An army of cells constantly patrols within us, attacking anything it recognises as foreign, keeping us safe from invading pathogens. But sometimes things go wrong: the soldiers mistake benign cells for invaders, turning their friendly fire on
us and declaring war.

The consequences are diseases like multiple sclerosis (MS), asthma, inflammatory bowel disease, type 1 diabetes and rheumatoid arthritis – diseases that are increasing at an alarming rate in both the developed and developing worlds.

Cambridge will be ramping up the fight against immune-mediated and inflammatory diseases with the opening next year of the Cambridge Institute of Therapeutic Immunology and Infectious Disease, headed by Professor Ken Smith. The Institute will work at the interface between immunity, infection and the microbiome (the microorganisms that live naturally within us). “We’re interested in discovering fundamental mechanisms that can turn the immune system on or off in different contexts, to modify, treat or prevent both inflammatory and infectious diseases,” says Smith.

But while diseases such as Crohn’s and asthma have long been understood to be a consequence of friendly fire, scientists are starting to see this phenomenon give rise to more surprising conditions, particularly in mental health.

In 2009, Professor Belinda Lennox, then at Cambridge and now at Oxford, led a study that showed that 7% of patients with psychoses tested positive for antibodies that attacked a particular receptor in the brain, the NMDA receptor. This blocked a key neurotransmitter, affecting communication between nerve cells and causing the symptoms.

Professor Alasdair Coles from Cambridge’s Department of Clinical Neurosciences is working with Lennox on a trial to identify patients with this particular antibody and reverse its effects. One of their treatments involves harnessing the immune system – weaponising it, one might say – to attack rogue warriors using rituximab, a monoclonal antibody therapy that kills off B-cells, the cells that generate antibodies.

“You can make monoclonal antibodies for experimental purposes against anything you like within a few days,” explains Coles. “In contrast, to come up with a small molecule – the alternative sort of drug – takes a long, long time.”

The first monoclonal antibody to be made into a drug, created here in Cambridge, is called alemtuzumab. It targets both B- and T-cells and has been used in a variety of autoimmune diseases and cancers. Its biggest use is in MS, where it eliminates the rogue T- and B-cells that attack the protective insulation (myelin sheath) around nerve fibres. Licensed in Europe in 2013 and approved by NICE in 2014, it has now been used in tens of thousands of MS patients.

As well as treating diseases caused by the immune system, antibody therapies are now widely used to treat cancer. And, as Professor Gillian Griffiths, Director of the Cambridge Institute for Medical Research, explains, antibody-producing cells are not the only immune cells that can be weaponised.

“T-cells are also showing great promise,” she says. “They are the body’s serial killers, patrolling, identifying and destroying infected and cancer cells with remarkable precision and efficiency.”

But cancer cells are able to trick T-cells by sending out a ‘don’t kill’ signal. Antibodies that block these signals, which have become known as ‘checkpoint inhibitors’, are proving remarkably successful in cancer therapies. “My lab focuses on what tells a T-cell to kill, and how you make it a really good killer, using imaging and genetic approaches to understand how these cells can be fine-tuned,” Griffiths explains. “This has revealed some novel mechanisms that play key roles in regulating killing.”

A second, more experimental, approach uses souped-up cells known as chimeric antigen receptor (CAR) T-cells programmed to recognise and attack a patient’s tumour.

Neither approach is perfect: antibody therapies can dampen down the entire immune system, causing secondary problems, while CAR T-cell therapies are prohibitively expensive as each CAR T-cell needs to be programmed to suit an individual. But, says Griffiths, “the results to date from both approaches are really rather remarkable”.

One of the problems that’s dogged immunotherapy trials is that T-cells only have a short lifespan. Most of the T-cells transplanted during immunotherapy are gone within three days, nowhere near long enough to defeat the tumour.

This is where Professor Randall Johnson comes in. He’s been working with a molecule (2-hydroxyglutarate), which he says has “become trendy of late”. It’s an ‘oncometabolite’, believed to be responsible for making cells cancerous, which is why pharmaceutical companies are trying to inhibit its action. Johnson has taken the opposite approach.

He’s shown that a slightly different form of the molecule plays a critical role in T-cell function: it can turn them into renewable cells that hang around for a long time and can reactivate to combat cancer. Increasing the levels of this molecule in T-cells makes them stay around longer and be much better at destroying tumours. “Rather than creating killer T-cells that are active from the start, but burn out very quickly, we’re creating an army of cells that can stay quiet for a long time, but will go into action when necessary.”

This counterintuitive approach caught the attention of Apollo Therapeutics, who recognised the enormous promise and has invested in Johnson’s work, which he carried out in mice, to see if it can be applied to humans.

But T-cells face other problems, particularly in pancreatic cancer, explains Professor Duncan Jodrell from the Cancer Research UK Cambridge Institute, which is why immunotherapy against these tumours has so far failed. The problem with pancreatic cancer is that ‘islands’ of tumour cells sit in a ‘sea’ of other material, known as stroma. As Jodrell and colleagues have shown, it’s possible for T-cells to get into the stroma, but they go no further. “You can rev up your T-cells, but they just can’t get at the tumour cells.” They are running a study that tries to overcome this immune privilege and allow the T-cells to get to the tumour cells and attack them.

Tim Eisen, Professor of Medical Oncology at Cambridge and Head of the Oncology Translational Medicine Unit at AstraZeneca, believes we can expect great advances in cancer treatment from optimising and, in some cases, combining existing checkpoint inhibitor approaches.

Eisen is working with the Medical Research Council to trial checkpoint inhibitor antibody therapies as a complement – ‘adjuvant’ – to surgery for kidney cancer. Once the kidney is removed, the drug is used to destroy stray tumour cells that have remained behind. But even antibody therapies, which are now widely used within the NHS, are not universally effective and can cause serious complications. “One of the most important things for us to focus on now is which immunotherapeutic drug or particular combination of drugs might be effective in destroying tumour cells and be well tolerated by the patient.”

T-cell therapies – and, in particular, CAR T-cell therapies – are “very exciting, futuristic and experimental,” he says, “but they’re going to take some years to come in as standard therapy.”

The problem is how to make them cost-effective. “It’s never going to be easier to engineer an individual person’s T-cells than it is to take a drug off the shelf and give it to them,” he says. “The key is going to be whether you can industrialise production. But I’m very optimistic about our ability to re-engineer processes and make it available for people in general.”

We may soon see an era, then, when our immune systems become an unstoppable force for good.

The researchers, from the University of Cambridge, used data from the Sloan Digital Sky Survey and computer simulations to demonstrate that these stellar sprinters originated in the Large Magellanic Cloud (LMC), a dwarf galaxy in orbit around the Milky Way.

These fast-moving stars, known as hypervelocity stars, were able to escape their original home when the explosion of one star in a binary system caused the other to fly off with such speed that it was able to escape the gravity of the LMC and get absorbed into the Milky Way. The results are published in the Monthly Notices of the Royal Astronomical Society, and will be presented today (5 July) at the National Astronomy Meeting in Hull.

Astronomers first thought that the hypervelocity stars, which are large blue stars, may have been expelled from the centre of the Milky Way by a supermassive black hole. Other scenarios involving disintegrating dwarf galaxies or chaotic star clusters can also account for the speeds of these stars but all three mechanisms fail to explain why they are only found in a certain part of the sky.

To date, roughly 20 hypervelocity stars have been observed, mostly in the northern hemisphere, although it’s possible that there are many more that can only be observed in the southern hemisphere.

“Earlier explanations for the origin of hypervelocity stars did not satisfy me,” said Douglas Boubert, a PhD student at Cambridge’s Institute of Astronomy and the paper’s lead author. “The hypervelocity stars are mostly found in the Leo and Sextans constellations – we wondered why that is the case.”

An alternative explanation to the origin of hypervelocity stars is that they are runaways from a binary system. In binary star systems, the closer the two stars are, the faster they orbit one another. If one star explodes as a supernova, it can break up the binary and the remaining star flies off at the speed it was orbiting. The escaping star is known as a runaway. Runaway stars originating in the Milky Way are not fast enough to be hypervelocity because blue stars can’t orbit close enough without the two stars merging. But a fast-moving galaxy could give rise to these speedy stars.

The LMC is the largest and fastest of the dozens of dwarf galaxies in orbit around the Milky Way. It only has 10% of the mass of the Milky Way, and so the fastest runaways born in this dwarf galaxy can easily escape its gravity. The LMC flies around the Milky Way at 400 kilometres per second and, like a bullet fired from a moving train, the speed of these runaway stars is the velocity they were ejected at plus the velocity of the LMC. This is fast enough for them to be the hypervelocity stars.

“These stars have just jumped from an express train – no wonder they’re fast,” said co-author Rob Izzard, a Rutherford fellow at the Institute of Astronomy. “This also explains their position in the sky, because the fastest runaways are ejected along the orbit of the LMC towards the constellations of Leo and Sextans.”

The researchers used a combination of data from the Sloan Digital Sky Survey and computer simulations to model how hypervelocity stars might escape the LMC and end up in the Milky Way. The researchers simulated the birth and death of stars in the LMC over the past two billion years, and noted down every runaway star. The orbit of the runaway stars after they were kicked out of the LMC was then followed in a second simulation that included the gravity of the LMC and the Milky Way. These simulations allow the researchers to predict where on the sky we would expect to find runaway stars from the LMC.

“We are the first to simulate the ejection of runaway stars from the LMC – we predict that there are 10,000 runaways spread across the sky,” said Boubert. Half of the simulated stars which escape the LMC are fast enough to escape the gravity of the Milky Way, making them hypervelocity stars. If the previously known hypervelocity stars are runaway stars it would also explain their position in the sky.

Massive blue stars end their lives by collapsing to a neutron star or black hole after hundreds of millions of years and runaway stars are no different. Most of the runaway stars in the simulation died ‘in flight’ after being kicked out of the LMC. The neutron stars and black holes that are left behind just continue on their way and so, along with the 10,000 runaway stars, the researchers also predict a million runaway neutron stars and black holes flying through the Milky Way.

“We’ll know soon enough whether we’re right,” said Boubert. “The European Space Agency’s Gaia satellite will report data on billions of stars next year, and there should be a trail of hypervelocity stars across the sky between the Leo and Sextans constellations in the North and the LMC in the South.”

Reference
D. Boubert, D. Erkal, N. W. Evans and R. G. Izzard. ‘Hypervelocity runaways from the Large Magellanic Cloud.’ Monthly Notices of the Royal Astronomical Society (2017). DOI: 10.1093/mnras/stex848.

Tomorrow, tens of thousands of people will descend on London to celebrate Pride, the annual march through the streets of the city to celebrate lesbians, gays, people who are bisexual and transgender and those who belong to other sexual minorities – the LGBT+ community.

Where last year’s parade was swelled by people marching in solidarity with those tragically killed in the terrible shooting at Orlando earlier that month, this year’s may well be boosted by a positive celebration: fifty years since the decriminalisation of gay sex.

Anyone old enough to remember this point in history, or even the eighties, when the spectre of AIDS hung over the gay community and the Thatcher government introduced Section 28 to prohibit local authorities from "promoting" homosexuality, will realise how far we have come since then. In 2017 the rights of our LGBT friends in our community are protected in law, and same sex marriage is broadly accepted.

But while I don’t want to rain on everyone’s parade, we – LGBT and straight alike – shouldn’t be too complacent. There is still a lot of work to be done.

Last week, the charity Stonewall, which campaigns for equality for LGBT people in all walks of life, published a report looking at the experiences of LGBT pupils at our schools. The research behind this report was led by Dr Vasanti Jadva from Cambridge’s Centre for Family Research and was a follow up to its two previous studies, published in 2007 and 2012.

The findings of the study give us cautious optimism – but I want to stress that word, cautious. Compared to the previous studies, it found that pupils at our schools encounter less bullying based on their sexual or gender identity, are less likely to hear casual homophobic language such as “faggot” or “lezza” and are more likely to be taught about LGBT issues at school. But that does not mean that these problems have gone away.  And for one group in particular – those pupils who define themselves as transgender – their experiences are far from positive.

More than 3,700 LGBT young people aged 11-19 across Britain took part in the study, completing an online questionnaire asking about their experiences at school, online and at home.

The top line finding of this important report is very positive: homophobic and biphobic bullying has fallen by a third over ten years. But this masks the fact that 45% of our pupils are still bullied because they are LGBT. And if you are trans, more likely than not you will have been bullied – 64% of trans pupils report being bullied. Even more horrifying, nearly one in ten trans pupils have been subjected to death threats at school.

Half of LGBT pupils frequently hear homophobic language at school. The phrase “that’s so gay” – used infamously by DJ Chris Moyles during his spell on Radio 1 – is still used very commonly, with 86% of pupils regularly hearing this or similar phrases at school.

What happens when teachers witness the bullying or hear such offensive language at school? Not enough, it seems. Fewer than a third of LGBT pupils say their teachers intervened when they were present during the bullying, and seven in ten say teachers only ‘sometimes’ or ‘never’ challenge homophobic, biphobic or transphobic language when they hear it.

There have been improvements, though: the number of schools that tell their pupils homophobic bullying is wrong is up from a shameful 25% when our researchers first did their study to 68% this time round. Faith schools are most likely to let their pupils down – just 57% tell their pupils that homophobic bullying is wrong, and only 29% tell them transphobic bullying is wrong.

Schools are more likely to teach their pupils about LGBT issues now, too. In 2007, 70% of pupils had never been taught about such matters, but this is down to 40% now. But again, if you’re trans, your experience is much worse – three in four LGBT pupils have never learnt about gender identity and what ‘trans’ means at schools (and in fact, this is a similar figure for bisexuality).

We know that positive role models can help pupils as they grow up, and it’s perhaps a reflection of the changing environment in which gays and lesbians can marry and are more visible that means that 27% of LGBT pupils known of an openly gay member of staff and 22% of an openly lesbian member of staff. But the stigma surrounding bisexuality and transgender is reflected in that only a tiny minority know staff in these groups (4% and 3% respectively).

So what does all this mean for a pupil’s development? We know that mental health issues among young people are becoming an increasing concern, and this is particularly reflected among LGBT pupils. An alarming 61% of LGBT pupils have deliberately harmed themselves, and more than one in five (22%) have attempted to take their own lives, a figure barely changed since 2012. This is just not acceptable.

Stonewall has rightly used the findings of the report to make a number of recommendations to improve the experiences of LGBT pupils across the country. Ruth Hunt, chief executive of Stonewall, described the report as “a wake-up call for schools, government and politicians on just how far we still have to go."

While some of the recommendations are aimed at ensuring that staff are empowered to offer appropriate support to their LGBT pupils, many are aimed at showing their pupils that it’s okay to be LGBT. If this report tells us one thing, it’s the importance of allowing people to celebrate who they are, no matter their sexuality or gender identity. It’s what we strive for at Cambridge, to be a university to which any student can aspire to come and not only engage in great scholarship, but to also be free, happy, and proud of their individuality and sexuality.

The Stonewall report encourages us to celebrate difference and make the diversity of LGBT people visible. This is what Pride is all about – and you can see the impact it can have by listening to those who have been fortunate enough to attend. Lauren, a 16 year old pupil in the East Midlands, who contributed to the study put it so clearly when saying that: “After I went to Pride, I felt much more confident and able to come out because of how well bisexuality was accepted there. Going to Pride helped me to gain confidence in myself and to come out.”

So go out there tomorrow, enjoy yourself. Be proud. And let our children and teenagers see that they, too, have so much to be proud about.

If you are an LGBT+ young person in or around looking for help and support, you can contact The Kite Trust, which offers free support for LGBT+ people under the age of 25.

The opinions expressed in this article are those of the individual author and do not represent the views of the University of Cambridge.

Kidneys perform a number of vital functions, including filtering waste and toxins out of the blood, producing vitamin D, and regulating blood pressure. The filtration function of the kidneys is measured by the glomerular filtration rate (GFR), the rate at which blood is passed through the glomeruli, the small blood vessel filters in the kidneys.

Determination of the GFR is important because the assessment of kidney function can indicate how a disease is progressing, whether a drug treatment is having adverse side-effects on key bodily functions, and if it is safe to prescribe a drug at a certain dose, a question of particular importance to cancer doctors when prescribing chemotherapy drugs. However, measuring GFR is technically difficult. Doctors therefore often rely on ways to estimate GFR, which can be relatively inaccurate.

“Almost every patient with cancer gets a measurement of their kidney function, reported as estimated GFR, and this value influences many treatment decisions, but until now, we did not know the best way to provide this value for patients with cancer,” says Dr Tobias Janowitz from the Cancer Research UK (CRUK) Cambridge Institute at the University of Cambridge, joint first author. “Given how important this measure is in day-to-day clinical practice, we felt that we should provide an evidence-based model for its calculation in this context.”

Now, in a study published today in the Journal of Clinical Oncology, the authors describe a new and better way to estimate the GFR, which has been developed using data from a large dataset of over 2,500 patients. They used accurate measurements of GFR to provide a gold standard and then statistical modelling methods to find the best mathematical model to estimate GFR. The new model also provides a measure of the uncertainty for this estimate.

To test the use of this revised method of estimating GFR, the researchers focused on the precision of chemotherapy dosing, specifically dosing of carboplatin, which is used to treat multiple cancers, such as lung cancer, germ cell tumours, ovarian cancer, and breast cancer. The new model reduced the probability of incorrect dosing for carboplatin substantially compared to the current models used in clinical practice, from more than 20% for the currently published models to 11.7% with the new model.

“Accuracy in chemotherapy dosing is very important,” says Edward Williams, joint first author, also from the CRUK Cambridge Institute. “Too much chemotherapy can be toxic and can even be life threatening, but too little chemotherapy may be ineffective against the cancer. Our model should help doctors calculate chemotherapy doses more accurately and thereby reduce the risk of toxicity or treatment failure.”

The model has been made available for clinicians to access online free of charge.

“We believe this tool, which is based on stringent methodology, could have a positive impact on the care for a great many patients with cancer,” says senior author Professor Helena Earl from the Department of Oncology at Cambridge. “This is why we have made it free and easily accessible.”

“The limitation of our work that we are most aware of is that due to the patient demographics in our data set, our model does not provide guidance on the impact of race on the estimated GFR, though it is well known that race can be a key variable,” explains Dr Janowitz. “This will be addressed in future work. We are also keen to explore how well the new model performs for patients with diseases other than cancers.

“The work is a very good example of scientists from different specialties coming together to provide an advance for the care that we offer to patients with cancer.”

The study was supported by Cancer Research UK, the Wellcome Trust, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Chemotherapy drugs are very powerful, so having the correct dose makes an enormous difference to how effective they are and how we can avoid unnecessary side effects.  This way of measuring how well a patient’s kidneys are working and how quickly chemotherapy drugs like carboplatin leave the body helps to make our treatments more accurate and better suited to each individual.”

Reference
Janowitz, J et al. A new model for estimating glomerular filtration rate in patients with cancer. Journal of Clinical Oncology; 7 July 2017; DOI: 10.1200/JCO.2017.72.7578

Huntington’s disease affects more than 6,700 people in the UK. It is an incurable neurodegenerative disease. It is typically an adult-onset disease, although there is a juvenile form. Initially, the disease affects motor coordination, mood, personality and memory, but then leads to difficulty in speech and swallowing, loss of motor function and death at a relatively early age. There is no known cure for the disease, only ways to manage the symptoms.

The disease is caused by a mutation in the genetic code in the huntingtin (HTT) gene. Genetic information is coded in DNA that is made up of a repeated string of four molecules known as nucleotides, or bases – A, C, G and T. The HTT gene contains a repeated string of CAG bases: in healthy individuals, the CAG repeat is around 20 CAGs long, but if the repeat has 36 or more CAGs, an individual will develop Huntington’s disease.

The Huntington’s disease sheep were developed in 2006 by a team led by Professor Sir Richard Faull and Professor Russell Snell from the University of Auckland, New Zealand. Together with colleagues in Australia, they successfully bred a strain of Merino sheep carrying the human genetic mutation that causes Huntington's disease in patients. While mice and rats are used in the vast majority of disease studies in the UK, the sheep is an important new animal model for Huntington’s disease. Not only do sheep live much longer than rodents, but also sheep brains are larger and closer in size and structure to humans.

The Cambridge research will be led by Professor Jenny Morton from the Department of Physiology, Development and Neuroscience. “Even though we’ve known for decades now exactly which genetic mutation causes Huntington’s disease, we’re arguably still no nearer a cure – the best we can do is manage the symptoms,” she says.  “Even those treatments are limited to some of the motor symptoms.”

The sheep model is particularly important, because until recently, scientists have been unable to model the disease in longer-living animals. This matters because the symptoms of Huntington’s rarely appear before adulthood; sheep can live for at least 10-12 years, which gives a much wider window of opportunity for studying the disease than is possible in mice.

“It has taken our collaborators in Australia years of research to develop these sheep, but we’re already beginning to get insights into how the disease progresses, particularly before symptoms become apparent,” says Professor Morton.

The Huntington’s disease sheep are already proving their value. Although even up to the age of nine years they look completely normal, the researchers have observed some interesting progressive behavioural changes. In addition, a study led by Professor Morton published earlier this year in Scientific Reports used the Huntington’s disease sheep in Australia to identify early biomarkers of disease: changes in metabolites in blood taken from sheep at a pre-symptomatic stage of the disease showed that Huntington’s disease affects important metabolic processes in the body prior to the appearance of physical symptoms.

Until 2014, it was not possible to import live sheep from Australia to the UK. However, changes in regulations allowed Professor Morton to import the Huntington’s disease sheep. The first sheep were imported earlier this year, but have only just been released from quarantine.

“We have done many experiments using the sheep in Australia over the past seven years, and we will continue to use them there,” says Professor Morton. “However, we cannot do some of the more technically demanding experiments, or behavioural studies that take a long time, on field trips. We have excellent animal facilities in Cambridge and so are in a good position to do the long term behavioural monitoring that will help us understand how the neurological symptoms develop.”

The imported sheep will be used to study brain and behavioural changes that cause Huntington’s disease, with a particular emphasis on understanding the cognitive decline. Professor Morton has developed a number of tests that can be used for measuring learning and memory in sheep. These have been based on the tests used for monitoring symptom progression in patients with Huntington’s disease. By using tests similar to those used in patients, she hopes that the findings from the sheep studies can be ‘translated’ directly back to humans. Once they have the basic measures established, they will begin testing novel therapies in the Huntington’s disease sheep.

“These sheep will be invaluable to us in our search for a better understanding of Huntington’s disease, so we are grateful to the authorities for allowing them to be imported,” says Professor Morton. “We hope in future to be able to breed these sheep here, rather than having to import them, but we know that even getting to the stage of breeding them in Australia has been a challenge for the team there.”

Each year an estimated 1.03 million people around the world, many of them in poor countries, contract leptospirosis, with 58,900 of these infections resulting in death. Better known as Weil’s disease, leptospirosis is spread by animals such as rats and transmitted to humans when they come into contact with food, water or soil that is contaminated by infected animal urine. The infection can be successfully treated if diagnosed early. Untreated, the disease can lead to death.

Diagnosis of leptospirosis presents problems: the infection shares symptoms with other diseases, including dengue, malaria and viral hepatitis. The only way to confirm the illness is to take a blood sample and run specialised diagnostic tests. This process can be time-consuming and expensive.

Now, a global collaboration between Cambridge University and University of Ghana researchers in biotechnology, pathology and manufacturing is bringing a cheap diagnostic test a step closer.

The global project was made possible through the Royal Society’s Global Challenge Research Fund, which enables outstanding UK research leaders to develop international collaborations with the best leading researchers from around the world, to work on some of the global challenges and problems facing developing countries.

Lead researchers Professor Elizabeth (Lisa) Hall (Head of the Cambridge Analytical Biotechnology Group) and Dr Gordon Awandare (Director of the West African Centre for Cell Biology of Infectious Pathogens) are also working with engineers such as Dr Ronan Daly (IfM, Department of Engineering) to manufacture a single instrument, similar to the home pregnancy test, which will deliver accurate and rapid point-of-care diagnosis.

“Health practitioners need a simple test that enables them to detect the difference between bacterial and viral infections – such as leptospirosis and dengue – because they require very different treatments,” says Professor Hall.

“Our target is to develop a diagnostic test requiring a blood sample from a finger prick at a cost of less than $0.50 per test. The test has the potential to transform the way we diagnose and treat the one million people who contract leptospirosis every year.”

One of the most expensive components of the test for leptospirosis is the enzyme used to amplify the pathogen’s genetic material (DNA/RNA) to high enough levels to be detected.

“Specialist skills and refrigeration are required in traditional manufacturing of the enzyme,” says Professor Hall. “To overcome these barriers to local production, we’ve developed a technique that allows for direct purification of the enzyme from cell culture and packages it ready for use.”

The team is also developing a novel technique to extract the pathogen’s DNA/RNA directly from the blood sample. “Both the DNA/RNA extraction system and the enzyme will be contained on a diagnostic card that can be manufactured locally – and ultimately from local materials,” says Professor Hall.

International cooperation has been crucial in the development of the test (see panel below). The Cambridge scientists are also working with Universiti Putra Malaysia – and would welcome new partners, both in the UK and overseas.

“We hope to deliver a sustained improvement in healthcare while also developing local economies. Local fabrication will drive sustainable local enterprise and help improve technological education,” says Dr Daly. “Leptospirosis has been recognised as a neglected disease by the World Health Organization and there is scope for taking a similar approach for developing point-of-care diagnostic tests for other treatable infectious diseases.

“They include food and waterborne diseases (bacterial diarrhoea, enteric fever, hepatitis A), vector-borne diseases (malaria, dengue, chikungunya and Zika), zoonotic diseases (leptospirosis, rabies) respiratory infections (influenza-like illnesses, pneumonia, tuberculosis) and HIV infection. These patients present with fever and a wide range of non-specific symptoms, which are difficult to diagnose without specialist laboratory tests. These may be expensive and/or unavailable, resulting in presumptive diagnosis and empirical treatment, which may be unnecessary, incorrect or potentially even harmful.”

The various elements of the test are currently being developed in the lab, with the first protoype expected to be produced in 2018.

The programme, called Designing Our Tomorrow, was founded by researchers at the University of Cambridge, and brings real-world problems into classroom design and technology sessions in secondary schools, and encouraging the next generation of UK designers and engineers.

As part of their classroom curriculum, students from different secondary schools have been learning about what makes an effective and useful design. Their goal was to design a type of packaging which would contain everything a young child with asthma would need, whether they’re at home, at school or elsewhere; and one which would help reduce anxiety of children with asthma by using child-friendly design themes. “In other words, we want to make it fun,” said Ian Hosking of Cambridge’s Department of Engineering, who co-leads the Designing Our Tomorrow (DOT) programme, in collaboration with the Faculty of Education. “We want to re-frame what education can be – projects like these start to form a broader evidence base of what’s possible.”

Five of the best designs were presented by students from Wimbledon High School GDST at the British Paediatric Respiratory Society conference last Friday (30 June) in Cambridge.

Students were not merely designing packaging but an experience. Themes included a monkey character where the inhaler and spacer become a banana that the child can ‘feed’ the monkey with and then copy themselves. Other themes include a pack shaped like a cat where the inhalers become mice that are stored in a smaller box shaped like a wedge of cheese; and a folding pack that can hang on a door for easy access at home but can be quickly zipped up and put in a bag to take out.

“Seeing how people were scared of asthma…this affects and could benefit a lot of people. The child wanted it to be fun, the gran wanted emergency instructions, the parents wanted it to be compact and small and the nurse wanted it to be organised – so we took all of that and designed our packs,” said Charlotte, aged 11 from Wimbledon High.

Several of the designs have been made into initial corrugated cardboard prototypes by UK packaging company DS Smith, with the aim of piloting them in partnership with the NHS in London through the Healthy London Partnership.

“It has been great doing something which is able to change and improve children’s lives and help them get better,” said Sascha, aged 12 from Wimbledon High, one of the students who presented her design at the conference. “I am so happy and glad that they have decided to take mine to the next stage and it could appear in people’s homes.”

Asthma affects one in 11 children in the UK. On average, there are three children with asthma in every classroom in the UK, and a child is admitted to hospital every 20 minutes due to an asthma attack.

This DOT project has focused specifically on asthma in children under six years of age. It addresses the anxiety that a child feels in the early stages of treatment and the co-ordination of the equipment and their instructions to help ensure compliance with their treatment plan.

“DOT is a fascinating project which aims to bring real-world problems into classroom design and technology sessions in secondary schools,” said Sara Nelson from the Healthy London Partnership. “It’s one of the more rewarding pieces of work that I have had the pleasure of being involved in during the last year, the one I have learned the most from, and it involved collaborating with an unusual partner for the NHS.”

Each of the students was given all of the tools which a child with asthma or their carer would need to manage their condition, including inhalers, spacers, and emergency instructions. Through a set of classroom lessons, the students’ way of thinking was developed in order to help them understand how to be creative by breaking fixation through the use of stimulus.

Fixation is a common problem in design – for example, if you’re trying to design a new type of chair and all you’re shown are other chairs, you’ll just end up designing a variant of what already exists. “If I want to design a new chair, the last thing I should look at is a chair,” said Bill Nicholl from Cambridge’s Faculty of Education, who co-leads the DOT programme.

“Children and young people are terribly creative, and the NHS should involve them more in co-designing what we do,” said Nelson. “We should not be afraid to put our heads above the parapet and should look outside the NHS to what partnerships might be out there to help us solve some of our tricky problems – I know that we can learn an awful lot from engineers.”

The students from Wimbledon High also gained valuable industry experience working with DS Smith, who will help refine the students’ concepts into something that can be manufactured in large volumes. “By working with industry, it takes the project beyond a competition to something that can make a difference to patients and help prevent avoidable asthma deaths in children,” said Hosking. 

“This project has shown yet again the potential of young people and their ability to engage with, and ultimately solve, complex design problems. We underestimate their creativity at our peril. Solving real problems like this should be at the heart of all young people’s educational experiences,” said Nicholl.

Wimbledon High Head of Design & Technology Marcia Phillip has been deeply involved in the project: “It puts authentic challenges and engineering practice at the heart of the learning experience and this appealed to me, particularly working in a girls’ school. We know there is a shortage of engineers in the UK – particularly women – and I thought we should get our girls inspired from an early age. The girls have been highly engaged and excited – after all, they are playing a part in the University of Cambridge’s research and their ideas will potentially be implemented within the NHS.”

“I feel like I am doing something for a purpose and it makes me feel happy that I am helping people,” said Charlotte. “I feel accomplished and proud of what I have done because it was a long process but it was all worth it.”

DOT is funded in part by engineering design consultants Peter Brett Associates and ARM Ltd.

The two-day conference (July 13-14) at Jesus College is the first major event held by the Leverhulme Centre for the Future of Intelligence (CFI) since its globally-publicised launch by Stephen Hawking and other AI luminaries in October 2016.

Bringing together policy makers and philosophers, as well as leading figures from science and technology, speakers include Astronomer Royal Martin Rees, Matt Hancock (Minister for Digital and Culture), Baroness Onora O'Neill and Francesca Rossi (IBM).

Dr Stephen Cave, Executive Director of CFI, said: “Rarely has a technology arrived with such a rich history of myth, storytelling and hype as AI. The first day of our conference will ask how films, literature and the arts generally have shaped our expectations, fears and even the technology itself.

“Meanwhile, the second day will ask how and when we can trust the intelligent machines on which we increasingly depend – and whether those machines are changing how we trust each other."

Programme highlights of the conference include:

• Sci-Fi Dreams: How visions of the future are shaping development of intelligent technology
• Truth Through Fiction: How the arts and media help us explore the challenges and opportunities of AI
• Metal people: How we perceive intelligent robots – and why
• Trust, Security and the Law: Assuring safety in the age of artificial intelligence
• Trust and Understanding: Uncertainty, complexity and the ‘black box’

Professor Huw Price, Academic Director of the Centre, and Bertrand Russell Professor of Philosophy at Cambridge, said: “During two packed days in Cambridge we’ll be bringing together some of the world’s most important voices in the study and development of the technologies on which all our futures will depend.

“Intelligent machines offer huge benefits in many fields, but we will only realise these benefits if we know we can trust them – and maintain trust in each other and our institutions as AI transforms the world around us.”

Other conference speakers include Berkeley AI pioneer Professor Stuart Russell, academic and broadcaster Dr Sarah Dillon, and Sir David Spiegelhalter, Cambridge’s Winton Professor of the Public Understanding of Risk. An AI-themed art exhibition is also being held to coincide with the Jesus College event.

CFI brings together four of the world’s foremost universities (Cambridge, Berkeley, Imperial College and Oxford) to explore the implications of AI for human civilisation. Researchers will work with policy-makers and industry to investigate topics such as the regulation of autonomous weaponry, and the implications of AI for democracy.

Many researchers take seriously the possibility that intelligence equal to our own will be created in computers within this century. Freed of biological constraints, such as limited memory and slow biochemical processing speeds, machines may eventually become more broadly intelligent than we are – with profound implications for us all.

Launching the £10m centre last year, Professor Hawking said: “Success in creating AI could be the biggest event in the history of civilisation but it could also be the last – unless we learn how to avoid the risks. Alongside the benefits, AI will also bring dangers like powerful autonomous weapons or new ways for the few to oppress the many.

“We cannot predict what might be achieved when our own minds are amplified by AI. The rise of powerful AI will either be the best or the worst thing to happen to humanity. We do not yet know which.”

Professor Maggie Boden, External Advisor to the Centre, whose pioneering work on AI has been translated into 20 languages, said: “The practical solutions of AI can help us to tackle important social problems and advance the science of mind and life in fundamental ways. But it has limitations which could present grave dangers. CFI aims to guide the development of AI in human-friendly ways.”

Dr Cave added: “We've chosen the topic of myths and trust for our first annual conference because they cut across so many of the challenges and opportunities raised by AI. As well as world-leading experts, we hope to bring together a wide range of perspectives to discuss these topics, including from industry, policy and the arts. The challenge of transitioning to a world shared with intelligent machines is one that we all face together.”

The first day of the conference is in partnership with the Royal Society, while the second is in partnership with Jesus College's Intellectual Forum. The conference is being generously sponsored by Accenture and PwC.

Further details and ticketing information can be found here.

The European Atomic Energy Community (Euratom) has become a focal point for the Brexit debate in the UK. The UK’s departure from this organisation does not simply raise important questions about the future supply and use of radioactive materials in hospitals. It also dramatises wider debates about the need for transitional arrangements when the withdrawal negotiations are completed, and whether the UK’s ‘Article 50’ withdrawal letter can be revoked.

The United Kingdom is withdrawing not just from the treaties that establish the European Union, but also the 1957 treaty establishing the European Atomic Energy Community (Euratom). Euratom provides the legal framework for the European nuclear energy industry on issues like the handling of nuclear waste and the decommissioning of nuclear power plants, as well as promoting international cooperation on nuclear issues with the USA, Canada and Japan. But Euratom also regulates the wider use of radioactive materials, including their use by the medical profession for the diagnosis and treatment of medical conditions such as cancer.

Although Euratom is governed by a separate treaty, it is EU institutions and EU agencies that provide the administrative and judicial framework for its application and enforcement.

In her March ‘Article 50’ letter to European Council President, Donald Tusk, the Prime Minister Theresa May notified the EU of the UK’s intention to withdraw not just from the treaties establishing the EU, but also from Euratom. That leaves open not just the issue of how the nuclear industry will be regulated in the UK in the future, but also how European and international cooperation for the safe movement, supply and use of radioactive material will be secured. Understandably, some worry about the UK leaving the EU without an appropriate replacement legal framework in place and there have been calls from different quarters for transitional arrangements to be in place. Rather late in the day, there now seems to be an acceptance within government that transitional frameworks will be needed to secure an orderly Brexit.

Yet for some Brexit supporters, the risk of a transitional framework is that it might be a way of avoiding Brexit, or at least prolonging the jurisdiction of the European Court of Justice –a ‘red line’ for many. It is worth noting that the Court has delivered only a handful of rulings involving Euratom and the UK, relating primarily to its implementation of directives to protect workers against exposure to radiation. After Brexit, regulation and enforcement activities will be transferred to national institutions.

However, there have been calls for the UK to remain within Euratom, with the UK Parliament set to debate the issue on 12 July. The problem is that the UK has already notified its intention to withdraw from the Euratom Treaty. Any attempt to remain in Euratom would beg the question whether the Article 50 letter can be subsequently amended or indeed, revoked.

The wording of Article 50 does not tell us whether amendment or revocation is possible. A European Commission Press Release does state that notification is a ‘point of no return’ and does not provide for ‘unilateral withdrawal of notification’. This is simply the opinion of the Commission and has no binding legal quality. Only the Court of Justice can decide this question. And there is legal opinion which considers that notification is open to revocation, including without the consent of the other EU governments.

The important point is that if it is possible for the UK to change its mind on Euratom, it can change its mind on Brexit. The same Article 50 process applies to both. But beyond the legal questions, the difficulties thrown up by withdrawal from Euratom are not any different from those of leaving the EU more generally. The debate about leaving Euratom may become a catalyst for a wider reflection on the real costs and benefits of Brexit.

Kenneth Armstrong’s book, Brexit Time – Leaving the EU: Why, How and When? published by Cambridge University Press is out now.

Why did life on Earth change from small to large when it did? Researchers from the University of Cambridge and the Tokyo Institute of Technology have determined how some of the first large organisms, known as rangeomorphs, were able to grow up to two metres in height, by changing their body size and shape as they extracted nutrients from their surrounding environment.

The results, reported in the journal Nature Ecology and Evolution, could also help explain how life on Earth, which once consisted only of microscopic organisms, changed so that huge organisms like dinosaurs and blue whales could ultimately evolve.

Rangeomorphs were some of the earliest large organisms on Earth, existing during a time when most other forms of life were microscopic in size. Some rangeomorphs were only a few centimetres in height, while others were up to two metres tall.

These organisms were ocean dwellers that lived during the Ediacaran period, between 635 and 541 million years ago. Their soft bodies were made up of branches, each with many smaller side branches, forming a geometric shape known as a fractal, which can be seen today in things like lungs, ferns and snowflakes.

Since rangeomorphs don’t resemble any modern organism, it’s difficult to understand how they fed, grew or reproduced, let alone how they might link with any modern group. However, although they look somewhat like plants, scientists believe that they may have been some of the earliest animals to live on Earth.

“What we wanted to know is why these large organisms appeared at this particular point in Earth’s history,” said Dr Jennifer Hoyal Cuthill of Cambridge’s Department of Earth Sciences and Tokyo Tech’s Earth-Life Science Institute, the paper’s first author. “They show up in the fossil record with a bang, at very large size. We wondered, was this simply a coincidence or a direct result of changes in ocean chemistry?”

The researchers used micro-CT scanning, photographic measurements and mathematical and computer models to examine rangeomorph fossils from south-eastern Newfoundland, Canada, the UK and Australia.

Their analysis shows the earliest evidence for nutrient-dependent growth in the fossil record. All organisms need nutrients to survive and grow, but nutrients can also dictate body size and shape. This is known as ‘ecophenotypic plasticity.’ Hoyal Cuthill and her co-author Professor Simon Conway Morris suggest that rangeomorphs not only show a strong degree of ecophenotypic plasticity, but that this provided a crucial advantage in a dramatically changing world. For example, rangeomorphs could rapidly “shape-shift”, growing into a long, tapered shape if the seawater above them happened to have elevated levels of oxygen.

“During the Ediacaran, there seem to have been major changes in the Earth’s oceans, which may have triggered growth, so that life on Earth suddenly starts getting much bigger,” said Hoyal Cuthill. “It’s probably too early to conclude exactly which geochemical changes in the Ediacaran oceans were responsible for the shift to large body sizes, but there are strong contenders, especially increased oxygen, which animals need for respiration.”

This change in ocean chemistry followed a large-scale ice age known as the Gaskiers glaciation. When nutrient levels in the ocean were low, they appear to have kept body sizes small. But with a geologically sudden increase in oxygen or other nutrients, much larger body sizes become possible, even in organisms with the same genetic makeup. This means that the sudden appearance of rangeomorphs at large size could have been a direct result of major changes in climate and ocean chemistry.

However, while rangeomorphs were highly suited to their Ediacaran environment, conditions in the oceans continued to change and from about 541 million years ago the ‘Cambrian Explosion’ began – a period of rapid evolutionary development when most major animal groups first appeared in the fossil record. When the conditions changed, the rangeomorphs were doomed and nothing quite like them has been seen since.

Reference
Jennifer F. Hoyal Cuthill and Simon Conway Morris. ‘Nutrient-dependent growth underpinned the Ediacaran transition to large body size.’ Nature Ecology and Evolution (2017). DOI:10.1038/s41559-017-0222-7.

With the global population estimated to reach nine billion people by 2050, ensuring all people have access to sufficient food is one of this century’s greatest challenges.

Today, the Higher Education Funding Council for England (HEFCE) is announcing funding for the creation of a new Cambridge Centre for Crop Science (3CS) in collaboration with the National Institute of Agricultural Botany (NIAB). The new centre will provide a major boost to the University’s existing research initiatives around global food security. 

With £16.9m from the HEFCE-managed UK Research Partnership Investment Fund as well as some £14.5m from the NIAB Trust, the 3CS will focus on impact: working with industrial partners to translate the University’s strong fundamental plant research into outputs for the farmer, processor and consumer.

“3CS innovations will generate new crops and new ways of growing crops for food, fuels, industrial feedstocks and pharmaceuticals,” said Professor Sir David Baulcombe, head of Cambridge’s Department of Plant Sciences and the project lead for the University.

“We envisage that new 3CS crop technologies will enable higher crop yields and lower environmental impact for crop-based food production – as well as contributing to improved dietary health.”

The project leads say the 3CS will be uniquely well positioned to contribute to growth and innovation due to the partnership at its core: connecting the multidisciplinary research of the University with NIAB’s pipeline to the end-users in farming and food industries.   

“The delivery of both public goods and economic growth is an essential agenda for today’s plant scientists, with the need to produce sufficient healthy nutritious food without harming the environment being at the top of the international agenda,” said NIAB’s CEO and Director Dr Tina Barsby.

“Creating the facilities to bring together NIAB and the University in 3CS presents an extraordinary opportunity for impacting this agenda through the development of world-class science and translation.”

The funding from HEFCE will allow the 3CS to be housed in a state-of-the-art research laboratory at NIAB’s Cambridge site, where it will be led by a newly-appointed Professor of Crop Science. The Centre will involve researchers from Plant Sciences and other University departments, NIAB, the Cambridge Sainsbury Laboratory, and other UK and international research institutes.

3CS is already establishing connections with major industry partners, as well as agricultural supply chain networks such as the Cambridge University Potato Growers Research Association.

In addition to the Cambridge Centre, the funding will also provide new field stations and offices at NIAB’s Histon site, as well as new glasshouses with full environmental controls.

The Eastern region is a rich area for plant science, and benefits from the Agri-Tech East research and business network. 3CS will allow for closer collaboration with other regional institutes, including the John Innes Centre in Norwich and Rothamsted Research – both of whom have welcomed the establishment of the new centre.

Young researchers will be central to the success of 3CS, says Baulcombe, and the best will be recruited from around the world to be trained in interdisciplinary science, including the latest in plant genetics, bioinformatics, computational modelling and statistics.

Strong links with the agricultural industry through NIAB will mean that 3CS researchers will learn to understand how societal value and industry requirements feed into research design and translation.

While 3CS will make significant contributions to the main globally-traded crops such as wheat and rice, there will be a focus on advances in the genetics and agronomy of other UK crops, such as potato and legumes, and so-called ‘orphan crops’: those that lag behind in technological advances but are vital for smallholder farmers across the developing world.

Professor Sir Leszek Borysiewicz, the University’s Vice-Chancellor, said: “3CS will be unlike anywhere else in Europe because it connects a world-leading University directly to growers, breeders and other sectors of industry associated with crops. The opportunity could be compared to the potential for advances in healthcare when a research-active medical school co-locates with a hospital and pharmaceutical company.

“The 3CS will be the centrepiece of what will be significant new collaborations, and an exemplar of what can be achieved by bringing together interested parties to focus on sustainable crop production – essential for food security, resilience to climate change, and the growing bio-economy.”

A team of architects and chemists from the University of Cambridge has designed super-stretchy and strong fibres which are almost entirely composed of water, and could be used to make textiles, sensors and other materials. The fibres, which resemble miniature bungee cords as they can absorb large amounts of energy, are sustainable, non-toxic and can be made at room temperature.

This new method not only improves upon earlier methods of making synthetic spider silk, since it does not require high energy procedures or extensive use of harmful solvents, but it could substantially improve methods of making synthetic fibres of all kinds, since other types of synthetic fibres also rely on high-energy, toxic methods. The results are reported in the journal Proceedings of the National Academy of Sciences.

Spider silk is one of nature’s strongest materials, and scientists have been attempting to mimic its properties for a range of applications, with varying degrees of success. “We have yet to fully recreate the elegance with which spiders spin silk,” said co-author Dr Darshil Shah from Cambridge’s Department of Architecture.

The fibres designed by the Cambridge team are “spun” from a soupy material called a hydrogel, which is 98% water. The remaining 2% of the hydrogel is made of silica and cellulose, both naturally available materials, held together in a network by barrel-shaped molecular “handcuffs” known as cucurbiturils. The chemical interactions between the different components enable long fibres to be pulled from the gel.

The fibres are pulled from the hydrogel, forming long, extremely thin threads – a few millionths of a metre in diameter. After roughly 30 seconds, the water evaporates, leaving a fibre which is both strong and stretchy.

“Although our fibres are not as strong as the strongest spider silks, they can support stresses in the range of 100 to 150 megapascals, which is similar to other synthetic and natural silks,” said Shah. “However, our fibres are non-toxic and far less energy-intensive to make.”

The fibres are capable of self-assembly at room temperature, and are held together by supramolecular host-guest chemistry, which relies on forces other than covalent bonds, where atoms share electrons.

“When you look at these fibres, you can see a range of different forces holding them together at different scales,” said Yuchao Wu, a PhD student in Cambridge’s Department of Chemistry, and the paper’s lead author. “It’s like a hierarchy that results in a complex combination of properties.”

The strength of the fibres exceeds that of other synthetic fibres, such as cellulose-based viscose and artificial silks, as well as natural fibres such as human or animal hair.

In addition to its strength, the fibres also show very high damping capacity, meaning that they can absorb large amounts of energy, similar to a bungee cord. There are very few synthetic fibres which have this capacity, but high damping is one of the special characteristics of spider silk. The researchers found that the damping capacity in some cases even exceeded that of natural silks.

“We think that this method of making fibres could be a sustainable alternative to current manufacturing methods,” said Shah. The researchers plan to explore the chemistry of the fibres further, including making yarns and braided fibres.

This research is the result of a collaboration between the Melville Laboratory for Polymer Synthesis in the Department of Chemistry, led by Professor Oren Scherman; and the Centre for Natural Material Innovation in the Department of Architecture, led by Dr Michael Ramage. The two groups have a mutual interest in natural and nature-inspired materials, processes and their applications across different scales and disciplines.

The research is supported by the UK Engineering and Physical Sciences Research Council (EPSRC) and the Leverhulme Trust.

Reference
Yuchao Wu et al. ‘Bioinspired supramolecular fibers drawn from a multiphase self-assembled hydrogel.’ Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1705380114

The history of science is littered with self-experimenters so passionate about their work that they used themselves as human guinea pigs, however ill-advisedly.

Sir Joseph Barcroft (1872–1947) was one such character. Professor of Physiology at Cambridge, he was best known for his studies of the oxygenation of blood. He also led mountain expeditions where he analysed the oxygen content of his blood and that of other expedition members.

In the middle of his career, Barcroft built an airtight glass chamber in his laboratory in Cambridge. There, he could live and exercise at oxygen levels equivalent to 16,000 feet. Like many self-experimentation stories, things did not always go to plan: in one experiment, he had to be rescued by colleagues after spending six days in the chamber and reportedly turning blue.

Despite his occasional misguided venture, Barcroft’s scientific legacy was significant and so, in his honour, the University of Cambridge has recently opened a new state-of-the-art facility in his name. Research at the Barcroft Centre focuses on farm animals – mainly sheep and chickens, but also pigs – to model important aspects of human physiology.

The Centre’s work spans several areas including Professor Jenny Morton’s studies on understanding fatal neurodegenerative diseases such as Huntington’s disease and a similar childhood disease, Batten disease, and Dr Frances Henson’s work on bone diseases such as osteoarthritis.

However, a significant amount of its work focuses on how we develop in the womb and how this programmes us for increased risk of heart disease in later life. This seems fitting as, in later years, Barcroft became interested in fetal development, and in particular the effects of low levels of oxygen on the unborn baby in the womb.

Carrying on this legacy are Professor Dino Giussani and his postdocs Dr Kim Botting and Dr Youguo Niu. All are also members of the Centre for Trophoblast Research (CTR), which this year celebrates its tenth anniversary and focuses on the interactions between the pregnant mother and the fetus, as mediated by the placenta.

Low levels of oxygen – or hypoxia – can occur in high-altitude pregnancies. But, as Giussani explains, there are far more common causes. “Smoking, pre-eclampsia, even maternal obesity – these all increase the risk of hypoxia for the mother’s baby, as do inherited genetic variants,” he says.

Housed in the Barcroft Centre is a suite of hypoxia chambers – superficially similar, perhaps, to that in which Barcroft placed himself, but nowadays far more sophisticated (and much safer). These are not intended for humans, but rather for animals, each of which is very closely monitored, often remotely using technology developed by the team.

The smallest of these chambers doubles as an incubator for fertilised hens’ eggs. Scientists can watch the development of the fetus directly. They can see how the heart grows, for example, how it is affected by hypoxia, and what effect potential drugs have in ameliorating possible complications.

Of course, we grow in a womb, with a placenta connecting us to our mother and controlling our nutritional intake. Mice and rats are the most commonly used mammals in research, but to model mammalian development in longer-living species with similar rates of development to humans, it is necessary to turn to larger animals. Sheep make a good model. Not only is their gestation – and postnatal life – more comparable to a human’s than to a rat’s, but a newborn lamb’s physiology is also similar in a crucial way to a newborn baby’s: its heart is mature at birth. By comparison, a newborn rat’s heart is still very immature.

For part of gestation, the sheep are placed in hypoxia chambers, which contain finely controlled, lower-than-normal levels of oxygen. “This reduces the amount of oxygen in the blood of the pregnant sheep and thereby in her fetus,” explains Botting. “This mimics conditions where the placenta is not working appropriately, as in pregnancy complicated by pre-eclampsia or maternal obesity.”

The pregnant ewes deliver outside the chambers in normal ambient air. Once born, most of the lambs are put out to pasture in the paddocks adjacent to the Centre, where they grow to adulthood.

“The lambs which were hypoxic in the womb are not noticeably different,” says Giussani. “The sheep will effectively live a normal life. That is the very point, because underneath, a silent killer is brewing; we want to investigate what happens as they grow because there is a theory that a complicated pregnancy may increase the risk of heart disease in the offspring later in life.”

Professor Abby Fowden, Head of the School of the Biological Sciences, and another CTR member and user of the Barcroft Centre, says that the facilities are unique. “It’s probably the only centre in the UK that has the capacity – the surgical and care facilities – to do these kinds of long-term developmental and neurodegenerative studies,” she explains.

Like Giussani, Fowden and her collaborator Dr Alison Forhead are interested in how the early environment in the womb programmes us for disease in later life. They are particularly interested in the role of hormones – in both the mother and the fetus – and how they affect growth and development.

There are some conditions, such as hypothyroidism – whereby the body produces insufficient thyroid hormones – and maternal stress, that probably affect normal fetal development, but about which surprisingly little is understood. To model these conditions, Fowden and Forhead again turn to a range of mammals including sheep and pigs.

As Forhead explains, normal development of the fetus is crucial for health in later life. “In the case of many organs, you’re born with a certain number of functional units, and in postnatal life you don’t have the capacity to change that number. So the number you’re born with has long-lasting consequences.”

Take nephrons, for example. These are functional units of our kidneys that filter the blood and are responsible for how much salt and water is excreted into the urine. “If you’re born with fewer nephrons, this has consequences for how much salt you retain, setting you up in later life to be at greater risk of developing high blood pressure.”

What is apparent from this work is just how much of disease in later life is programmed in the womb. While our lifestyle – our diet, how much we exercise after birth – plays an important role in whether we develop heart disease or type 2 diabetes, for example, much of the risk is present before we are even born, programmed during pregnancy into how our DNA and tissues function.

And these effects don’t necessarily stop at the next generation, as Giussani is discovering in his parallel work with rodents, which allows two or more generations to be studied in a comparably short time.

“If we look at the ‘grandchildren’ of pregnant rats that had a hypoxic pregnancy, we see this disease risk being passed on again, but in a really interesting way,” he says. “A male ‘child’ passes on the cardiovascular risk to the ‘grandchild’, but female offspring confer protection. This is really exciting as inheritable protection against a future risk of heart disease has never been demonstrated in mammals.”

In other words, while we must still recognise our own contribution to our risk of developing certain diseases, some of this risk was programmed into us before we were born: in fact, even before our parents were born. Work at the Barcroft Centre – in monitoring animals for not just one generation but several – will be vital for understanding the consequences of pregnancy not only for our children but also for their children – and even their children’s children.

Inset image: Joseph Barcroft.
 

The smallest star yet measured has been discovered by a team of astronomers led by the University of Cambridge. With a size just a sliver larger than that of Saturn, the gravitational pull at its stellar surface is about 300 times stronger than what humans feel on Earth.

The star is likely as small as stars can possibly become, as it has just enough mass to enable the fusion of hydrogen nuclei into helium. If it were any smaller, the pressure at the centre of the star would no longer be sufficient to enable this process to take place. Hydrogen fusion is also what powers the Sun, and scientists are attempting to replicate it as a powerful energy source here on Earth.

These very small and dim stars are also the best possible candidates for detecting Earth-sized planets which can have liquid water on their surfaces, such as TRAPPIST-1, an ultracool dwarf surrounded by seven temperate Earth-sized worlds.

The newly-measured star, called EBLM J0555-57Ab, is located about six hundred light years away. It is part of a binary system, and was identified as it passed in front of its much larger companion, a method which is usually used to detect planets, not stars. Details will be published in the journal Astronomy & Astrophysics.

“Our discovery reveals how small stars can be,” said Alexander Boetticher, the lead author of the study, and a Master’s student at Cambridge’s Cavendish Laboratory and Institute of Astronomy. “Had this star formed with only a slightly lower mass, the fusion reaction of hydrogen in its core could not be sustained, and the star would instead have transformed into a brown dwarf.”

EBLM J0555-57Ab was identified by WASP, a planet-finding experiment run by the Universities of Keele, Warwick, Leicester and St Andrews. EBLM J0555-57Ab was detected when it passed in front of, or transited, its larger parent star, forming what is called an eclipsing stellar binary system. The parent star became dimmer in a periodic fashion, the signature of an orbiting object. Thanks to this special configuration, researchers can accurately measure the mass and size of any orbiting companions, in this case a small star. The mass of EBLM J0555-57Ab was established via the Doppler, wobble method, using data from the CORALIE spectrograph.

“This star is smaller, and likely colder than many of the gas giant exoplanets that have so far been identified,” said von Boetticher. “While a fascinating feature of stellar physics, it is often harder to measure the size of such dim low-mass stars than for many of the larger planets. Thankfully, we can find these small stars with planet-hunting equipment, when they orbit a larger host star in a binary system. It might sound incredible, but finding a star can at times be harder than finding a planet.”

This newly-measured star has a mass comparable to the current estimate for TRAPPIST-1, but has a radius that is nearly 30% smaller. “The smallest stars provide optimal conditions for the discovery of Earth-like planets, and for the remote exploration of their atmospheres,” said co-author Amaury Triaud, senior researcher at Cambridge’s Institute of Astronomy. “However, before we can study planets, we absolutely need to understand their star; this is fundamental.”

Although they are the most numerous stars in the Universe, stars with sizes and masses less than 20% that of the Sun are poorly understood, since they are difficult to detect due to their small size and low brightness. The EBLM project, which identified the star in this study, aims to plug that lapse in knowledge. “Thanks to the EBLM project, we will achieve a far greater understanding of the planets orbiting the most common stars that exist, planets like those orbiting TRAPPIST-1,” said co-author Professor Didier Queloz of Cambridge’ Cavendish Laboratory.

Reference
Alexander von Boetticher et al. ‘A Saturn-size low-mass star at the hydrogen-burning limit.’ Astronomy & Astrophysics (2017). arXiv:1706.08781

The researchers used data on hand grip strength from more than 140,000 participants in the UK Biobank study, combined with 50,000 additional individuals from the UK, Netherlands, Denmark and Australia, to identify sixteen common genetic variants that are associated with muscle strength.

Dan Wright, joint first author on this paper and a PhD student at the Medical Research Council Epidemiology (MRC) Unit at the University of Cambridge, said: “The very large number of individuals participating in UK Biobank provides a powerful resource for identifying genes involved in complex traits such as muscle strength, and helps us understand their underlying biology and its relevance to health.”

Many of these variants were located within or near to genes known to play a role in biological processes highly relevant to muscle function, including the structure and function of muscle fibres, and the communication of the nervous system with muscle cells.

Mutations in some of the genes highlighted are also known to be associated with severe monogenic syndromes – conditions caused by a single genetic mutations – characterised by compromised muscle function. This demonstrates that genetic variation in genes which cause serious muscular conditions may also influence differences in strength in the general population.

Dr Robert Scott, who co-led the study with colleagues from the MRC Epidemiology Unit, said: “While we have long suspected a role for genetics in the variation in muscle strength, these findings give the first insights into some of the specific genetic variants that underpin variation in strength.

“These could be important steps towards identifying new treatments to prevent or treat muscle weakness.”

Hand grip strength has been reported to be associated with many health outcomes, including risk of mortality, cardiovascular disease, and fracture – although it has been unclear whether variation in strength actually causes these outcomes, or simply reflects underlying disease processes.

Using the sixteen genetic variants identified for strength, the researchers were able to investigate the hypothesised causal link between strength and these adverse health outcomes. Their study found no evidence that lower strength causally increases risk of death or cardiovascular disease, but they did find evidence that higher muscular strength reduces risk of fracture, supporting the use of strength training interventions as a strategy to reduce risk of fractures. 

Professor Nick Wareham, director of the MRC Epidemiology Unit and a senior author of the study, noted: “This work highlights the importance of muscle strength in the prevention of fractures and the complications which can often follow a fall.”

Reference
Willems, SM et al. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nature Communications; 12 July 2017; DOI: 10.1038/ncomms16015

The announcement was made at a prize ceremony held at the Old Schools on 13 July. At the same event, one of Cambridge’s leading experts on EU law – and in particular, Brexit – received one of the Vice Chancellor’s Public Engagement with Research Awards for her work around the EU Referendum.

Professor Sir Leszek Borysiewicz, Vice-Chancellor of the University of Cambridge, says: “I would like to offer my warm congratulations to the recipients of our Impact and Public Engagement Awards. These are outstanding examples that reflect the tremendous efforts by our researchers to make a major contribution to society.”

Vice-Chancellor’s Impact Awards

The Vice-Chancellor’s Impact Awards were established to recognise and reward those whose research has led to excellent impact beyond academia, whether on the economy, society, culture, public policy or services, health, the environment or quality of life. Each winner receives a prize of £1,000 and a trophy, with the overall winner - Dr Alexander Patto from the Department of Physics – receiving £2,000.

This year’s winners are:

Overall winner: Dr Alexander Patto (Department of Physics)

WaterScope

Using an open-source flexure microscope, spin-out company WaterScope is developing rapid, automated water testing kits and affordable diagnostics to empower developing communities. Its microscopes are being used for education, to inspire future scientists from India to Colombia. Its open-source microscope is supporting local initiatives, with companies such as STIClab in Tanzania making medical microscopes from recycled plastic bottles.

Elroy Dimson (Judge Business School)

‘Active Ownership’: Engaging with investee companies on environmental and social issues

‘Active Ownership’ refers to commitment by asset owners and their portfolio managers to engage with the businesses they own, focusing on issues that matter to all stakeholders and to the economy as a whole, including environmental, social and governance (ESG) concerns. By providing evidence to guide ESG strategy, Professor Dimson’s research has had a substantial impact on investment policy and practice.

Professor Nick Morrell (Department of Medicine)

From genetics to new treatments in pulmonary arterial hypertension

Severe high blood pressure in the lungs, known as idiopathic pulmonary arterial hypertension, is a rare disease that affects approximately 1,000 people in the UK. The condition usually affects young women and average life expectancy is three to five years. Existing treatments improve symptoms but have little impact on survival. Professor Morrell has introduced routine genetic testing for this condition, and found that one in four patients carry a particular genetic mutation associated with more severe disease and worse survival. His research has identified new ways to treat the disease, the most promising of which is being commercialised through a university spin-out biotech company.

Professor Lawrence Sherman, Peter Neyroud, Dr Barak Ariel, Dr Cristobal Weinborn and Eleanor Neyroud (Institute of Criminology)

Cambridge Crime Harm Index

The Cambridge Crime Harm Index is a tool for creating a single metric for the seriousness of crime associated with any one offender, victim, address, community, or prevention strategy, supplementing traditional measures giving all crimes equal weight. The UK Office of National Statistics credits the index as the stimulus to institute its own, modified version from 2017. Police use the Cambridge index to target highest-harm offenders, victims, places, times and days, differences in crime harm per capita differs across communities or within them over time, adding precision to decisions for allocating scarce resources in times of budget cuts.

Vice-Chancellor’s Public Engagement with Research Awards

The Vice-Chancellor’s Public Engagement with Research Awards were set up to recognise and reward those who undertake quality engagement with research. Each winner receives a £1000 personal cash prize and a trophy. This year’s winners are:

Professor Catherine Barnard (Faculty of Law)

In the run up to the EU membership referendum Professor Barnard developed a range of outputs to explain key issues at stake including migration, which forms the basis of her research, in addition to the wider EU law remit. Harnessing the timeliness of the political climate, Barnard’s videos, online articles, radio and TV interviews have supported her engagement across 12 town hall events from Exeter to Newcastle, an open prison and round-table discussions with various public groups. She has also provided a number of briefing sessions to major political party MPs and peers. She has become a trusted public figure, and researcher, on EU law, Brexit and surrounding issues, ensuring that the voices of those key to the research process are heard and listened to.

Dr Elisa Laurenti (Wellcome/MRC Stem Cell Institute and Department of Haemotology)

Dr Laurenti has engaged over 2,500 people, at six separate events, with her Stem Cell Robots activity. She collaborated with a researcher in educational robotics to produce this robot-based activity, which maps a stem cell’s differentiation to become a specific cell type. The activity has provided a platform for children, families and adults to discuss ethics and clinical applications of stem cell research.

Dr Nai-Chieh Liu (Department of Veterinary Medicine)

Dr Liu has developed a non-invasive respiratory function test for short-skulled dog breeds, including French bulldogs and pugs, which suffer from airway obstruction. She has engaged with dog owners by attending dog shows, dog club meetings and breeders’ premises to break down barriers between publics and veterinarians working to improve the health of these dogs. As a result of this engagement, the UK French bulldog club and the Bulldog Breed Council have adopted health testing schemes based on Dr Liu’s research.

Dr Neil Stott and Belinda Bell (Cambridge Centre for Social Innovation, Judge Business School)

Dr Stott and Miss Bell established Cambridge Social Ventures to embed research around social innovation into a practical workshop to support emerging social entrepreneurs. Since the first workshop in 2014, they have reached almost 500 people wanting to create social change by starting and growing a business. The team goes to considerable efforts to reach out to participants from non-traditional backgrounds and to ensure workshops are inclusive and accessible to a wide range of people by incorporating online engagement with work in the community.

Amalia Thomas (Department of Applied Mathematics and Theoretical Physics)

Amalia Thomas researches photoelasticity, a property by which certain materials transmit light differently when subjected to a force. Amalia has developed an engaging exhibition for secondary school students comprising interactive elements, which uses photoelasticity to visualise force, work and power.

Dr Frank Waldron-Lynch, Jane Kennet and Katerina Anselmiova (Department of Medicine and Department of Clinical Biochemistry)

Since the commencement of their research programme to develop drugs for Type 1 Diabetes, Dr Waldron-Lynch, Ms Kennet and Ms Anselmiova have developed a public engagement programme to engage participants, patients, families, funders, colleagues, institutions, companies and the community, with the aim of ensuring that their research remains relevant to stakeholder needs. Amongst their outputs, the team has formed a patient support group in addition to developing an online engagement strategy through social media platforms. Most recently, they have collaborated with GlaxoSmithKline to offer patients the opportunity to participate in clinical studies at all stages of their disease.

Dr James Thaventhiran points to a diagram of a 14-year-old boy’s family tree. Some of the symbols are shaded black.

“These family members have a very severe form of immunodeficiency. The children get infections and chest problems, the adults have bowel problems, and the father died from cancer during the study. The boy himself had a donor bone marrow transplant when he was a teenager, but he remains very unwell, with limited treatment options.”

To understand the cause of the immunodeficiency, Thaventhiran, a clinical immunologist in Cambridge’s Department of Medicine, has been working with colleagues at the Great Northern Children’s Hospital in Newcastle, where the family is being treated.

Theirs is a rare disease, which means the condition affects fewer than 1 in 2,000 people. Most rare diseases are caused by a defect in the genetic blueprint that carries the instruction manual for life. Sometimes the mistake can be as small as a single letter in the three billion letters that make up the genome, yet it can have devastating consequences.

When Thaventhiran and colleagues carried out whole genome sequencing on the boy’s DNA, they discovered a defect that could explain the immunodeficiency. “We believe that just one wrong letter causes a malfunction in an immune cell called a dendritic cell, which is needed to detect infections and cancerous cells.”

Now, hope for an eventual cure for family members affected by the faulty gene is taking shape in the form of  ‘molecular scissors’ called CRISPR-Cas9. Discovered in bacteria, the CRISPR-Cas9 system is part of the armoury that bacteria use to protect themselves from the harmful effects of viruses. Today it is being co-opted by scientists worldwide as a way of removing and replacing gene defects.

One part of the CRISPR-Cas9 system acts like a GPS locator that can be programmed to go to an exact place in the genome. The other part – the ‘molecular scissors’ – cuts both strands of the faulty DNA and replaces it with DNA that doesn’t have the defect.

“It’s like rewriting DNA with precision,” explains Dr Alasdair Russell. “Unlike other forms of gene therapy, in which cells are given a new working gene but without being able to direct where it ends up in the genome, this technology changes just the faulty gene. It’s precise and it’s ‘scarless’ in that no evidence of the therapy is left within the repaired genome.”

Russell heads up a specialised team in the Cancer Research UK Cambridge Institute to provide a centralised hub for state-of-the-art genome-editing technologies.

“By concentrating skills in one area, it means scientists in different labs don’t reinvent the wheel each time and can keep pace with the field,” he explains. “At full capacity, we aim to be capable of running up to 30 gene-editing projects in parallel.

“What I find amazing about the technology is that it’s tearing down traditional barriers between different disciplines, allowing us to collaborate with clinicians, synthetic biologists, physicists, engineers, computational analysts and industry, on a global scale. The technology gives you the opportunity to innovate, rather than imitate. I tell my wife I sometimes feel like Q in James Bond and she laughs.”

Russell’s team is using the technology both to understand disease and to treat it. Together with Cambridge spin-out DefiniGEN, they are rewriting the DNA of a very special type of cell called an induced pluripotent stem cell (iPSC). These are cells that are taken from the skin of a patient and ‘reprogrammed’ to act like one of the body’s stem cells, which have the capacity to develop into almost any other cell of the body.

In this case, they are turning the boy’s skin cells into iPSCs, using CRISPR-Cas9 to correct the defect, and then allowing these corrected cells to develop into the cell type that is affected by the disease – the dendritic cell. “It’s a patient-specific model of the cure in a Petri dish,” says Russell.

The boy’s family members are among a handful of patients worldwide who are reported to have the same condition and among around 3,500 in the UK who have similar types of immunodeficiency caused by other gene defects. With such a rare group of diseases, explains Thaventhiran, it’s important to locate other patients to increase the chance of understanding what happens and how to treat it.

He and Professor Ken Smith in the Department of Medicine lead a programme to find, sequence, research and provide diagnostic services to these patients. So far, 2,000 patients (around 60% of the total affected in the UK) have been recruited, making it the largest worldwide cohort of patients with primary immunodeficiency.

“We’ve now made 12 iPSC lines from different patients with immunodeficiency,” adds Thaventhiran, who has started a programme for gene editing all of the lines. “This means that for the first time we’ll be able to investigate whether correcting the mutation corrects the defect – it’ll open up new avenues of research into the mechanisms underlying these diseases.”

But it’s the possibility of using the gene-edited cells to cure patients that excites Thaventhiran and Russell. They explain that one option might be to give a patient repeated treatments of their own gene-edited iPSCs. Another would be to take the patient’s blood stem cells, edit them and then return them to the patient.

The researchers are quick to point out that although the technologies are converging on this possibility of truly personalised medicine, there are still many issues to consider in the fields of ethics, regulation and law.

Dr Kathy Liddell, who leads the Cambridge Centre for Law, Medicine and Life Sciences, agrees: “It’s easy to see the appeal of using gene editing to help patients with serious illnesses. However, new techniques could be used for many purposes, some of which are contentious. For example, the same technique that edits a disease in a child could be applied to an embryo to stop a disease being inherited, or to ‘design’ babies. This raises concerns about eugenics.

“The challenge is to find systems of governance that facilitate important purposes, while limiting, and preferably preventing, unethical purposes. It’s actually very difficult. Rules not only have to be designed, but implemented and enforced. Meanwhile, powerful social drivers push hard against ethical boundaries, and scientific information and ideas travel easily – often too easily – across national borders to unregulated states.”

A further challenge is the business case for carrying out these types of treatments, which are potentially curative but are costly and benefit few patients. One reason why rare diseases are also known as orphan diseases is because in the past they have rarely been adopted by drug companies.

Liddell adds: “CRISPR-Cas9 patent wars are just warming up, demonstrating some of the economic issues at stake. Two US institutions are vigorously prosecuting their own patents, and trying to overturn the others. There will also be cross-licensing battles to follow.”

“The obvious place to start is by correcting diseases caused by just one gene; however, the technology allows us to scale up to several genes, making it something that could benefit many, many different diseases,” adds Russell. “At the moment, the field as a whole is focused on ensuring the technology is safe before it moves into the clinic. But the advantage of it being cheap, precise and scalable should make CRISPR attractive to industry.”  

In ten years or so, speculates Russell, we might see bedside ‘CRISPR on a chip’ devices that screen for mutations and ‘edit on the fly’. “I’m really excited by the frontierness of it all,” says Russell. “We feel that we’re right on the precipice of a new personalised medical future.”

The signing will mark the grant of 15 million złotys (approximately £3.1 million),  allocated to the University of Warsaw by the Polish Ministry of Science and Higher Education, to endow in perpetuity a Polish Studies Programme at Cambridge.

The programme will provide opportunities for research collaboration, as well as teaching in Polish language, literature and culture.

The programme’s research output will be complemented by a series of high-profile public events that will aim to stimulate research in Polish culture and society, and promote greater understanding of Poland’s role in European history as well as its position as a rising economic power.
The new initiative will build on the success of the existing four-year pilot programme in Polish Studies at the University, led by Dr Stanley Bill of Cambridge’s Department of Slavonic Studies and supported by the Foundation for Polish Science (FNP), the M.B. Grabowski Fund, the Zdanowich Fund and Cambridge’s School of Arts and Humanities.

Professor Sir Leszek Borysiewicz, Vice-Chancellor of the University of Cambridge, signed the agreement with the Rector of the University of Warsaw, Professor Marcin Pałys.

Professor Martin Millett, Head of the School of Arts and Humanities at the University of Cambridge, said: “We are delighted to be strengthening this relationship with our colleagues in Poland, which is not only of strategic importance to the University of Cambridge, but of significant import at this time in the history of Europe.”

“The continuity of Polish Studies at the University of Cambridge is an opportunity for both parties to develop teaching and research cooperation,” said Assistant Professor Maciej Duszczyk, Vice Rector for Research at the University of Warsaw. He added: “An Advisory Board for the new Polish Studies programme at Cambridge –consisting of representatives from the University of Cambridge, the University of Warsaw, and the Foundation for Polish Science—will be tasked with setting the framework for our collaboration.”

The agreement was concluded with the support of Poland’s Ministry of Science and Higher Education. 

In the autumn, representatives of both universities will meet in Warsaw to take part in an event to marking the enhanced collaboration.

Individuals who have had a stroke are at risk of a second stroke, which carries a greater risk of disability and death than first time strokes. In fact, one third of all strokes occur in individuals who have previously had a stroke. To prevent this recurrence, patients are offered secondary preventative medications; however, adherence is a problem with 30% of stroke patients failing to take their medications as prescribed.

To examine the barriers to taking these medications, researchers at the University of Cambridge and Queen Mary University, London (QMUL), analysed posts to TalkStroke, a UK-based online forum hosted by the Stroke Association, across a seven year period (2004-2011).  The forum was used by stroke survivors and their carers.

The team, led by Dr Anna De Simoni, a lecturer in Primary Care Research at QMUL and visiting researcher at the Department of Public Health and Primary Care, University of Cambridge, has previously used the forum to explore issues such as the impairment that can make it difficult for stroke survivors to maintain a job.

The findings of the study, which looked at posts by 84 participants, including 49 stroke survivors and 33 caregivers, are published today in the journal BMJ Open. The Stroke Association gave the researchers permission to analyse the results, and to prevent identification of individuals, the team did not use verbatim comments.

Among the reasons cited by the forum users, side effects were a major factor in decisions to stop taking medication. Several contributors had experienced negative side effects and as a result had stopped taking the medication, sometimes in consultation with their GP and other times unilaterally. Others reported that they, or the person they were caring for, had stopped taking the medication after reading negative stories in the press about side effects.

Other users expressed concerns over the medication they were offered. There were conflicting views about the efficacy of the medications – some contributors believed they were very important, while others believed that their risk could be managed by lifestyle changes alone.

Contributors also reported mixed views of healthcare professionals – some felt confident in their doctor’s decision, while others questioned their decisions, some even questioning their motivation for prescribing particular drugs.

“These findings have highlighted the need for an open, honest dialogue between patients and/or their carers, and healthcare professionals,” says Dr De Simoni. “Doctors need to listen to these concerns, discuss the benefits and drawbacks of taking the medication, and be willing to support a patient’s informed decision to refuse medications.”

However, perceptions did not present the only barriers to adherence: there were often practical considerations. Drugs were sometimes too large and difficult to swallow, or a drug regime was too burdensome. The complexities of the drug regimens sometimes meant having to develop routines and strategies to ensure patients kept to them. One survivor described having to pay for the medications by credit card as she was unable to work and had no money or benefits coming in.

“By analysing people’s views as expressed in online forums, where they are more open and less guarded, we’ve seen some valuable insights into why some stroke survivors have difficulty adhering to their medication,” says PhD candidate and first author James Jamison from the Department of Public Health and Primary Care at Cambridge.

“Challenging negative beliefs about medication and adopting practices that make routines for taking medication simpler, particularly for those patients who have suffered disability as a result of stroke, should increase adherence and ultimately improve health outcomes.”

The research was supported by the National Institute of Health Research, the Stroke Association and the British Heart Foundation.

For more information about statins, visit NHS Choices. 

Reference
Jamison, J et al. Barriers and facilitators to adherence to secondary stroke prevention medications after stroke: Analysis of survivors’ and caregivers’ views from an online stroke forum. BMJ Open; 19 July 2017; DOI: 10.17863/CAM.10458

When Jane Austen died on 18 July 1817 she had been working on a new novel. With four published novels (all published anonymously), she had accrued an enthusiastic following. The title she chose for this latest book was The Brothers. After her death, it was released as Sanditon, the name of the seaside town that features in the story.

The three notebooks in which Austen wrote Sanditon are among the greatest treasures held by King’s College Archive. The College will tomorrow display two of these notebooks in an exhibition in its Old Library. The remaining notebook is on loan to the Bodleian Library in Oxford.

Sanditon is the star attraction of a Jane Austen Open Day organised to display around 40 items. The objects, arranged in three cases, comprise books and letters – and together represent King’s College’s biggest-ever display of Austen-related material.

The autograph manuscript of Sanditon can only be described as priceless. The manuscript is rarely displayed as both the ink and paper used are vulnerable to light. It was last shown to the public for one day in 2013.

“A .digital version of Sanditon is available but we want people to have the chance to see the manuscript itself,” said Dr James Clements, King’s College Librarian.

“We know that Jane began writing Sanditon in January 1817 and that her last entry is dated 18th March 1817, by which time she’d completed 12 chapters. The novel begins with a carriage accident and charts familiar Austen territory with its wry and witty exploration of society politics.”

The Sanditon manuscript was given to King’s College in 1930 by Austen’s great-great niece, Mary Isabella Lefroy, whose brother-in-law (Augustus Austen-Leigh) had been Provost of the College. The letter in which she talks about giving the notebooks to the College is on display. In it, she presents Sanditon in memory of “the most popular Provost, and Provostess ‘Kings’ has ever had”.

Also on display are first editions of the Austen novels published in her lifetime: Sense and Sensibility, Pride and Prejudice, Mansfield Park, and Emma, all published anonymously. Only after Austen’s death, when her novels Northanger Abbey and Persuasion were first published in December 1817 (also in the exhibition), was she identified as the author.

The Georgian town of Bath figures in several Austen novels. A copy of The New Bath Guide for 1807, on display alongside the first edition of Persuasion, sets the scene with stunning engravings of life at the fashionable spa.

Other items of interest in the exhibition include a letter from Austen to her publisher, in which she takes a reviewer to task, and examples of early editions of Austen’s novels, including the first edition of Emma to appear in the USA, and a Railway Library edition of Pride and Prejudice“in fancy boards” priced one shilling.

The Jane Austen Open Day at King’s College takes place tomorrow (18 July 2017) from 10am to 4pm. For details and directions, go to https://kcctreasures.com/  There will be another chance to see the display as part Open Cambridge on 8 and 9 September 2017.

The exhibition has been made possible through a cataloguing and outreach project supported by the Heritage Lottery Fund.