Genomics England’s platform.”

The study offers important insights into where DNA damage comes from in our bodies. Water and oxygen are essential for life but are also the biggest sources of internal DNA damage in humans.

Dr Nik-Zainal said: “Because we are alive, we need oxygen and water, yet they cause a constant drip of DNA damage in our cells. Our DNA repair pathways are normally working to limit that damage, which is why, when we knocked out some of the crucial genes, we immediately saw lots of mutations.”

“Some DNA repair genes are like precision tools, able to fix very specific kinds of DNA damage. Human DNA has four building blocks: adenine, cytosine, guanine and thymine. As an example, the OGG1 gene has a very specific role of fixing guanine when it is damaged by oxygen. When we knocked out OGG1, this crucial defence was severely weakened resulting in a very specific pattern of guanines that had mutated into thymines throughout the genome.”

To be most effective, the MMRDetect algorithm could be used as soon as a patient has received a cancer diagnosis and their tumour characterised by genome sequencing. The team believes that this tool could help to transform the way a wide range of cancers are treated and save many lives.

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Determining the right treatments for patients will give them the best chance of surviving their disease. Immunotherapy in particular can be powerful, but it doesn’t work on everyone, so figuring out how to tell when it will work is vital to making it the most useful treatment it can be.

“Our ability to map and mine useful information from the genomes of tumours has improved massively over the past decade. Thanks to initiatives like the 100,000 Genomes Project, we are beginning to see how we might use this information to benefit patients. We look forward to seeing how this research develops, and its possibilities in helping future patients.”

This study was funded by Cancer Research UK (CRUK), Wellcome, Medical Research Council, Dr Josef Steiner Foundation and supported by the Cambridge NIHR Biomedical Research Campus.

Reference

Xueqing Zou et al., ‘A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage‘, Nature Cancer (26 April 2021). DOI: 10.1038/s43018-021-00200-0. 

Two hundred and nine senior scientists from across Europe were awarded grants in today’s announcement, representing a total of €507 million in research funding. The UK has 51 grantees in this year’s funding round, the most of any ERC participating country.

ERC grants are awarded through open competition to projects headed by starting and established researchers, irrespective of their origins, who are working or moving to work in Europe. The sole criterion for selection is scientific excellence. ERC Advanced Grants are designed to support excellent scientists in any field with a recognised track record of research achievements in the last ten years. Apart from strengthening Europe’s knowledge base, the new research projects will also lead to the creation of some 1,900 new jobs for post-doctoral fellows, PhD students and other research staff.

Professor Melinda Duer from the Yusuf Hamied Department of Chemistry has been awarded a grant for her EXTREME project to explore the chemistry that happens when a biological tissue stretches or breaks.

So-called mechanochemistry leads to molecules being generated within the tissue that may be involved in communicating tissue damage to cells. Detecting and understanding this chemistry is highly relevant for understanding ageing, and for developing new therapeutics for degenerative diseases and cancer.

“This award means I can do the research I’ve been dreaming about for the last ten years,” said Duer. “I am extremely grateful to the European Research Council for giving me this amazing opportunity. The ERC is one of the few organisations that understands the need for longer-term funding for high-risk, high-reward research, which is essential for this project. I really couldn’t be more delighted and I can’t wait to get started!”

Professor Manish Chhowalla, from the Department of Materials Science and Metallurgy, received funding for his 2D-LOTTO project, for the development of energy-efficient electronics.

“This grant will enable our research group to realise the next generation of energy-efficient electronics based on two-dimensional semiconductors,” he said. “The funding will also support a team of students, early career researchers and senior academics to address the challenges of demonstrating practical tunnel field effect transistors.”

Professor Henning Sirringhaus from the Cavendish Laboratory received funding for his NANO-DECTET project, for the development of next-generation energy materials. “Worldwide, only about a third of primary energy is converted into useful energy services: the other two thirds are wasted as heat in the various industrial, transportation, residential energy conversion and electricity generation processes,” said Sirringhaus. “Given the urgent need to mitigate the dangerous consequences of climate change, a waste of energy on this scale needs to be addressed immediately.

“Thermoelectric waste-heat-to-electricity conversion could offer a potential solution, but the performance of thermoelectric materials is currently insufficient. In this project we will use the unique physics of molecular organic semiconductors, as well as hybrid organic-inorganic semiconductors, to make efficient, low-temperature thermoelectric materials.”

Professor Marcos Martinon-Torres from the Department of Archaeology received funding for his REVERSEACTION project, which will study how societies in the past cooperated. “Many prehistoric societies did pretty well at maintaining rich and complex lives without the need for permanent power hierarchies and coercive authorities,” he said. “Arguably, they chose to cooperate, and not just to ensure survival. The lack of state structures did not stop them from developing and sustaining complex technologies, making extraordinary artefacts that required exotic materials, challenging skills and labour arrangements. I’m keen to understand why, but also how they managed.

“This grant couldn’t have come at a better time, as collective action is increasingly recognised as the only way to tackle some of our greatest global concerns, and there is value in studying how people collaborated in the past. With our labs freshly revamped through our recent AHRC infrastructure grant, we are ready to take on a new large-scale, challenging archaeological science project.”

Professor Marta Mirazon Lahr, also from the Department of Archaeology, was awarded funding for her NGIPALAJEM project, which will bring a new understanding of how the evolution of our species is part of a broader and longer African evolutionary landscape.

“My research is in human evolution, a field that advances through technical breakthroughs, new ideas, and critically, new fossils,” said Lahr. “A big part of my work is to find new hominin fossils in Africa, which requires not only supportive local communities and institutions, but long-term planning and implementation, a dedicated team, significant funds and the time to excavate, study, compare and interpret new discoveries. This new grant from the ERC gives me all this and more – and I just can’t wait to get started!”

Professor Richard Samworth’s RobustStats project will develop robust statistical methodology and theory for large-scale data. “Large-scale data are usually messy: they may be collected under different conditions, and data may be missing or corrupted, which makes it difficult to draw reliable conclusions,” said Samworth, from the Department of Pure Mathematics and Mathematical Statistics. “This grant will allow me to focus my time on developing robust statistical methodology and theory to address these challenges. Equally importantly, I will be able to build a group of PhD students and post-docs that will dramatically increase the scale and scope of what we are able to achieve.

Professor Zoran Hadzibabic from the Cavendish Laboratory was awarded funding for his UNIFLAT project. One of the great successes of the last-century physics was recognising that complex and seemingly disparate systems are fundamentally alike. This allowed the classification of the equilibrium states of matter into classes based on their basic properties. At the heart of this classification is the universal collective behaviour, insensitive to the microscopic details, displayed by systems close to phase transitions.

A grand challenge for modern physics is to achieve such a feat for the far richer world of the nonequilibrium collective phenomena. “Our ambition is to make a leading contribution to this worldwide effort, through a series of coordinated experiments on homogeneous atomic gases in two-dimensional (2D) geometry,” said Hadzibabic. “Specifically, we will study in parallel three problems – the dynamics of the topological Berezinskii-Kosterlitz-Thouless phase transition, turbulence in driven systems, and the universal spatiotemporal scaling behaviour in isolated quantum systems far from equilibrium. Each of these topics is fascinating and of fundamental importance in its own right, but beyond that we will experimentally establish an emerging picture that connects them.”

Dr Helen Williams from the Department of Earth Sciences said: “By funding the EarthMelt project, the ERC has given me the amazing opportunity to study the early evolution of the Earth and its transition from a largely molten state to the habitable planet we know today. This funding will also help me to develop exciting new instrumentation and analytical techniques, and, most importantly, mentor and support the next generation of PhD students and postdoctoral researchers working in geochemistry.”

Professor Sir Richard Friend from the Cavendish Laboratory has been awarded funding for his Spin Control in Radical Semiconductors (SCORS) project, which will explore the electronic properties of organic semiconductors that have an unpaired electron to give net magnetic spin. The project is based on a recent discovery that this unpaired electron can couple strongly to light, allowing very efficient luminescence in LEDs. Friend’s group will explore new combinations of optical excited states with magnetic spin states. This will allow new designs for LEDs and solar cells, and opportunities to control the ground state spin polarisation in spintronic devices.

Professor Christopher Hunter’s InfoMols project is focused on synthetic information molecules. “The aim of our project is replication and evolution with artificial polymers,” said Hunter, from the Yusuf Hamied Department of Chemistry. “The timeframe for achieving such a breakthrough is unpredictable, and it is the flexibility provided by an ERC award that makes tackling such challenging targets possible.”

Professor Mark Gross from the Department of Pure Mathematics and Mathematical Statistics received funding for his Mirror symmetry in Algebraic Geometry (MSAG) project, and Professor Geoffrey Khan from the Faculty of Asian and Middle Eastern Studies was awarded funding for ALHOME: Echoes of Vanishing Voices in the Mountains: A Linguistic History of Minorities in the Near East.

The University of Cambridge study found that pupils who learn about the value of languages, how languages shape personal identity, and their impact on social cohesion, feel much more positive about subjects like French, German and Spanish; compared with those who only learn the speaking and writing skills prescribed by the national curriculum.

Researchers conducted a trial with 270 pupils at four English secondary schools over a full academic year. While all the pupils received traditional language lessons, some also participated in activities which explored the value of multilingualism and its significance in their own communities and lives. Pupils who were exposed to this extended programme showed significantly more belief in their ability to learn a language, and were up to 35% more likely to express positive sentiments about studying languages, by the end of the year.

The researchers argue that encouraging young people to form ‘multilingual identities’ could help to reverse the national crisis in language learning. According to the British Council’s annual Language Trends survey, only 51% of pupils opt to study a foreign language to GCSE: far off the Government’s Ebacc target of 75% of pupils by 2022.

Dr Karen Forbes, from the Faculty of Education, University of Cambridge, said: “Young people in England often wonder why they should study languages given that English is used internationally. The answer they usually get is that it might be useful in the future, which is a pretty unpersuasive argument when you’re 14. We found that if we encourage them to reflect on how languages relate to them personally, they are much more likely to respond positively to language learning. This seems crucial if we want to reverse the decline in these subjects.”

The trial used downloadable materials developed by the University of Cambridge-based ‘We Are Multilingual’ project, which aims to encourage young people both to value multilingualism, and to appreciate that everyone uses more than one ‘language’ in the broadest sense.

Dr Linda Fisher, University Reader in Languages Education, said: “Everyone depends on a repertoire of communication, whether that involves a second language, a particular dialect, non-verbal signs, or something like computer code. Helping young people to realise that is key to showing them that they can ‘do’ languages. Language education needs to be about more than just vocab and verbs.”

The pupils were in Year 9 (ages 13 to 14): the final year of compulsory language education before they choose subjects for GCSE. They were drawn from four very different schools in London and the East of England.

Participants were split into three groups. A control group continued with their regular lessons in French, German or Spanish; while two intervention groups took six, one-hour modules exploring multilingualism over the course of the year. These covered topics such as ‘Why learn languages?’, different types of language and dialect, and the relationship between language, cultural identity and belonging.

The two intervention groups engaged with this material at different levels. While a partial intervention group completed follow-up activities designed to reinforce some of the core ideas, the full intervention group examined how the topics affected them personally. For instance, in one exercise, this latter group was asked to investigate what different languages their own classmates knew; in another they compiled photographs showing how different languages were used where they lived.

The researchers used surveys, both before and after the academic year, to measure how far pupils’ attitudes towards language learning changed. For example, pupils were asked to rate how ‘multilingual’ they considered themselves on a scale of 0-100. They were also asked about their beliefs regarding languages, those of their parents and friends, and how competent and confident they felt as language-learners. In addition, pupils were asked to complete the blanks in statements such as: ‘Learning a foreign language is like… because…’

By the end of the trial, those in the partial and full intervention groups consistently responded more positively to statements about the importance of languages than those in the control group. They also showed much more self-belief about their ability to learn languages.

The most significant findings, however, came from the full intervention group. For example, the extent to which pupils in this group self-identified as multilingual rose on average by 11 percentage points over the year, compared with a 2.5-point rise in the partial intervention, and a one-point fall in the control group.

Significantly, pupils in the full intervention expressed much more enthusiasm for learning languages, and took greater pride in the idea of doing so. When asked to complete different statements regarding their feelings about languages, the percentage of positive responses in this group rose between 15% and 35% across the year, compared with much smaller changes in the other groups.

“It seems pretty clear that pupils who are encouraged to think about what languages mean to them personally are more interested in studying them, and see themselves as more multilingual,” Forbes said.

Fisher added: “The evidence suggests that we are missing an opportunity to teach children about languages, as well as how to speak and write them. Integrating that into the curriculum could potentially lead to very positive transformations in pupils’ attitudes towards language learning.”

The research is published in The Language Learning Journal.

Low oxygen in the womb – known as chronic fetal hypoxia – is one of the most common complications in human pregnancy. It can be diagnosed when a routine ultrasound scan shows that the baby is not growing properly and is caused by a number of conditions including pre-eclampsia, infection of the placenta, gestational diabetes or maternal obesity.

The new results show that chronic fetal hypoxia leads to a reduced density of blood vessels, and a reduced number of nerve cells and their connections in parts of the offspring’s brain. When the offspring reaches adulthood, its ability to form lasting memories is reduced and there is evidence of accelerated brain ageing.

Vitamin C, an anti-oxidant, given to pregnant rats with chronic fetal hypoxia was shown to protect the future brain health of the offspring. The results are published today in the journal FASEB J.

“It’s hugely exciting to think we might be able to protect the brain health of an unborn child by a simple treatment that can be given to the mother during pregnancy,” said Professor Dino Giussani from the University of Cambridge’s Department of Physiology, Development and Neuroscience, who led the study.

The researchers used Vitamin C because it is a well-established and used anti-oxidant. However, only high doses were effective, which could cause adverse side-effects in humans. Follow-up studies are now searching for alternative anti-oxidants to treat chronic fetal hypoxia in humans.

To conduct the research, a group of pregnant rats were kept in ambient air with 13% oxygen – causing hypoxic pregnancies. The rest were kept in normal air (21% oxygen). Half of the rats in each group were given Vitamin C in their drinking water throughout the pregnancy. Following birth, the baby rats were raised to four months old, equivalent to early adulthood in humans, and then performed various tests to assess locomotion, anxiety, spatial learning and memory.

The study found that rats born from hypoxic pregnancies took longer to perform the memory task, and didn’t remember things as well. Rats born from hypoxic pregnancies in which mothers had been given Vitamin C throughout their pregnancy performed the memory task just as well as offspring from normal pregnancies.

Analysing the brains of the rat offspring, the researchers found that the hippocampus – the area associated with forming memories – was less developed in rats from hypoxic pregnancies.

In deeper analysis, the scientists showed that hypoxic pregnancy causes excess production of reactive oxygen species, called ‘free radicals’, in the placenta. In healthy pregnancy the body keeps the level of free radicals in check by internal anti-oxidant enzymes, but excess free radicals overwhelm these natural defences and damage the placenta in a process called ‘oxidative stress’.  This reduces blood flow and oxygen delivery to the developing baby.

In this study, placentas from the hypoxic pregnancies showed oxidative stress, while those from the hypoxic pregnancies supplemented with Vitamin C looked healthy.

Taken together, these results show that low oxygen in the womb during pregnancy causes oxidative stress in the placenta, affecting the brain development of the offspring and resulting in memory problems in later life.

“Chronic fetal hypoxia impairs oxygen delivery at critical periods of development of the baby’s central nervous system. This affects the number of nerve connections and cells made in the brain, which surfaces in adult life as problems with memory and an earlier cognitive decline,” said Dr Emily Camm from Cambridge’s Department of Physiology, Development and Neuroscience, first author of the report, who has recently taken up a new position at The Ritchie Centre in Australia.

The interaction between our genes and lifestyle plays a role in determining our risk of disease as adults. There is also increasing evidence that the environment experienced during sensitive periods of fetal development directly influences our long-term health – a process known as ‘developmental programming.’

Brain health problems that may start in the womb due to complicated pregnancy range from attention deficit hyperactivity disorder, to brain changes in later life that have been linked with Alzheimer’s disease.

“In medicine today there has to be a shift in focus from treatment of the disease, when we can do comparatively little, to prevention, when we can do much more. This study shows that we can use preventative medicine even before birth to protect long term brain health,” said Giussani.

The research was funded by The British Heart Foundation and The Medical Research Council, and the programme of work was approved by the University of Cambridge Animal Welfare and Ethical Review Board.

Reference
Camm et al: ‘Maternal antioxidant treatment protects adult offspring against memory loss and hippocampal atrophy in a rodent model of developmental hypoxia.’ The FASEB Journal, April 2021. DOI: 10.1096/fj.202002557RR

Led by 2019 Physics Nobel Laureate Professor Didier Queloz, the Cambridge Initiative for Planetary Science and Life in the Universe will be the driving force for the development of a new Cambridge research community investigating life in the Universe, from understanding how it emerged on Earth to examining the processes that could make other planets suitable for life.

The initiative comes at a crucial moment in science, as scientists are able to study exoplanets – planets orbiting stars other than our Sun – in ever-greater detail, and outstanding progress is being made in prebiotic chemistry: carefully-regulated laboratory experiments to recreate the conditions when life first formed on Earth.

In addition, the recent successful landing of the Mars 2020 Perseverance Rover set in motion one of the greatest international scientific endeavours of recent decades. Within the next ten years, samples returned from a four-billion-year-old lake deposit on Mars will offer a unique window on the Solar System as it was when life originated on Earth and could provide evidence of ancient life on the Red Planet.

“These recent revolutions and future perspectives offered by next-generation space missions mean that the planets are aligned for us to create a vibrant new field at the cutting edge of modern science,” said Queloz, from Cambridge’s Cavendish Laboratory and Director of the Initiative.

Building on the University’s research excellence and enhancing the multidisciplinary research conducted in various departments of the School of the Physical Sciences, the focus of the research within the new Initiative will be to understand the origins and physical properties of planets throughout the Universe, as well as the chemical and biological processes capable of starting and sustaining life.

“By bringing together chemists, geologists, biologists, and astrophysicists to work creatively together toward a common goal, the Initiative will ensure we truly exploit the full potential of this exciting new field of research, bringing us closer to understanding life in the Universe and finding life beyond Earth,” said Queloz.

The School of the Physical Sciences and its various departments (Cavendish Laboratory, Chemistry, Applied Mathematics and Theoretical Physics, Earth Sciences and the Institute of Astronomy) recently committed to an initial funding package that will support the Initiative as it builds the foundations of its vision and will create the conditions for its research and educational ambitions to grow and develop.

Professor Nigel Peake, Head of the School of the Physical Sciences, said: “During the last decades our understanding of the microbiology of life has made spectacular progress, but knowledge on origins of life on Earth, and more generally in the Universe, are still nascent. This is about to change. I am proud that Cambridge is leading the way to a radically new approach based on a convergence of recent results in astrophysics, planetology and molecular chemistry.

“With the Cambridge Initiative for Planetary Science and Life in the Universe, we will provide the infrastructure that will allow scholars from various disciplines to combine their interests to address the fundamental question of our origins in the Universe. This sets the scene for a revolution to come.”

For more information, news and updates about the Cambridge Initiative for Planetary Science and Life in the Universe, visit www.iplu.phy.cam.ac.uk.

A team of scientists led by Professor Eske Willerslev in the University of Cambridge’s Department of Zoology and the Lundbeck Foundation GeoGenetics Centre, University of Copenhagen, have recreated the genomes of animals, plants and bacteria from microscopic fragments of DNA found in the remote Chiquihuite Cave in Mexico.

The findings have been described as the ‘moon landings of genomics’, because researchers will no longer have to rely on finding and testing fossils to determine genetic ancestry and connections.

The results, published today in the journal Current Biology, are the first time environmental DNA has been sequenced from soil and sediment. They include the ancient DNA profile of a Stone Age American black bear taken from samples in the cave.

Working with highly fragmented DNA from soil samples means scientists no longer have to rely on DNA samples from bone or teeth for enough genetic material to recreate a profile of ancient DNA.

The samples included faeces and droplets of urine from an ancestor of the American black bear, which allowed the scientists to recreate the entire genetic code of two species of the animal: the Stone Age American black bear, and a short-faced bear called Arctodus simus that died out 12,000 years ago.

Professor Willerslev said: “When an animal or a human urinates or defecates, cells from the organism are also excreted. We can detect the DNA fragments from these cells in the soil samples and have now used these to reconstruct genomes for the first time. We have shown that hair, urine and faeces all provide genetic material which, in the right conditions, can survive for much longer than 10,000 years.

“Analysis of DNA found in soil could have the potential to expand the narrative about everything from the evolution of species to developments in climate change – fossils will no longer be needed.”

Chiquihuite Cave is a high-altitude site, situated 2,750 metres above sea level. DNA of mice, black bears, rodents, bats, voles and kangaroo rats was also found. The scientists say that DNA fragments in sediment will now be able to be tested in many former Stone Age settlements around the world.

Professor Willerslev said: “Imagine the stories those traces could tell. It’s a little insane – but also fascinating – to think that, back in the Stone Age, these bears urinated and defecated in the Chiquihuite Cave and left us the traces we’re able to analyse today.”

Reference

Petersen, M.K. et al, Environmental genomics of Late Pleistocene black bears and giant short-faced bears. Current Biology, April 2021. DOI: 10.1016/j.cub.2021.04.027

Adapted from a press release by St John’s College, Cambridge.

The results, reported in the journal Physical Review Letters, could be used to design new types of materials and quantum technology devices. The researchers, from the University of Cambridge, captured the movement of the atoms at speeds that are eight orders of magnitude too fast for conventional microscopes.

Two-dimensional materials, such as graphene, have the potential to improve the performance of existing and new devices, due to their unique properties, such as outstanding conductivity and strength. Two-dimensional materials have a wide range of potential applications, from bio-sensing and drug delivery to quantum information and quantum computing. However, in order for two-dimensional materials to reach their full potential, their properties need to be fine-tuned through a controlled growth process.

These materials normally form as atoms ‘jump’ onto a supporting substrate until they attach to a growing cluster. Being able to monitor this process gives scientists much greater control over the finished materials. However, for most materials, this process happens so quickly and at such high temperatures that it can only be followed using snapshots of a frozen surface, capturing a single moment rather than the whole process.

Now, researchers from the University of Cambridge have followed the entire process in real time, at comparable temperatures to those used in industry.

The researchers used a technique known as ‘helium spin-echo’, which has been developed in Cambridge over the last 15 years. The technique has similarities to magnetic resonance imaging (MRI), but uses a beam of helium atoms to ‘illuminate’ a target surface, similar to light sources in everyday microscopes.

“Using this technique, we can do MRI-like experiments on the fly as the atoms scatter,” said Dr Nadav Avidor from Cambridge’s Cavendish Laboratory, the paper’s senior author. “If you think of a light source that shines photons on a sample, as those photons come back to your eye, you can see what happens in the sample.”

Instead of photons however, Avidor and his colleagues use helium atoms to observe what happens on the surface of the sample. The interaction of the helium with atoms at the surface allows the motion of the surface species to be inferred.

Using a test sample of oxygen atoms moving on the surface of ruthenium metal, the researchers recorded the spontaneous breaking and formation of oxygen clusters, just a few atoms in size, and the atoms that quickly diffuse between the clusters.

“This technique isn’t a new one, but it’s never been used in this way, to measure the growth of a two-dimensional material,” said Avidor. “If you look back on the history of spectroscopy, light-based probes revolutionised how we see the world, and the next step – electron-based probes – allowed us to see even more.

“We’re now going another step beyond that, to atom-based probes, allowing us to observe more atomic scale phenomena. Besides its usefulness in the design and manufacture of future materials and devices, I’m excited to find out what else we’ll be able to see.”

The research was conducted in the Cambridge Atom Scattering Centre and supported by the Engineering and Physical Sciences Research Council (EPSRC).

Reference:
Jack Kelsall et al. ‘Ultrafast diffusion at the onset of growth: O=Ru(0001).’ Physical Review Letters (2021). DOI: 10.1103/PhysRevLett.126.155901

When researchers applied the technique to analysing samples obtained using the ‘pill on a string’ diagnostic tool Cytosponge, they found that it was capable of reducing by half pathologists’ workload while matching the accuracy of even experienced pathologists.

Early detection of cancer often leads to better survival because pre-malignant lesions and early stage tumours can be more effectively treated. This is particularly important for oesophageal cancer, the sixth most common cause for cancer-related deaths. Patients usually present at an advanced stage with swallowing difficulties and weight loss. The five-year overall survival can be as low as 13%.

One main subtype of oesophageal cancer is preceded by a condition known as Barrett oesophagus, in which cells in the lining of the oesophagus change shape. Barrett oesophagus occurs in patients with Gastro-oesophageal Reflux Disease (GORD), a digestive disorder where acid and bile from the stomach return into the oesophagus leading to heartburn symptoms. In Western countries, 10-15% of the adult population are affected by GORD and are hence at an increased risk of having Barrett oesophagus.

At present Barrett oesophagus can only be detected by a gastroscopy and tissue biopsy. Researchers at the University of Cambridge have developed a far-less invasive diagnostic tool called the Cystosponge – a ‘pill on a string’ that dissolves in the stomach and which, as it is withdrawn, picks up some cells from the lining of the oesophagus. These cells are then stained using a laboratory marker called TFF3 and can then by examined under a microscope.

Now, in a study published today in Nature Medicine, a team at Cambridge has applied deep learning techniques to the sample analysis, stratifying patients into eight triage classes that determine whether a patient sample requires manual review or if automated review would suffice. The algorithms were trained using 4,662 pathology slides from 2,331 patients.

Professor Rebecca Fitzgerald from the MRC Cancer Unit at the University of Cambridge, who developed the Cytosponge and worked with the AI team, said: “Any system that supports clinical decisions needs to balance its performance against workload reduction and potential economic impact. Replacing pathologists entirely could lead to substantial workload reduction and speed up diagnoses, but such an approach would only be viable if the performance remains comparable to that of human experts and there are regulatory hurdles to overcome.”

For the analysis of Cytosponge-TFF3 samples, the triaging approach showed several benefits, substantially reducing workload and matching the sensitivity and specificity of experienced pathologists. Sensitivity is the ‘true positive’ rate – that is, how often a test correctly generates a positive result for people who have Barrett oesophagus. Specificity, on the other hand, measures a test’s ability to correctly generate a negative result for people who don’t have the disease.

The researchers showed that a fully manual review by a pathologist achieves 82% sensitivity and 93% specificity. In a fully automated approach, they observed a sensitivity of 73% and a specificity of 93%. The team was able to demonstrate that using a triage-driven approach, up to two-thirds of cases can be reviewed automatically while achieving a sensitivity of 83% and specificity of 93%. The team estimates that this approach would reduce workload for the pathologists by 57%.

The team were able to build into their algorithm problem-solving techniques applied by pathologists familiar with Cytosponge-TFF3 samples. This meant that the algorithms were interpretable – in other words, a clinician would be able to understand why they had reached a particular decision. This is important for accountability.

Dr Florian Markowetz from the CRUK Cambridge Institute, who led the work on the AI algorithm, said: “We’ve shown that it’s possible to use computer-aided tools to streamline identification of people at risk of Barrett oesophagus. By semi-automating the process, we can reduce the workload by more than half while retaining the accuracy of a skilled pathologist. This could potentially speed up the diagnosis of Barrett oesophagus and, potentially, the identification of those individuals at greatest risk of oesophageal cancer.”

The team say that this triage-driven approach could be applied beyond the Cytosponge to a number of tests for other conditions such as pancreatic cancer, thyroid cancer or salivary gland malignancies.

The research was supported by Cancer Research UK, the Medical Research Council and Cambridge University Hospitals NHS Foundation Trust.

Reference
Gehrung, M et al. Triage-driven diagnosis of Barrett esophagus for early detection of esophageal adenocarcinoma using deep learning. Nat Med; 15 Apr 2021; DOI: 10.1038/s41591-021-01287-9

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

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

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

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

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

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

The women then repeated the stop-signal task again.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

CRISPR-Cas9 genome editing is a widely used research tool which allows scientists to remove and replace sections of DNA in cells, allowing them, for example, to study the function of a given gene or to repair mutations. Last year the researchers who developed CRISPR-Cas9 were awarded the Nobel Prize in Chemistry.

In the study published in the journal PNAS, scientists retrospectively analysed data from previous research in which they had studied the role of the OCT4 protein in human embryos during the first few days of development.

The team found that while the majority of CRISPR-Cas9-induced mutations were small insertions or deletions, in approximately 16% of samples there were large unintended mutations that would have been missed by conventional methods to assess DNA changes.

Research is ongoing to understand the exact nature of the changes at the target sites, but this could include deletions of sections of DNA or more complex genomic rearrangements.

The discovery highlights the need for researchers who use CRISPR-Cas9-mediated genome editing to edit human cells, whether somatic or germline, to be aware of and test for these potential unintended consequences. This is even more essential if they hope their work will be used clinically, as unintended genetic changes like this could lead to diseases like cancer.

“Other research teams have reported these types of unintended mutations in human stem cells, cancer cells and other cellular contexts, and now we’ve detected them in human embryos,” said Professor Kathy Niakan, group leader of the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute and Professor of Reproductive Physiology at the University of Cambridge, and senior author of the study.

“This work underscores the importance of testing for these unintended mutations to understand exactly what changes have happened in any human cell type.”

The researchers have developed an open-source computational pipeline to identify whether CRISPR-Cas9 has caused unintended on-target mutations based on different types of next-generation sequencing data.

“We and others are trying to develop and refine the tools to assess these complex mutations, “ added Niakan.

“It is important to understand these events, how they arise and their frequency, so we can appreciate the current limitations of the technology and inform strategies to improve it in the future to minimise these mutations.”

Gregorio Alanis-Lobato, lead author and former postdoctoral training fellow in the Human Embryo and Stem Cell Laboratory at the Crick, said: “Conventional tests used to check the accuracy of CRISPR-Cas9 can miss the types of unintended on-target mutations we identified in this study. There’s still so much for us to learn about the effects of CRISPR-Cas9 technology and while this valuable tool is refined, we need to thoroughly examine all changes.”

There are important ongoing debates around the safety and ethics of using CRISPR-Cas9 genome editing on human embryos for reproductive purposes. And in 2019, there was international condemnation of the work of a researcher in China who edited embryos which led to the birth of twins. In the UK, its use on human embryos is closely regulated and is only allowed for research purposes. Research is restricted to the first 14 days of development and embryos are not allowed to be implanted into a womb.

The data for this work related to embryos previously studied by the Crick’s Human Embryo and Stem Cell Laboratory. The embryos were at the blastocyst stage of early development, consisting of around 200 cells. They had been donated to research by people undergoing in vitro fertilisation (IVF) and were not needed during the course of their treatment.

The research was led by scientists at the Francis Crick Institute, in collaboration with Professor Dagan Wells at the University of Oxford. Kathy Niakan is Director of the University of Cambridge’s Centre for Trophoblast Research, and Chair of the Cambridge Strategic Research Initiative in Reproduction.

Reference
Alanis-Lobato, G., et al: Frequent loss-of-heterozygosity in CRISPR-Cas9-edited early human embryos. PNAS, April 2021. DOI: 10.1073/pnas.2004832117

Adapted from a press release by the Francis Crick Institute.

The research, which used data from around 3,500 young people in Ethiopia, India, Peru and Vietnam, shows that promising but poorer students ‘fall away’ during their school years, as challenges associated with their socio-economic circumstances gradually erode their potential. Among children who showed similar levels of ability aged 8, for example, the wealthiest were often over 30 percentage points more likely than the least-wealthy to enter all forms of tertiary education: including university, technical colleges, and teacher training.

Even when they focused only on students who complete secondary school with comparable levels of learning, the researchers found that those from wealthier backgrounds were still more likely to progress to higher education. They describe their findings, reported in the British Education Research Journal, as indicative of the ‘protective effect’ of wealth in relation to academic advantage.

The study was undertaken by the Research in Equitable Access and Learning (REAL) Centre at the Faculty of Education. Dr Sonia Ilie, its lead author, said: “In many lower-income countries, low socio-economic status is a continual barrier to young people’s attainment. What is clear is that these inequalities in higher education access have nothing to do with ability: this is about systems which are consistently failing poorer children.”

The data used in the research was from Young Lives, an international childhood poverty study which is tracking two cohorts of young people from Ethiopia, India, Peru and Vietnam. The Cambridge researchers focused on the group born in 1994/5. Young Lives includes information about education and attainment at ages 8, 12, 15, 19 and 22, and importantly therefore includes the many young people in lower-income countries who may enter higher education after age 19.

The researchers started by comparing basic entry rates into higher education among the poorest 25% and wealthiest 25% of participants. The percentage point gap between these quartiles was 45 in both India and Peru, 41 in Vietnam, and 17 in Ethiopia.

They then analysed higher education progression rates among increasingly comparable groups of students. First, they focused on those with similar demographic characteristics (such as gender, ethnicity, and whether they lived in urban or rural settings). They then progressively added more information about their education to examine students who were both in school, and achieving certain attainment levels, aged 8, 12 and 15.

The gap between the poorest and richest students’ likelihood of enrolling in higher education narrowed steadily as each level of information was factored in. Given the disparity in the ‘raw’ wealth gap, this indicates that children from poor backgrounds often fail to progress because they drop out, or under-achieve, throughout primary and secondary school. It also suggests that factors such as a person’s gender interact with their socio-economic status to influence their likelihood of progressing to higher education.

Crucially, however, a gap still existed between rich and poor even among students who finished secondary school with comparable levels of learning. The size of the remaining gap reflected the complexities of each country’s higher education systems, but showed that at the same level of schooling and learning, wealth played this protective effect.

The study also analysed the progress of ‘high-promise’ children. The researchers identified all children who had achieved a certain level of literacy at age 8, and then used numeracy and maths scores to compare the educational trajectories of the richest and poorest among this group.

Overall, the attainment gap between high-promise children from the top and bottom wealth quartiles widened during school, even though their test scores were similar at age 8. Ultimately, many more high-promise children from the richest quartile entered higher education compared with the poorest: the percentage point gap between the two groups was 39 in Peru, 32 in India and Vietnam, and 15 in Ethiopia.

“Even among children who do well to begin with, poverty clearly becomes an obstacle to progression,” Ilie said. “The reverse also applies: if they are wealthy, even children with initially lower levels of learning catch up with their poorest peers. This is what we mean by the protective effect of wealth.”

The study says that the first priority in addressing the higher education wealth gap should be targeted investment in primary education for the very poorest. This is already an emerging policy focus in many lower-income countries, where disadvantaged children, even if they go to school, often have poor learning outcomes. The reasons for this, documented in several other studies, include limited educational resources and support at home, and practical difficulties with school attendance.

The findings also indicate, however, that targeted support should continue during secondary education, where wealth-related barriers persist. In addition, the residual wealth gap even among those who finish secondary school highlights a need for initiatives that will reduce the cost of higher education for disadvantaged students. The study suggests that means-tested grants may be one viable solution, but further evidence is required. It also warns that at present, taxation-based funding for higher education will essentially ‘subsidise a socio-economic elite’, while tuition fees will further prohibit access for the poorest.

Professor Pauline Rose, Director of the REAL Centre, said: “If we want to equalise opportunities at the point of entry into higher education, we have to intervene early, when the wealth gaps emerge. This study shows that targeted and sustained interventions and funding are needed for the poorest students not only in their earliest years, but throughout their educational careers.”

I am used to sceptical looks when I talk to scientists about my work with religious communities. They have reason to see science as under threat from zealots: examples abound, from the treatment of Galileo Galilei to vaccine aversion. But faith communities can feel the same way about scientists. Even if they disagree on important topics, it’s both possible and essential to collaborate on urgent issues, such as the fact that large parts of Earth are becoming uninhabitable. In my view, this Easter, Passover or Ramadan is the perfect time to start.

I’m a political scientist who studies how religious groups respond to problems, from environmental crises to domestic violence to racism. Since 2013, I have worked with other researchers, some religious and some not, to explore climate science with communities of faith.

I’ve seen the power of this approach: some 1,200 institutions have committed to divest from fossil-fuel companies, totalling US$14.5 trillion (£10.5 trillion). One-third are faith-based organizations. Many, such as Operation Noah, are led by scientists. Similarly, the group Extinction Rebellion Muslims has built a transnational network with scientists and activists in Kenya, Gambia, the United Kingdom and beyond; they host ‘Green Ramadan’ seminars. Their efforts stalled plans for a luxury tourist resort that would have destroyed parts of the Nairobi National Park in Kenya. A co-campaigner, Maasai leader Nkamunu Patita, has been appointed to a government task force that will map wildlife-migration routes and be consulted in future development plans.

This is the opening of an opinion piece published in Nature on 30 March 2021. This is open access and can be read in full here.

Dr Tobias Müller is a Junior Research Fellow at the Woolf Institute and an Affiliated Lecturer at Cambridge’s Department of Politics and International Studies (POLIS).

Earth has experienced five major extinction events over the last 500 million years, the fifth and most recent responsible for wiping out the dinosaurs 66 million years ago. Massive volcanic eruptions have been identified as a major driver in the environmental change which triggered at least three of these extinctions.

But what dealt the final blow to the dinosaurs – whether an enormous outpouring of lava from the Deccan Traps volcanic province in India or a large asteroid impact or perhaps a combination of the two – has remained open to debate.

Now, a multi-institutional research team, led by scientists from the City University of New York (CUNY), and involving the University of Cambridge, has, for the first time, accurately pinpointed the timing and amount of carbon released from Deccan Traps volcanic province. The new data means scientists can now assess the role of volcanism in climate shifts around the End-Cretaceous mass extinction.

The team’s data show that CO₂ outgassing from Deccan Traps magmas can explain a warming of Earth’s global temperatures by roughly 3 degrees Celsius during the early phases of Deccan volcanism, but shows that the warming had lessened by the time of the mass extinction event.

Their findings support the theory that later Deccan magmas were not releasing that much CO₂, suggesting that volcanic carbon emissions didn’t play a major role in the dinosaur’s extinction.

“The results are important because they show that major volcanic events can release substantial amounts of CO₂ not just from surface vents, but also from the large and complex plumbing systems that feed them. Even though volcanic carbon emissions alone couldn’t have triggered the mass extinction, our data highlights their influence on our planet’s climate and habitability,” said co-author Professor Sally Gibson, from Cambridge’s Department of Earth Sciences.

The team had to search through hundreds of Deccan lava samples to identify suitable candidates to profile for their trapped CO₂ content. “In modern volcanic eruptions, such as the current one in Iceland, the CO₂ is trapped in crystals that are embedded in glassy fragments of rapidly cooled magma, but these are fragile and not preserved in the 65 million-year-old Deccan Traps,” said Gibson.

Recent research has identified a global warming event that occurred several hundred thousand years before the End-Cretaceous extinction. Some scientists have linked the eruption of the Deccan Traps to this warming event, but there is debate over whether the lavas that erupted could have released enough CO₂ into the atmosphere to cause it.  Adding to this mystery, the lava volumes that erupted during this time are relatively small compared to the volumes erupted during subsequent stages of Deccan Traps activity. A major challenge in this debate has been the lack of CO₂ data on Deccan magmas from this time.

“The new data highlights that carbon outgassing from lava volumes alone couldn’t have caused that level of global warming. But, when we factored in outgassing from magmas that froze beneath the surface rather than erupting, we found that the Deccan Traps could have released enough CO₂ to explain this warming event,” said lead-author Andres Hernandez Nava, a PhD student in The Graduate Center, CUNY Earth.

For their study, the team used lasers and beams of ions to measure the amount of CO₂ inside tiny droplets of frozen magma trapped inside Deccan Traps crystals from the End Cretaceous time period. They also measured the amounts of other elements, such as barium and niobium, which are indicators for how much CO₂ the magmas started out with. Finally, they performed modeling of latest Cretaceous climate to test the impacts of Deccan Traps carbon release on surface temperatures.

“Our lack of insight into the carbon released by magmas during some of Earth’s largest volcanic eruptions has been a critical gap for pinning down the role of volcanic activity in shaping Earth’s past climate and extinction events,” said Black, the study’s principal investigator and a professor in the Earth and Environmental Science program at The Graduate Center CUNY and City College of New York. “This work brings us closer to understanding the role of magmas in fundamentally shaping our planet’s climate, and specifically helps us test the contributions of volcanism and the asteroid impact in the end-Cretaceous mass extinction.”

Reference:
Hernandez Nava et al. Reconciling early Deccan Traps CO2 outgassing and pre-KPB global climate. PNAS (2021). DOI : 10.1073/pnas.2007797118

Adapted from a press release by The Graduate Center, CUNY.

The clinical trial – named HEAL-COVID – also aims to cut the number of patients being readmitted to hospital with complications as a result of having COVID.

Data from the Office for National Statistics suggests that 29% of patients who are hospitalised due to COVID-19 are readmitted within six months, and more than 12% die within the same period.

HEAL-COVID stands for Helping to Alleviate the Longer-term consequences of COVID-19 and is funded by the National Institute for Health Research (NIHR) and the NIHR Cambridge Biomedical Research Centre. It will test a number of safe, existing drugs on patients across the UK in order to find effective treatments.

Study lead Dr Charlotte Summers, from the University of Cambridge and Addenbrooke’s Hospital, said: “Having survived the trauma of being hospitalised with COVID-19, far too many patients find themselves back in hospital with new or long-term complications.

“Unfortunately, many go on to die in the months after being discharged. This trial is the first of its kind to look at what drugs we could use to reduce the devastating impact on patients.”

The trial is being led by Cambridge University Hospitals NHS Foundation Trust and University of Cambridge, in collaboration with Liverpool Clinical Trials Centre at the University of Liverpool, and Aparito Limited.

HEAL-COVID will enrol patients when they are discharged from hospital, following their first admission for COVID-19.  They will be randomised and given one of two drugs – apixaban and atorvastatin – and their progress tracked. It’s hoped a third drug will be introduced to the trial on the recommendation of the UK COVID Therapeutic Advisory Panel in the coming weeks.

Prof Carrol Gamble, Director of the Liverpool Clinical Trials Centre, said: “This is an exciting opportunity to help people in the post-acute phase of COVID-19. The trial is designed to allow us to remove or add-in treatment options in response to patient outcomes. Every effort has been made to design the trial to minimise burden on NHS staff and patients and represents a true team approach to science.”

NHS medical director, Professor Stephen Powis, said: “The NHS led the world in research identifying dexamethasone as the first treatment in the world for COVID-19 and this latest trial could help discover new treatments for the after-effects of COVID, helping to rapidly get world-leading therapies to our patients.

“Long COVID can have a significant impact on someone’s quality of life, which is exactly why in addition to funding research into the condition, the NHS has invested millions into opening dozens of dedicated clinics to help people get back to good health.”

Lord Bethell, Minister for Innovation, said:  “The UK is a world-leader in developing life-saving treatments in response to the pandemic and this clinical trial is further evidence of this. It is vital we continue our search for the best treatments for COVID-19, particularly to prevent people developing long-term complications after becoming ill.

“Clinical trials platforms like HEAL are showing how innovative designs can mean we can reach just the right candidates, quickly and emphatically. I am massively grateful to the incredible scientists and clinicians at Cambridge University who are driving forward this life-saving work, which will play a critical role in putting this pandemic behind us.”

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

Black and Chinese pupils were 26% and 38% more likely to be autistic respectively and autistic children were much more likely to face significant social disadvantage. The results are published today in JAMA Pediatrics.

The team drew on data from the School Census from the National Pupil Database, collected by the Department for Education from individuals aged 2-21 years old in state-funded schools in England. Of more than 7 million pupils studied, 119,821 pupils had a diagnosis of autism in their record in the English state educational system, of whom 21,660 also had learning difficulties (18.1%). Boys showed a prevalence of autism of 2.8% and girls showed a prevalence of 0.65%, with a boy-to-girl ratio of 4.3:1.

Prevalence was highest in pupils of black ethnicity (2.1%) and lowest in Roma/Irish Travellers (0.85%), with these estimates being the first to be published for these populations. Pupils with a record of autism in schools were 60% more likely to also be socially disadvantaged, and 36% less likely to speak English. The findings reveal significant differences in autism prevalence, as recorded in formal school systems, across ethnic groups and geographical location.

The lead researcher of the study, Dr Andres Roman-Urrestarazu from the Autism Research Centre (ARC) and Cambridge Public Health at the University of Cambridge, said: “We can now see that autism is much more common than previously thought. We also found significant variations in autism diagnosis in different ethnic minorities, though the reason why this should be the case isn’t clear and warrants further research.”

Previous estimates of the prevalence of autism in the UK by the same research group in Cambridge, and based on a school-based survey, suggested that one in 64 children (1.57%) were autistic. The new study, based on school records that usually underestimate the actual proportion of children who meet diagnostic criteria, shows a considerable increase in the autism prevalence in England. The researchers say the increase is likely to be because autism has become better recognised by both parents and schools in recent years.

Professor Carol Brayne, Co-chair of Cambridge Public Health and Professor of Public Health Medicine, said: “This study shows how we can draw on large datasets in a way that is rigorous and valuable for our understanding of autism.”

Professor Fiona Matthews from Newcastle University added: “This study highlights the need for more attention to the unrecognised and differing needs of autistic children from disadvantaged and diverse backgrounds.”

Professor Simon Baron-Cohen, Director of the ARC, said: “We can now see a snapshot of how many autistic children there are, and can drill down into local and ethnic variation, and reveal links with vulnerability. It is important that we safeguard the rights of children to access diagnostic services and education, tailored to their needs.”

This research was made possible by a generous donation for a Global Public Health Leadership programme by Dennis and Mireille Gillings Fellowship awarded to Dr Andres Roman-Urrestarazu. This study was also supported by the Autism Research Trust, the Wellcome Trust, the Innovative Medicines Initiative 2 Joint Undertaking (JU), the NIHR Cambridge Biomedical Research Centre and the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust.

Reference
Roman-Urrestarazu, R et al. Association of Race/Ethnicity and Social Disadvantage With Autism Prevalence in 7 Million School Children in England.  JAMA Pediatrics; 29 March 2021; DOI: 10.1001/jamapediatrics.2021.0054

Despite widespread optimism that educational technology, or ‘EdTech’, can help to level the playing field for young people with disabilities, the study found a significant shortage of evidence about which innovations are best-positioned to help which children, and why; specifically in low-income contexts.

The review also found that many teachers lack training on how to use new technology, or are reluctant to do so.

The study was carried out for the EdTech Hub partnership, by researchers from the Universities of Cambridge, Glasgow and York. They conducted a detailed search for publications reporting trials or evaluations about how EdTech is being used to help primary school-age children with disabilities in low- and middle-income countries. Despite screening 20,000 documents, they found just 51 relevant papers from the past 14 years – few of which assessed any impact on children’s learning outcomes.

Their report describes the paucity of evidence as ‘astonishing’, given the importance of educational technologies to support the learning of children with disabilities. According to the Inclusive Education Initiative, as many as half the estimated 65 million school-age children with disabilities worldwide were out of school even before the COVID-19 pandemic, and most face ongoing, significant barriers to attending or participating in education.

EdTech is widely seen as having the potential to reverse this trend, and numerous devices have been developed to support the education of young people with disabilities. The study itself identifies a kaleidoscopic range of devices to support low vision, sign language programmes, mobile apps which teach braille, and computer screen readers.

It also suggests, however, that there have been very few systematic attempts to test the effectiveness of these devices. Dr Paul Lynch, from the School of Education, University of Glasgow, said: “The evidence for EdTech’s potential to support learners with disabilities is worryingly thin. Even though we commonly hear of interesting innovations taking place across the globe, these are not being rigorously evaluated or documented.”

Professor Nidhi Singal, from the Faculty of Education, University of Cambridge, said: “There is an urgent need to know which technology works best for children with disabilities, where, and in response to which specific needs. The lack of evidence is a serious problem if we want EdTech to fulfil its potential to improve children’s access to learning, and to increase their independence and agency as they progress through school.”

The report identifies numerous ‘glaring omissions’ in the evaluations that researchers did manage to uncover. Around half were for devices designed to support children with hearing or vision difficulties; hardly any addressed the learning needs of children with autism, dyslexia, or physical disabilities. Most were from trials in Asia or Africa, while South America was underrepresented.

Much of the evidence also concerned EdTech projects which Dr Gill Francis, from the University of York and a co-author, described as ‘in their infancy’. Most focused on whether children liked the tools, or found them easy to use, rather than whether they actually improved curriculum delivery, learner participation and outcomes. Attention was also rarely given to whether the devices could be scaled up – for example, in remote and rural areas where resources such as electricity are often lacking. Few studies appeared to have taken into account the views or experiences of parents or carers, or of learners themselves.

The studies reviewed also suggest that many teachers lack experience with educational technology. For example, one study in Nigeria found that teachers lacked experience of assistive technologies for students with a range of disabilities. Another, undertaken at 10 schools for the blind in Delhi, found that the uptake of modern low-vision devices was extremely limited, because teachers were unaware of their benefits.

Despite the shortage of information overall, the study did uncover some clear evidence about how technology – particularly portable devices – is transforming opportunities for children with disabilities. Deaf and hard-of-hearing pupils, for instance, are increasingly using SMS and social media to access information about lessons and communicate with peers; while visually-impaired pupils have been able to use tablet computers, in particular, to magnify and read learning materials.

Based on this, the report recommends that efforts to support children with disabilities in low- and middle-income countries should focus on the provision of mobile and portable devices, and that strategies should be put in place to ensure that these are sustainable and affordable for parents and schools – as cost was another concern that emerged from the studies cited.

Critically, however, the report states that more structured evidence-gathering is urgently needed to ensure EdTech meets the UN’s stated goal to ‘ensure inclusive and equitable quality education and promote lifelong learning for all’. The authors suggest that there is a need to adopt more robust research designs, which should address a full range of disabilities, and involve pupils, carers and teachers in the process.

“There is no one-size-fits-all solution when working with children with disabilities,” Singal added. “That is why the current lack of substantive evidence is such a concern. It needs to be addressed so that teachers, parents and learners are enabled to make informed judgements about which technological interventions work, and what might work best for them.”

Researchers discovered changes to 12 genetic regions in the DNA of people who have had a lacunar stroke – a type of stroke caused by weakening of the small blood vessels deep within the brain. Over time, damage to the blood vessels and subsequent interruption to blood flow can lead to long-term disability, causing difficulty with thinking, memory, walking and ultimately dementia.

There are few proven drugs to prevent or treat lacunar strokes. The blood vessels affected are less than a millimetre wide and a lacunar stroke can strike without the person knowing. It’s not usually until someone has had a number of these strokes and starts to see signs of dementia that they realise something is wrong.

To date, only one genetic fault has been associated with lacunar strokes. However, after over a decade of research, Professor Hugh Markus and his team at the University of Cambridge working with researchers from around the world now believe their genetic breakthrough holds the key to finding much-needed treatments for lacunar stroke and vascular dementia.

In research funded by the British Heart Foundation, the team scanned and compared the genetic code of 7,338 patients who had a lacunar stroke with 254,798 people who had not. Participants were recruited from across Europe, United States, South America and Australia after they attended hospital and had an MRI or CT brain scan.

They discovered that many of the 12 genetic regions linked to lacunar strokes were involved in maintaining the neurovascular unit – the part of the brain that separates the blood vessels from the brain and ensures that nerves function normally. These genetic changes are thought to make the small blood vessels ‘leakier’, causing toxic substances to enter the brain, and meaning that messages travelling around the brain slow down or don’t arrive at all.

The team now plan to test whether new treatments can correct these abnormalities on brain cells in the lab. They hope to begin human clinical trials in the next ten years.

The study also highlighted that high blood pressure, type 2 diabetes and a history of smoking are causally associated with an increased risk of lacunar stroke, identifying things that we can immediately tackle.

Professor Hugh Markus, leader of the study and neurologist at the University of Cambridge, said: “These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to. Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

Dr Matthew Traylor, first author of the study at Queen Mary University of London, said: “Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said:

“This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35,000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the

Reference

Traylor, M et al. Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies. Lancet Neurology; 26 Mar 2021. 

Adapted from a press release by the British Heart Foundation

The Kennel Club Charitable Trust has funded the centre since its initial launch at the Animal Health Trust in 2009. The new centre will continue to be led by Dr Cathryn Mellersh, and will resume its mission to develop DNA tests and breeding tools for some of the most common and debilitating inherited conditions in dogs.

Professor James Wood, Head of the Department of Veterinary Medicine at the University of Cambridge, said: “We are delighted that the important work by Cathryn and her team, funded by The Kennel Club Charitable Trust, can now continue through the Canine Genetics Centre at Cambridge Vet School. We look forward to working together for the health and welfare of our much loved canines.”

The Kennel Club and the canine genetics team will work together to ensure that the centre’s research targets conditions that have the greatest impact on the health of dogs. The Kennel Club’s breed health and conservation plans, a project that gathers all available health information and data about each breed, will play a vital role in guiding the centre’s objectives and areas of research.

During its time at the Animal Health Trust, The Kennel Club Canine Genetics Centre had a significant impact on the health of numerous breeds. Researchers at the centre developed 25 different DNA tests for canine inherited diseases that affect over 50 breeds. Research into the impact of some of these tests revealed that over a ten year period, thanks to uptake of these tests by responsible breeders, the frequency of disease-causing genetic variants in some breeds reduced by a staggering 90%.

Close collaboration with breed clubs and breeders is essential to the success of the centre, as is the collection of over 40,000 DNA samples that has been developed over the last 20 years. These samples, along with valuable scientific and DNA sequence data, have now been secured and transferred to the University of Cambridge for further analysis.

Dr Cathryn Mellersh, head of The Kennel Club Genetics Centre said: “The last ten years have been incredibly important to dog health and, thanks to the University of Cambridge, especially Professor James Wood for all his assistance in safeguarding our resources and The Kennel Club Charitable Trust, this work can now continue. Our work to support breeders in reducing health problems in dogs is essential and we are eager to continue this important work and are thankful to everyone for their support.”

Further information regarding The Kennel Club’s extensive work in the field of canine health and research can be found on The Kennel Club website.

Adapted from a press release by The Kennel Club.

Results from the LHCb Collaboration at CERN suggests particles are not behaving the way they should according to the guiding theory of particle physics – suggesting gaps in our understanding of the Universe.

Physicists from the Universities of Cambridge, Bristol, and Imperial College London led the analysis of the data to produce this result, with funding from the Science and Technology Facilities Council. The result – which has not yet been peer-reviewed – was announced today at the Moriond Electroweak Physics conference and published as a preprint.

Beyond the Standard Model

Scientists across the world will be paying close attention to this announcement as it hints at the existence of new particles not explained by the Standard Model.

The Standard Model is the current best theory of particle physics, describing all the known fundamental particles that make up our Universe and the forces that they interact with. However, the Standard Model cannot explain some of the deepest mysteries in modern physics, including what dark matter is made of and the imbalance of matter and antimatter in the Universe.

Dr Mitesh Patel of Imperial College London, and one of the leading physicists behind the measurement, said: “We were actually shaking when we first looked at the results, we were that excited. Our hearts did beat a bit faster.

“It’s too early to say if this genuinely is a deviation from the Standard Model but the potential implications are such that these results are the most exciting thing I’ve done in 20 years in the field. It has been a long journey to get here.”

Building blocks of nature

Today’s results were produced by the LHCb experiment, one of four huge particle detectors at CERN’s Large Hadron Collider (LHC).

The LHC is the world’s largest and most powerful particle collider – it accelerates subatomic particles to almost the speed of light, before smashing them into each other.

These collisions produces a burst of new particles, which physicists then record and study in order to better understand the basic building blocks of nature.

The LHCb experiment is designed to study particles called ‘beauty quarks’, an exotic type of fundamental particle not usually found in nature but produced in huge numbers at the LHC.

Once the beauty quarks are produced in the collision, they should then decay in a certain way, but the LHCb team now has evidence to suggest these quarks decay in a way not explained by the Standard Model.

Questioning the laws of physics

The updated measurement could question the laws of nature that treat electrons and their heavier cousins, muons, identically, except for small differences due to their different masses.

According to the Standard Model, muons and electrons interact with all forces in the same way, so beauty quarks created at LHCb should decay into muons just as often as they do to electrons.

But these new measurements suggest this is not happening.

One way these decays could be happening at different rates is if never-before-seen particles were involved in the decay and tipped the scales in favour of electrons.

Dr Paula Alvarez Cartelle from Cambridge’s Cavendish Laboratory, was one of the leaders of the team that found the result, said: “This new result offers tantalising hints of the presence of a new fundamental particle or force that interacts differently with these different types of particles.

“The more data we have, the stronger this result has become. This measurement is the most significant in a series of LHCb results from the past decade that all seem to line up – and could all point towards a common explanation.

“The results have not changed, but their uncertainties have shrunk, increasing our ability to see possible differences with the Standard Model.”

Not a foregone conclusion

In particle physics, the gold standard for discovery is five standard deviations – which means there is a 1 in 3.5 million chance of the result being a fluke. This result is three deviations – meaning there is still a 1 in 1000 chance that the measurement is a statistical coincidence.

It is therefore too soon to make any firm conclusions. However, while they are still cautious, the team members are nevertheless excited by this apparent deviation and its potentially far-reaching implications.

The LHCb scientists say there has been a breadcrumb trail of clues leading up to this result – with a number of other, less significant results over the past seven years also challenging the Standard Model in a similar way, though with less certainty.

If this result is what scientists think it is – and hope it is – there may be a whole new area of physics to be explored.

Dr Konstantinos Petridis of the University of Bristol, who also played a lead role in the measurement, said: “The discovery of a new force in nature is the holy grail of particle physics. Our current understanding of the constituents of the Universe falls remarkably short – we do not know what 95% of the Universe is made of or why there is such a large imbalance between matter and anti-matter.

“The discovery of a new fundamental force or particle, as hinted at by the evidence of differences in these measurements could provide the breakthrough required to start to answer these fundamental questions.”

Dr Harry Cliff, LHCb Outreach Co-Convener, from Cambridge’s Cavendish Laboratory, said: “This result is sure to set physicists’ hearts beating a little faster today. We’re in for a terrifically exciting few years as we try to figure out whether we’ve finally caught a glimpse of something altogether new.”

It is now for the LHCb collaboration to further verify their results by collating and analysing more data, to see if the evidence for some new phenomena remains.

Additional information – about the result

The results compare the decay rates of Beauty mesons into final states with electrons with those into muons.

The LHCb experiment is one of the four large experiments at the Large Hadron Collider (LHC) at CERN in Geneva, and is designed to study decays of particles containing a beauty quark

This is the quark with the highest mass forming bound states. The resulting precision measurements of matter-antimatter differences and rare decays of particles containing a beauty quark allow sensitive tests of the Standard Model of particle physics.

Rather than flying out in all directions, beauty quarks that are created in the collisions of the proton beams at LHC stay close to the beam pipe.

The UK team studied a large number of beauty or b quarks decaying into a strange-quark and two oppositely charged leptons. By measuring how often the b-quark decays into a final state containing a pair of muons or a pair of electrons, they found evidence that the laws of physics might be different, depending on whether the final state contains electrons or muons.

Since the b-quark is heavy compared to the masses of the electron and muon it is expected that the b-quark decays with the same probability into a final state with electrons and muons. The ratio between the two decay probabilities is hence predicted to be one.

However analysis of the UK team found evidence that the decay probability is less than one.

If the trial is successful, it may pave the way for a new treatment to prevent or alleviate the impact of COVID-19 in people on dialysis, people who have had a kidney transplant, and people with auto-immune diseases affecting the kidneys such as vasculitis who require treatment to suppress their immune system. The treatment will last up to nine months.

Led by scientists from the Cambridge University Hospitals NHS Trust and the University of Cambridge, the PROphylaxis for vulnerable paTiEnts at risk of COVID-19 infecTion (PROTECT-V) trial will start in Cambridge with a plan to expand to other UK healthcare centres. It will recruit at least 1,500 kidney patients, who will be randomised to receive either a placebo (or dummy) drug, or UNI911 (niclosamide) as a nasal spray, both provided by the manufacturer UNION therapeutics, in addition to all their usual treatments. Participants can receive the vaccine and still take part in this trial, which will identify whether niclosamide can protect people from the virus either on its own, or in combination with any of the vaccines currently available.

Niclosamide has been re-formulated into a nasal spray so it can be delivered directly to the lining of the nasal cavity, like a hayfever spray. In the trial, people will take one puff up each nostril twice a day, as this is the part of the body where the virus can take hold. This ‘local’ drug delivery is likely to reduce the chances of people experiencing any side effects.

Usually used to treat intestinal worms and taken as a tablet, niclosamide has shown real promise in the lab. Early tests revealed niclosamide could stop SARS-CoV-2 multiplying and entering cells of the upper airways.

Dr Rona Smith, senior research associate at the University of Cambridge and honorary consultant nephrologist at Addenbrooke’s Hospital, who is leading the UK study, said: “It is vital that we find a way to protect patients on haemodialysis and other high-risk kidney patients from catching SARS-CoV-2 and developing COVID-19. If they get it, they are more likely to fall seriously ill or die, and we need to find a way to change that.

“We believe testing niclosamide is particularly important for people who are immunosuppressed and have kidney disease, because their immune responses to vaccines can sometimes be less effective. While the vaccine will offer a level of protection, niclosamide may provide further protection against COVID-19 that doesn’t rely on the immune system mounting a response.

“If successful, our innovative trial could mean that the treatment becomes available to kidney patients more widely within months. It would mean they could receive their regular life-saving dialysis or take their immunosuppressant drugs without additional worry. And if it’s successful it could even be rolled out more widely – and benefit more vulnerable people.”

The trial involves researchers and patients from across the UK. It is funded by LifeArc, Kidney Research UK, the Addenbrooke’s Charitable Trust and UNION therapeutics and is supported by the NIHR Cambridge Biomedical Research Centre. UNION therapeutics is supplying the drug.

Professor Jeremy Hughes, kidney doctor and chair of trustees at Kidney Research UK, said: “Sadly, one in five kidney patients receiving dialysis in hospital or who have a kidney transplant and tested positive for the virus died within four weeks. Many of those on dialysis are having to put themselves at risk and attend their renal unit for life-saving dialysis treatment several times each week. And those who have had a kidney transplant must continue taking their immunosuppressant drugs, despite these making them more susceptible to infection.”

“Repurposing already available drugs or those in the late stage of development offers the fastest route to bring benefit to patients at this critical time,” said Melanie Lee, CEO of LifeArc.

Announcing the PROTECT-V trial, Matt Hancock, Health and Social Care Secretary, said: “Since the beginning of the pandemic, we have worked to find the best treatments the world has to offer for COVID-19.

“We have been clear from the outset that it will be a combination of safe and effective vaccines, testing and therapeutics that will bring an end to this pandemic, and we will not rest until every individual in the country is protected against this awful disease.”

Kidney patients who would like to take part in the PROTECT-V trial should speak to their nephrologist in their local centre to find out if their centre is participating in the trial and if they are eligible to take part.

Adapted from a press release by Kidney Research UK.

Professor Guillén will officially begin his role as Director on 1 September 2021, succeeding Professor Christoph Loch, who has been Director of the School since 2011.

Professor Guillén has taught at the Wharton School since 1996 and was the Anthony L Davis Director of the Joseph H Lauder Institute of Management & International Studies from 2007-2019, leading its first-ever fundraising campaign and launching a new curriculum emphasising hands-on learning experiences. He has long been a champion of diversity.

He has furthered the sociological study of the global system, and advanced comparative research on institutions, artistic movements, organisations, business groups, multinational firms, and digital platforms. His scholarship has received numerous distinctions, including Fulbright and Guggenheim fellowships, the Aspen Institute’s Faculty Pioneer Award, the President’s Book Award of the Social Science History Association, and a membership in the Institute for Advanced Study, Princeton.

Professor Guillén is also a bestselling author, including the recently published “2030: How Today’s Biggest Trends Will Collide and Reshape the Future of Everything.”

“Professor Mauro Guillén is ideally placed to build on the great work carried out by Professor Christoph Loch and his predecessors. Mauro is a distinguished academic of the highest calibre. His commitment to academic excellence, diversity, and innovation in teaching will ensure Cambridge Judge Business School continues to excel in its next phase of development and growth”, says Professor Stephen J Toope, Vice-Chancellor of the University of Cambridge. “I am delighted that Mauro will be joining us and very much look forward to working with him.”

“I am thrilled to become Director of Cambridge Judge Business School, at the University of Cambridge, and to further its educational and research mission”, says Professor Guillén.

During the decade Professor Loch served as Cambridge Judge Director, the School strengthened its degree and Executive Education programmes, and boosted its research quality with a strategy that emphasises innovation and impact over quantity. The result of this was reflected in an improvement in global programme rankings as well as the School’s standing in the UK’s Research Excellence Framework (REF) and other indicators.  Over the course of this time, the School doubled in revenues, contributed to the University, and maintained a strong financial position.

The School’s faculty and research centres now engage with global companies and other organisations in areas ranging from restructuring hospitals for better health outcomes, to creating machine-readable financial regulation, to developing cybersecurity policies. Cambridge Judge faculty and mentors guide companies varying from tech startups to social enterprises on their journey from idea to team building to scaling up for growth.

New degree programmes launched during Professor Loch’s tenure include Masters degrees in Social Innovation, Entrepreneurship and Accounting, while new research centres now address such issues as alternative finance, strategic philanthropy, leadership gender diversity and the circular economy. Cambridge Judge has also transformed itself physically: the new 5,000m² Simon Sainsbury Centre opened to students and Executive Education delegates in 2018, greatly expanding the School’s lecture, meeting and dining facilities while uniting Cambridge Judge activities under one roof.

Originally published on the Cambridge Judge Business School website.

The six-session programme involves providing carefully-prepared feedback to parents about how they can build on positive moments when playing and engaging with their child using video clips of everyday interactions, which are filmed by a health professional while visiting their home.

It was trialled with 300 families of children who had shown early signs of behaviour problems. Half of the families received the programme alongside routine healthcare support, while the other half received routine support alone. When assessed five months later, the children whose families had access to the video-feedback approach displayed significantly reduced behavioural problems compared with those whose families had not.

All of the children were aged just one or two: far younger than the age at which interventions for behaviour problems are normally available. The results suggest that providing tailored support for parents at this earlier stage, if their children show early signs of challenging behaviour – such as very frequent or intense tantrums, or aggressive behaviour – would significantly reduce the chances of those problems worsening.

Children with enduring behaviour problems often experience many other difficulties as they grow up: with physical and mental health, education, and relationships. Behaviour problems currently affect 5% to 10% of all children.

The trial – one of the first ever ‘real-world’ tests of an intervention for challenging behaviours in children who are so young – was carried out by health professionals at six NHS Trusts in England and funded by the National Institute for Health Research. It was part of a wider project called ‘Healthy Start, Happy Start’, which is testing the video-based approach, led by academics at the University of Cambridge and Imperial College London.

Dr Christine O’Farrelly, from the Centre for Play in Education, Development and Learning (PEDAL), Faculty of Education, University of Cambridge, said: “Often, as soon as you move a programme like this to a real health service setting, you would expect to see a voltage drop in its effectiveness compared with research conditions. Instead, we saw a clear and striking change in child behaviour.”

Beth Barker, a research assistant at the PEDAL Centre, said: “The fact that this programme was effective with children aged just one or two represents a real opportunity to intervene early and protect against enduring mental health problems. The earlier we can support them, the better we can do at improving their outcomes as they progress through childhood and into adult life.”

The programme, known as the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), is delivered across six home visits, each lasting about 90 minutes.

Health professionals film the family in everyday situations – such as playing together, or having a meal – and then analyse the content in depth. During the next visit, they review specific clips, highlighting often fleeting moments when the parents and child appear to be ‘in tune’. They discuss what made these successful, as well as any incidents in which more challenging issues arose. This helps the parents to identify particular cues and signals from their children and respond in a manner that helps their children feel understood and reinforces positive engagement and behaviours.

The 300 participating families all had children who scored within the top 20% for behaviour problems during standard healthcare assessments. Misbehaviour is a normal part of toddlerhood, and not all of the children would necessarily have gone on to develop serious problems. All were, however, deemed ‘at-risk’ because they exhibited challenging behaviours like tantrums and rule-breaking more severely and frequently than most. These are often the early symptoms of disruptive behaviour disorders and typically emerge at 12 to 36 months.

The researchers used various tools, principally interviews with the parents, to assess each child’s behaviour before the trial, and again five months after. Each child received a score based on the frequency and severity of challenging behaviours including tantrums, ‘destructive’ behaviours (such as deliberately breaking a toy or spilling a drink); resisting rules and requests; and aggressive behaviour (hitting or biting).

Between the assessments, all 300 families received the routine healthcare available to them for early symptoms of behaviour problems. The researchers describe this as ‘typically minimal’, as there is currently no standard pathway of support for behaviour problems in such young children. Only half of the families were given access to the parenting programme.

In the second assessment, five months later, children from families who received the extra video feedback support scored significantly lower for all measures of behaviour problems than those who only received routine care.

The average difference between the scores of the two groups was 2.03 points. While the exact meaning of this varied depending on the specific problems exhibited by the child, the researchers describe it as roughly equivalent to the difference between having tantrums every day, and having tantrums once or twice a week. Similarly, in the case of destructive behaviours, it represents the disparity between regularly throwing or breaking toys and other items, and barely doing so at all.

Encouragingly, 95% of the participants persevered with the trial to its conclusion, suggesting that most families are able to accommodate the visits.

Paul Ramchandani, Professor of Play in Education, Development and Learning at the University of Cambridge, said: “To provide this programme in any health service would require investment, but it can realistically be delivered as part of routine care. Doing so would benefit a group of children who are at risk of going on to have problems with their education, behaviour, future wellbeing and mental health. There is a chance here to invest early and alleviate those difficulties now, potentially preventing problems in the longer term that are far worse.”

The results are reported in JAMA Pediatrics. The Healthy Start, Happy Start project is also reviewing further data from the project – including assessments of the children two years after the trial – which will be reported at a later date.