Heart disease is the greatest killer in the world today, and it is widely accepted that our genes interact with traditional lifestyle risk factors, such as smoking, obesity and/or a sedentary life to promote an increased risk of cardiovascular disease.

In addition to the effects of adult lifestyle, there is already evidence that the gene-environment interaction before birth may be just as, if not more, important in ‘programming’ future heart health and heart disease. For example, human studies in siblings show that children born to a mother who was obese during pregnancy are at greater risk of heart disease than siblings born to the same mother after bariatric surgery to reduce maternal obesity. Such studies have provided strong evidence in humans that the environment experienced during critical periods of development can directly influence long-term cardiovascular health and heart disease risk.

The new research, funded by the British Heart Foundation and the Biotechnology and Biological Sciences Research Council, shows that adult offspring from pregnancies complicated by chronic hypoxia – lower-than-normal oxygen levels – have increased indicators of cardiovascular disease such as high blood pressure and stiffer blood vessels. Chronic hypoxia in the developing baby within the womb is one of the most common outcomes of complicated pregnancy in humans. It occurs as a result of problems within the placenta, as can occur in preeclampsia, gestational diabetes or maternal smoking.

The study, led by Professor Dino Giussani from the Department of Physiology, Development and Neuroscience and published today in the journal PLOS Biology, used pregnant sheep to show that maternal treatment with the antioxidant vitamin C during a complicated pregnancy could protect the adult offspring from developing hypertension and heart disease. The work therefore not only provides evidence that a prenatal influence on later heart disease in the offspring is indeed possible but also shows the potential to protect against it by “bringing preventative medicine back into the womb,” as Dr Kirsty Brain, first author of the study, puts it.

It turns out that vitamin C is a comparatively weak antioxidant, and while the Cambridge study provides a proof-of-principle, future work will focus on identifying alternative antioxidant therapies that could prove more effective in human clinical practice.

“Our discoveries emphasise that when considering strategies to reduce the overall burden of heart disease, much greater attention to prevention rather than treatment is required,” adds Professor Giussani. “Treatment should start as early as possible during development, rather than waiting until adulthood when the disease process has become irreversible.”

Professor Giussani stresses that it is too soon to consider vitamin C as a potential supplement for mothers. Any mothers concerned about their baby’s development in the womb should speak to their doctor before changing their diet or using supplements.

The work draws attention to a new way of thinking about heart disease with a much longer-term perspective, focusing on prevention rather than treatment.

Reference
Brain KL, Allison BJ, Niu Y, Cross CM, Itani N, Kane AD, et al. Intervention against hypertension in the next generation programmed by developmental hypoxia. PLoS Biol 17(1): e2006552. https://doi.org/10.1371/journal.pbio.2006552

Professor Julian Dowdeswell, Director of the Scott Polar Research Institute, is chief scientist on the ambitious expedition, which will use drones, satellites and autonomous underwater vehicles to study ice conditions in the Weddell Sea in unprecedented detail.

The Weddell Sea is also the site of one of the most famous stories from the ‘Heroic Age’ of polar exploration.

The Imperial Trans-Antarctic Expedition 1914-17 set out to cross Antarctica via the South Pole. However, in November 1915, Shackleton and his 28-man crew were confronted with one of the worst disasters in Antarctic history when Endurance was trapped, crushed and sunk by pack ice. The outside world was unaware of their predicament or location, food was scarce and the chance of survival was remote.

In this film, Professor Dowdeswell tells the incredible story of Endurance, and how he and the other members of the Weddell Sea expedition hope to locate the wreckage of one of the most iconic vessels in polar exploration.

More than six in ten adults in the UK are overweight, and one in four adults is obese. By age five, almost one in four children is either overweight or obese. Excess weight increases the risk of related health problems including type 2 diabetes and heart disease.

While it is well known that changes in our environment, such as easy access to high calorie foods and sedentary lifestyles, have driven the rise in obesity in recent years, there is considerable individual variation in weight within a population that shares the same environment. Some people seem able to eat what they like and remain thin. This has led some people to characterise overweight people as lazy or lacking willpower.

With support from Wellcome and the European Research Council, a team led by Professor Sadaf Farooqi at the Wellcome-MRC Institute of Metabolic Science, University of Cambridge, established the Study Into Lean and Thin Subjects – STILTS – to examine why and how some people find it easier to stay thin than others. Studies of twins have shown that variation in body weight is largely influenced by our genes. To date studies have overwhelmingly focused on people who are overweight. Hundreds of genes have been found that increase the chance of a person being overweight and in some people faulty genes can cause severe obesity from a young age.

Professor Sadaf Farooqi’s team were able to recruit 2,000 people who were thin (defined as a body mass index (BMI) of less than 18 kg/m2) but healthy, with no medical conditions or eating disorders. They worked with general practices across the UK, taking saliva samples to enable DNA analysis and asking participants to answer questions about their general health and lifestyles. It is thought to be the only cohort of its kind in the world and the researchers say that the UK’s National Institute for Health Research – the National Health Service’s research infrastructure – strongly enabled and supported their research.

In a study published today in the journal PLOS Genetics, Professor Farooqi’s team collaborated with Dr Inês Barroso’s team at the Wellcome Sanger Institute to compare the DNA of some 14,000 people –1,622 thin volunteers from the STILTS cohort, 1,985 severely obese people and a further 10,433 normal weight controls.

Our DNA comprises of a sequence of molecules known as base pairs, represented by the letters A, C, G and T. Strings of these base pairs form genetic regions (which include or make up our genes). Our genes provide the code for how our body functions and changes in the spelling – for example, a C in place of an A – can have subtle or sometimes dramatic changes on features such as hair colour and eye colour but also on a person’s weight.

The team found several common genetic variants already identified as playing a role in obesity. In addition, they found new genetic regions involved in severe obesity and some involved in healthy thinness.

To see what impact these genes had on an individual’s weight, the researchers added up the contribution of the different genetic variants to calculate a genetic risk score.

“As anticipated, we found that obese people had a higher genetic risk score than normal weight people, which contributes to their risk of being overweight. The genetic dice are loaded against them,” explains Dr Barroso.

Importantly, the team also showed that thin people, had a much lower genetic risk score – they had fewer genetic variants that we know increase a person’s chances of being overweight.

“This research shows for the first time that healthy thin people are generally thin because they have a lower burden of genes that increase a person’s chances of being overweight and not because they are morally superior, as some people like to suggest,” says Professor Farooqi. “It’s easy to rush to judgement and criticise people for their weight, but the science shows that things are far more complex. We have far less control over our weight than we might wish to think.”

Three out of four people (74%) in the STILTS cohort had a family history of being thin and healthy and the team found some genetic changes that were significantly more common in thin people, which they say may allow them to pinpoint new genes and biological mechanisms that help people stay thin.

“We already know that people can be thin for different reasons” says Professor Farooqi. “Some people are just not that interested in food whereas others can eat what they like, but never put on weight. If we can find the genes that prevent them from putting on weight, we may be able to target those genes to find new weight loss strategies and help people who do not have this advantage.”

The research was funded by the European Research Council and Wellcome.

Reference
Riveros-McKay, F, Mistry, V et al. Genetic architecture of human thinness compared to severe obesity. PLOS Genetics; 24 Jan 2019; DOI:

They have a developed a way of calculating the risk of developing the disease by combining information on family history and genetics with other factors such as weight, age at menopause, alcohol consumption and use of hormone replacement therapy.

Although individually some of these things have a small impact on the likelihood of developing the disease, researchers found that by considering all of them at once, plus family history and genetics, they can identify groups of women who have different risks of developing breast cancer.

Importantly, for the first time, researchers have taken into account more than 300 genetic indicators for breast cancer. This makes calculating the risk much more precise than ever before.

From this, the researchers have created an online calculator for GPs to use in their surgeries.

Some GPs, practice nurses and genetic counsellors are testing this tool before it is considered for wider use. Doctors are prompted to answer a series of online questions about their patient including their medical and family history, whether they have any known genetic alterations linked to cancer, their weight and whether they drink alcohol.

In the future, information like this could help to tailor breast cancer screening depending on an individual’s risk. For example, it could help determine what age they are first invited for breast screening or how regularly they are invited to receive it.

The risk calculation could also help people to make decisions about preventative therapy – such as identifying women at high risk who may benefit from taking the drug tamoxifen – as well as encouraging women to think about the ways they could reduce the risk themselves, for example trying to keep a healthy weight.

Professor Antonis Antoniou, lead author at the Department of Public Health and Primary Care, University of Cambridge, said: “This is the first time that anyone has combined so many elements into one breast cancer prediction tool. It could be a game changer for breast cancer because now we can identify large numbers of women with different levels of risk – not just women who are at high risk.

“This should help doctors to tailor the care they provide depending on their patients’ level of risk. For example, some women may need additional appointments with their doctor to discuss screening or prevention options and others may just need advice on their lifestyle and diet.

“We hope this means more people can be diagnosed early and survive their disease for longer, but more research and trials are needed before we will fully understand how this could be used.”

Breast cancer is the most common cancer in the UK. Nearly 55,000 women are diagnosed with the disease each year. But a large proportion of breast cancer cases occur in people who are at an increased risk. Cancer Research UK has helped to double breast cancer survival over the last 40 years.

Dr Richard Roope, Cancer Research UK’s GP expert, said: “Research like this is hugely exciting because in the future it will enable us to offer much more tailored care which will benefit patients and make best use of the services that we have available.

“Although having an increased risk of breast cancer means a woman is more likely to develop the disease – it’s by no means a certainty. A woman at high risk may never get breast cancer just as a woman at low risk still could. But any woman with concerns should speak to her GP to discuss the options.”

Reference
Lee, A et al. BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors.Genetics in Medicine; 15 Jan 2019; DOI: 10.1038/s41436-018-0406-9

Adapted from a press release by Cancer Research UK

Breathe London will use a range of cutting-edge fixed and mobile sensors to build up a real-time, hyperlocal image of London’s air quality.  The data these monitors collect from across the capital will provide an unprecedented level of detail about London’s air quality crisis and deliver new insight into the sources of pollution.

Professor Rod Jones from Cambridge’s Department of Chemistry and his group are leaders in the development and use of low-cost air quality sensors, which have been used in projects around the world from Heathrow Airport to Beijing and Dhakar.  They are supporting the Breathe London project by providing their expertise in sensors and through the analysis and interpretation of results from the sensor networks and two Google Street View cars which have been equipped with air pollution monitoring equipment.

The data generated by this new network will be available for the public to view on an interactive map on the Breathe London website. The map will show Londoners the condition of the air they are currently breathing and allow more accurate pollution forecasting.

The Breathe London project was devised by City Hall and the C40 Cities Climate Leadership Group, a global alliance of 90 cities committed to addressing climate change. The project has brought together some of the UK’s top health and scientific experts with leading technology companies and the Environmental Defense Fund.

Baroness Bryony Worthington, Executive Director of the Environmental Defense Fund, said: “The Breathe London partnership is breaking new ground. We’re developing new scientific approaches using the latest technologies to explore London’s air quality in unprecedented detail.

“This will provide information for both the public and decision makers that can help drive better solutions to a problem that affects every Londoner. The support of Mayor Khan, C40 Cities, CIFF and all the partners has been invaluable and together we hope to advance air quality management in London, the UK and cities worldwide.”

“By combining fixed and mobile monitors, and by sampling air quality at so many locations, this project paints a far more accurate picture of air pollution across London,” said Jones. “Air pollution is a complex challenge, affected by many different factors, so getting the best possible data is vital. I’m especially looking forward to the possibility of replicating this project in other cities around the world.”

The project is funded by the Clean Air Fund at the Children’s Investment Fund Foundation (CIFF) and managed by C40 Cities.

The alternative explanation to the so-called ‘Planet Nine’ hypothesis, put forward by researchers at the University of Cambridge and the American University of Beirut, proposes a disc made up of small icy bodies with a combined mass as much as ten times that of Earth. When combined with a simplified model of the solar system, the gravitational forces of the hypothesised disc can account for the unusual orbital architecture exhibited by some objects at the outer reaches of the solar system.

While the new theory is not the first to propose that the gravitational forces of a massive disc made of small objects could avoid the need for a ninth planet, it is the first such theory which is able to explain the significant features of the observed orbits while accounting for the mass and gravity of the other eight planets in our solar system. The results are reported in the Astronomical Journal.

Beyond the orbit of Neptune lies the Kuiper Belt, which is made up of small bodies left over from the formation of the solar system. Neptune and the other giant planets gravitationally influence the objects in the Kuiper Belt and beyond, collectively known as trans-Neptunian Objects (TNOs), which encircle the Sun on nearly-circular paths from almost all directions.

However, astronomers have discovered some mysterious outliers. Since 2003, around 30 TNOs on highly elliptical orbits have been spotted: they stand out from the rest of the TNOs by sharing, on average, the same spatial orientation. This type of clustering cannot be explained by our existing eight-planet solar system architecture and has led to some astronomers hypothesising that the unusual orbits could be influenced by the existence of an as-yet-unknown ninth planet.

The ‘Planet Nine’ hypothesis suggests that to account for the unusual orbits of these TNOs, there would have to be another planet, believed to be about ten times more massive than Earth, lurking in the distant reaches of the solar system and ‘shepherding’ the TNOs in the same direction through the combined effect of its gravity and that of the rest of the solar system.

“The Planet Nine hypothesis is a fascinating one, but if the hypothesised ninth planet exists, it has so far avoided detection,” said co-author Antranik Sefilian, a PhD student in Cambridge’s Department of Applied Mathematics and Theoretical Physics. “We wanted to see whether there could be another, less dramatic and perhaps more natural, cause for the unusual orbits we see in some TNOs. We thought, rather than allowing for a ninth planet, and then worry about its formation and unusual orbit, why not simply account for the gravity of small objects constituting a disc beyond the orbit of Neptune and see what it does for us?”

Professor Jihad Touma, from the American University of Beirut, and his former student Sefilian modelled the full spatial dynamics of TNOs with the combined action of the giant outer planets and a massive, extended disc beyond Neptune. The duo’s calculations, which grew out of a seminar at the American University of Beirut, revealed that such a model can explain the perplexing spatially clustered orbits of some TNOs. In the process, they were able to identify ranges in the disc’s mass, its ‘roundness’ (or eccentricity), and forced gradual shifts in its orientations (or precession rate), which faithfully reproduced the outlier TNO orbits.

“If you remove planet nine from the model and instead allow for lots of small objects scattered across a wide area, collective attractions between those objects could just as easily account for the eccentric orbits we see in some TNOs,” said Sefilian, who is a Gates Cambridge Scholar and a member of Darwin College.

Earlier attempts to estimate the total mass of objects beyond Neptune have only added up to around one-tenth the mass of the Earth. However, in order for the TNOs to have the observed orbits and for there to be no Planet Nine, the model put forward by Sefilian and Touma requires the combined mass of the Kuiper Belt to be between a few to ten times the mass of the Earth.

“When observing other systems, we often study the disc surrounding the host star to infer the properties of any planets in orbit around it,” said Sefilian. “The problem is when you’re observing the disc from inside the system, it’s almost impossible to see the whole thing at once. While we don’t have direct observational evidence for the disc, neither do we have it for Planet Nine, which is why we’re investigating other possibilities. Nevertheless, it is interesting to note that observations of Kuiper belt analogues around other stars, as well as planet formation models, reveal massive remnant populations of debris.

“It’s also possible that both things could be true – there could be a massive disc and a ninth planet. With the discovery of each new TNO, we gather more evidence that might help explain their behaviour.”

Reference:
Antranik A. Sefilian and Jihad R. Touma. ‘Shepherding in a self-gravitating disk of trans-Neptunian objects.’ Astronomical Journal (2019).

A team from the Behavioural and Clinical Neuroscience Institute at the University of Cambridge has developed and tested ‘Decoder’, a new game that is aimed at helping users improve their attention and concentration. The game is based on the team’s own research and has been evaluated scientifically.

Read more here.

The study, commissioned by the UK Foreign and Commonwealth Office (FCO) and produced by the REAL Centre at the Faculty of Education, University of Cambridge, reveals that the most disadvantaged girls rarely reach high levels of education, beyond primary, that benefit most from national and aid funding. In Nigeria and Pakistan, girls from poor rural households average just one year at school, while rich urban boys enjoy 11 or 12 years of study.

National governments and donor countries must show greater political commitment if global goals on gender equality in education are to be reached, according to the report, 12 Years of Quality Education for All Girls: A Commonwealth Perspective. The report will be launched at the Education World Forum, the world’s largest gathering of education and skills ministers, in London on Monday 21 January 2019.

Barriers to access

The study highlights an array of barriers that prevent girls accessing education, including gender-based violence within and on the way to school, and absenteeism during menstruation because of a lack of availability of sanitary protection. For marginalised girls, cost is also a key barrier in sending girls to school, with poverty leading some girls to have sex with men who provide them with the essentials of secondary schooling that their family cannot afford. Schools must be made “safe spaces” for girls, particularly in areas affected by conflict, say the authors, while cash support for the poorest families may help ease financial pressures and free up daughters to go to school.

Professor Pauline Rose, Director of the REAL Centre and author of the report, said: “Evidence shows us what works to address barriers that marginalised girls face in their access and learning. Much more needs to be done to implement these interventions at far greater scale. It is vital that current political uncertainties do not jeopardise the prioritisation of investment in girls’ education to enable this to happen.”

The report was commissioned by the Platform for Girls’ Education, co-chaired by the UK Foreign Secretary and Kenyan Cabinet Secretary for Education. The platform, a group of 12 influential figures across the Commonwealth, was created after the Commonwealth Heads of Government Meeting (CHOGM) in April 2018 affirmed the importance of 12 years of quality education for all, particularly marginalised girls. Achieving that target by 2030 is one of the UN Sustainable Development Goals signed up to in 2015 by leaders across the globe.

Equality a “distant reality”

The study finds that, over the past 20 years, considerable progress has been made in increasing access to primary schooling in the 53 countries of the Commonwealth. There are now equal proportions of boys and girls primary enrolled in 31 out of 44 Commonwealth countries with data. But despite this progress, “12 years of schooling remains a distant reality for many of the most disadvantaged girls residing in Commonwealth countries,” the report says. Gender parity in enrolment has sometimes been achieved even though primary schooling is still not universal: in 2017, 137 million primary-and-secondary school aged children were out of school in these countries, approximately half of them girls.

In 15 out of 21 Commonwealth countries with available data, poor rural girls spend no more than five years in school, and so have little chance of making the transition to secondary school. In six countries, they spend only one or two years in education. Children and adolescents affected by conflict are most likely to be out of school, and refugee girls are particularly at risk: they are half as likely as their male counterparts to be in secondary school.

Poor learning in school

Even those children in school are frequently not learning the basics, researchers found. The recently launched Human Capital Index shows that girls’ education fares far worse when years in school is adjusted for whether or not children are learning. In 14 out of the 26 countries with data, girls who are in school are learning only for the equivalent of six years or less. The picture is likely to be even starker for girls in rural areas and those facing other forms of disadvantage.

Disadvantage starts early, the study says, with many girls denied early years investment that is proven to boost educational achievement later. In eight of 14 Commonwealth countries with data, no more than 40 percent of poor rural girls have access to pre-primary education, and in three out of these eight countries, fewer than 10 percent are enrolled.

Governments should do more to target funding on lower levels of education and marginalised groups, the report argues. In 33 out of 45 Commonwealth countries with data, governments are spending far more on post-primary levels of education than on primary schooling, even though the probability of the most disadvantaged girls reaching these levels of education is extremely low. Of the 35 Commonwealth countries with data on pre-primary spending, 25 governments are spending less than five percent of their education budgets on pre-primary education.

Early years not prioritised

The same failure to prioritise the early years is seen in education aid spending. Funding for primary education fell from around two thirds in 2002 to under a half (47%) by 2016, and a mere 0.4 percent of education aid to Commonwealth countries was spent on pre-primary education. By contrast, 10 percent is spent on scholarships to allow students from aid-recipient Commonwealth countries to study in donor countries, even though only the most privileged benefit from such schemes.

In addition, only around five percent of total education aid appears to be spent with the main objective of achieving gender equality. The UK alone bucks the trend, with all but 2% of education aid targeting gender equality directly or significantly affecting it.

To tackle discrimination and work towards gender equality in education, governments of Commonwealth countries must show visible high-level political commitment backed by resources, the study concludes. Funding towards early childhood education and early learning should be prioritised.

Support for girls at puberty

There must also be steps to address the particular challenges marginalised girls face at puberty, such as provision of sanitary pads in schools, and moves to keep girls safe and secure in school, including providing female staff, secure buildings and door-to-door transport between school and home. More broadly, gender-sensitive teaching practices and materials are needed to ensure discriminatory stereotypes are not enforced, says the study.

The report sets out three priorities for further action, including “high-level, visible political leadership” towards gender equality in education, backed up by sufficient resources to reach the most marginalised girls. Investment in early years education is also vital, together with making girls’ education a priority in wider national development planning.

For more information, contact: Professor Pauline Rose or Faculty of Education Communications Manager Lucy Ward on lw28@cam.ac.uk

International finance markets lagged behind punters having a flutter when it came to getting the right result on EU referendum night, according to research.

A study shows that gamblers sensed the Leave vote coming an hour before the currency experts in the city – creating a window of “arbitrage” during which the price difference between betting and FX markets yielded up to a 7% return on the pound.

Researchers from the Faculty of Economics compared the behaviours of the Betfair betting market and the sterling-dollar exchange rate from closure of the polls at 10pm, when odds of 10 to 1 were being offered on Brexit.

Both markets were “informationally inefficient”: very slow to react despite the data already available, as well as that flooding in from vote counts across the country. This meant there was money to be made by trading early on either market, say researchers.

The study shows the betting market moved to a Leave result around 3am, by which time Brexit odds had reversed (1 to 10). Yet the foreign exchange market didn’t fully adjust to the reality of Brexit until around 4am. At 4:40am the BBC predicted a Leave victory.

The difference in efficiency between the two markets created an hour when selling sterling and hedging the result of the referendum on Betfair would have made up to nine US cents of profit per UK pound – a significant “unleveraged return” that, in theory at least, could have seen astute traders make millions.

Researchers say the findings support the idea that gambling, or so-called “prediction markets”, might provide better forecasts of election outcomes than either experts or polls.

“Clearly, punters trading on Betfair are a different group of people to those dealing in FX for international finance. It looks like the gamblers had a better sense that Leave could win, or that it could at least go either way,” said Dr Tom Auld, lead author of the study published recently in the International Journal of Forecasting.

“Our findings suggest that participants across both markets suffered a behavioural bias as the results unfolded. Initially, both traders and gamblers could not believe the UK was voting to leave the EU, but this disbelief lingered far longer in the city.”

Auld and his co-author Prof Oliver Linton used the expected outcomes for each voting area – data that was publicly available prior to the referendum – to create a “forecasting model”.

By adjusting it with each actual result in turn, they say that their model would have predicted the final result from around 1:30am had it been deployed on the night.

“According to theories such as the ‘efficient market hypothesis’, the markets discount all publicly available information, so you cannot get an edge on the market with data already out there,” said Auld.

“However, using data publicly available at the time we show that the financial markets were very inefficient, and should have predicted Brexit possibly over two hours before they actually did.”

“If there is a second referendum, the vote should be better understood by markets – in line with a theoretical concept called the adaptive markets hypothesis. Studies such as ours will mean that market participants will be primed to profit from any possible opportunities and inefficiencies,” he said.

The researchers compared their modelling with gambling and currency market data from EU referendum night. The website Betfair provided data from their exchange platform – the world’s largest betting exchange – between 10am on June 23 and 5am on June 24.

More than 182,000 individual bets were placed with Betfair and over 88,000 trades were made in the GBP futures market during this seven-hour window. Trading on Brexit broke records for a political event on Betfair, with over £128m wagered including over £50m that was matched on the night of the vote itself.

“Prediction markets such as betting exchanges are an ‘incentive compatible’ way to elicit the private opinions of participants, as people are putting their money where their mouth is, whereas what they tell pollsters can be cheap talk,” added Auld.

“Prediction markets could in theory be used to help value or price financial assets during events such as major votes. This is an area I will be focusing on for future research.”

During a pilot study, published today in the journal BMJ Open, seventeen patients received daily automated telephone calls for one month. All patients had high blood pressure and were recruited from GP practices in East of England. The calls were tailored to patients’ needs and provide them with advice and support about taking their prescribed medicines. The calls also asked a series of interactive questions and reacted to the patients’ answers.

Examples of the messages included:

Please do not forget to take your tablets. To achieve better control over high blood pressure, you will need to take them every day.

This is your message for your blood pressure tablets. One easy way to remember your tablets, is to take them with another daily activity, such as your morning cup of tea. If they are always done together, it will be harder to forget.

Please keep taking your tablets as prescribed even if you are well and feeling healthy. High blood pressure is one of those things that unless you actually feel it you’re not aware that it is a problem.

Taking your medications as prescribed will support you to keep enjoying things or activities that are important to you.

Whatever the day may holds, please do not forget to take your tablets. To achieve better control over high blood pressure, you will need to take them every day.

The patients completed questionnaires at the beginning of the study and at follow up, and completed interviews to understand the impact of the service.

“This the first time automated telephone call technology has been used in the UK in this way,” said Dr Katerina Kassavou from the Department of Public Health and Primary Care at the University of Cambridge. “There is considerable evidence to show that highly tailored interventions are more likely to support patients’ adherence to their prescription regime, which in turn leads to better patient outcomes.”

The IVR application was developed by Simon Edwards, a Communications Specialist from the University Information Service telecoms team at Cambridge.

“Many patients had previous, often negative, experiences with IVR technology, particularly from marketing schemes, so it was important for us to work closely with the research team to understand what patients really wanted,” said Edwards.

“We created a tailored experience which included the preferred delivery method, the timing of calls, and the intervals between repeat calls. The team also researched how the content of the message should change through the month-long trial to maintain patient engagement.”

All recruited patients completed the one-month intervention and follow up interviews. Patients reported that the intervention helped them overcome barriers to taking medications, such as being busy or having many medications to take. They also said it helped them understand the importance of taking medication itself.

Even though the messages were automated, patients also valued the social aspect of the service – especially those patients with lower perceived social support. The IVR service also enabled patients to ask questions, which could be followed up by their doctor or practice nurse later. Patients also recognised it was likely to be more cost-effective to the NHS than a nurse calling them.

The next stage of the work is currently underway. It includes both IVR and text messages and it’s being tested for efficacy in a randomised controlled trial with more than 100 patients recruited by GP practices. The trial is also collecting medical data, i.e. blood pressure and blood sugar, and will also look at the cost effectiveness of the system.

“The early signs are that this digital intervention is well liked by patients and could play an important role in helping patients manage their medicines,” says Dr Kassavou. “We now need to make sure it works in a wider population and to demonstrate that it is a cost-effective intervention.”

The research was funded by the National Institute for Health Research (NIHR) under its School of Primary Care Research and the Research for Patient Benefit programme.

Reference
Kassavou, A et al. Development and piloting of a highly tailored digital intervention to support adherence to anti-hypertensive medications, as an adjunct to primary care consultations. BMJ Open; 4 Jan 2019

A new study has found that London police officers visibly armed with electroshock ‘Taser’ weapons used force 48% more often, and were more likely to be assaulted, than those on unarmed shifts.

However, while use of force can include everything from restraint and handcuffing to CS spray, the Tasers themselves were only fired twice during the year-long study period.

Criminologists from the University of Cambridge say the findings suggest that Tasers can trigger the ‘weapons effect’: a psychological phenomenon in which sight of a weapon increases aggressive behaviour.

While the ‘weapons effect’ has been repeatedly demonstrated in simulated conditions over the last forty years, this is one of the largest studies to show it “in the field” and the first to reveal the effect in law enforcement.

Researchers say their findings, published today in the journal Criminal Justice and Behaviour, may well apply to policing situations in which other forms of weaponry – including the lethal variety – are involved.

“We found that officers are more likely to be assaulted when carrying electroshock weaponry, and more likely to apply force,” said lead researcher Dr Barak Ariel from Cambridge’s Institute of Criminology.

“It is well established that the visual cue of a weapon can stimulate aggression. While our research does not pierce the ‘black box’ of decision-making, the only difference between our two study conditions was the presence of a Taser device.”

“There was no increase in injury of suspects or complaints, suggesting it was not the police instigating hostilities. The presence of Tasers appears to provoke a pattern where suspects become more aggressive toward officers, who in turn respond more forcefully,” he said.

The City of London force is responsible for policing the ‘Square Mile’ business district in the centre of London. It also holds national responsibility for economic crime and prioritises counter-terrorism, violent crime and public order due to its central location.

The force was the first in England and Wales to test “extended deployment” of Tasers – described as “conducted energy devices” in UK policing – to frontline officers. During the rollout, police chiefs allowed Ariel and colleagues to conduct a major experiment.

Between June 2016 and June 2017 the researchers randomly allocated 400 frontline shifts a Taser-carrying officer and compared the results to an equal number of unarmed shifts over the same period. A total of 5,981 incidents occurred during the study.

Use of force by police carrying Tasers was 48% higher than the officers on unarmed shifts. In what researchers call a “contagion effect”, even those unarmed officers accompanying Taser carriers on ‘treatment’ shifts used force 19% more often than those on Taser-free ‘control’ shifts.

Six physical assaults against police were recorded during shifts with Taser-carrying officers, compared to just three on the unarmed ‘control’ shifts. While the numbers are small, assaults against officers are rare, and researchers argue that this doubling is significant.

Despite the increased hostility uncovered by the study, actual use of electroshock weapons was minimal over the study period, with just nine “deholsterings” – only two of which resulted in electric shocks applied to a suspect.

“The City of London police rarely discharged Tasers during the study. Yet the very presence of the weapon led to increased hostility between the police and public,” said Ariel.

The weapons effect was first shown by psychologist Leonard Berkowitz in 1967, in a laboratory experiment involving the administering of electric shocks in the presence of a rifle – an experiment that Ariel points out has been replicated 78 times.

“For many, a weapon is a deterrence. However, some individuals interpret the sight of a weapon as an aggressive cue – a threat that creates a hostile environment,” Ariel said.

“The response is consequently a ‘fight or flight’ dilemma that can result in a behavioural manifestation of aggression and assault. This is what we think we are seeing in our Taser experiment.”

“It would not be surprising to find that serious or violent offenders fit this criteria, especially young males – the very type of suspect that is regularly in direct contact with frontline police.”

Half a million police officers in the United States regularly carry Tasers, and electroshock weapons are now becoming part of frontline policing across the UK.

The study author’s offer a simple solution to bypass the weapons effect: conceal the Tasers. “The relatively inexpensive policy change of keeping Tasers hidden from sight should not limit efficacy, but could reduce the weapons effect we see in the study,” said Ariel.

“This conclusion could be generalised to all types of police armoury, including the lethal firearms carried by police officers. If the presence of weapons can lead to aggression by suspects, so its concealment should be able to reduce aggression and increase officer safety,” he said.

Study co-author Chief Superintendent David Lawes, from the City of London Police, said: “Following the findings of the study, we are exploring whether a simple holster change or weapon position move will nullify the weapons effect issue shown in the experiment. We have also updated our training package for officers carrying Tasers to make them aware of the findings.”

“The use of Tasers have been a proportionate and sensible introduction to policing against a backdrop of unsophisticated terror attacks and an increase in violent crime across London.

“The City of London Police seeks to ensure that any major changes to policy are supported by an evidence base and we wanted to be confident that an extension of Taser deployments to our frontline responders was the right thing to do for both our officers and the public they serve.

“A number of other forces are interested in replicating the study to add to the evidence base and see whether the experiment produces the same results outside of London.

“Across our force, we will continue to use evidence to define how we target problems, which tactics we should use and how we can ensure policing is efficient and safer for both the general public and our officers.”

The robot hand, developed by researchers at the University of Cambridge, was made by 3D-printing soft and rigid materials together to replicate of all the bones and ligaments – but not the muscles or tendons – in a human hand. Even though this limited the robot hand’s range of motion compared to a human hand, the researchers found that a surprisingly wide range of movement was still possible by relying on the hand’s mechanical design.

Using this ‘passive’ movement – in which the fingers cannot move independently – the robot was able to mimic different styles of piano playing without changing the material or mechanical properties of the hand. The results, reported in the journal Science Robotics, could help inform the design of robots that are capable of more natural movement with minimal energy use.

Complex movement in animals and machines results from the interplay between the brain (or controller), the environment and the mechanical body. The mechanical properties and design of systems are important for intelligent functioning, and help both animals and machines to move in complex ways without expending unnecessary amounts of energy.

“We can use passivity to achieve a wide range of movement in robots: walking, swimming or flying, for example,” said Josie Hughes from Cambridge’s Department of Engineering, the paper’s first author. “Smart mechanical design enables us to achieve the maximum range of movement with minimal control costs: we wanted to see just how much movement we could get with mechanics alone.”

Over the past several years, soft components have begun to be integrated into robotics design thanks to advances in 3D printing techniques, which has allowed researchers to add complexity to these passive systems.

The human hand is incredibly complex, and recreating all of its dexterity and adaptability in a robot is a massive research challenge. Most of today’s advanced robots are not capable of manipulation tasks which small children can perform with ease.

“The basic motivation of this project is to understand embodied intelligence, that is, the intelligence in our mechanical body,” said Dr Fumiya Iida, who led the research. “Our bodies consist of smart mechanical designs such as bones, ligaments, and skins that help us behave intelligently even without active brain-led control. By using the state-of-the-art 3D printing technology to print human-like soft hands, we are now able to explore the importance of physical designs, in isolation from active control, which is impossible to do with human piano players as the brain cannot be ‘switched off’ like our robot.”

“Piano playing is an ideal test for these passive systems, as it’s a complex and nuanced challenge requiring a significant range of behaviours in order to achieve different playing styles,” said Hughes.

The robot was ‘taught’ to play by considering how the mechanics, material properties, environment and wrist actuation all affect the dynamic model of the hand. By actuating the wrist, it is possible to choose how the hand interacts with the piano, allowing the embodied intelligence of the hand to determine how it interacts with the environment.

The researchers programmed the robot to play a number of short musical phrases with clipped (staccato) or smooth (legato) notes, achieved through the movement of the wrist. “It’s just the basics at this point, but even with this single movement, we can still get quite complex and nuanced behaviour,” said Hughes.

Despite the limitations of the robot hand, the researchers say their approach will drive further research into the underlying principles of skeletal dynamics to achieve complex movement tasks, as well as learning where the limitations for passive movement systems lie.

“This approach to mechanical design can change how we build robotics,” said Iida. “The fabrication approach allows us to design mechanically intelligent structures in a way that is highly scalable.”

“We can extend this research to investigate how we can achieve even more complex manipulation tasks: developing robots which can perform medical procedures or handle fragile objects, for instance,” said Hughes. “This approach also reduces the amount of machine learning required to control the hand; by developing mechanical systems with intelligence built in, it makes control much easier for robots to learn.”

The research was funded by the Engineering and Physical Sciences Research Council (EPSRC).

Reference:
J.A.E. Hughes, P. Maiolino, F. Iida. ‘An Anthropomorphic Soft Skeleton Hand Exploiting Conditional Models for Piano Playing.’ Science Robotics (2018). DOI: 10.1126/scirobotics.aau3098

The study, published in the journal PLOS Medicine, found that 76% fewer purchases of sugary confectionary, chocolate and potato crisps were bought and eaten ‘on-the-go’ from supermarkets with checkout food policies compared to those without. In addition, 17% fewer small packages of these items were bought and taken home from supermarkets immediately after introducing a checkout food policy.

Large supermarket chains such as Tesco, Asda and Sainsbury’s have captured the majority of the grocery market and play a major role in shaping food preferences and purchasing behaviour. Retail practices such as product displays, positioning, promotions and pricing can all influence consumers’ choices in stores.

Supermarket checkouts provide a unique location for prompting purchases as all customers have to pass through them to pay and may spend considerable time in queues; however, the majority of food at supermarket checkouts could be considered unhealthy. Over the last decade, many UK supermarket groups have made voluntary commitments to remove or limit unhealthy foods at the tills or to provide healthier options.

“Many snacks picked up at the checkout may be unplanned, impulse buys – and the options tend to be confectionary, chocolate or crisps,” says Dr Jean Adams from the Centre for Diet and Activity Research at the University of Cambridge. “Several supermarkets have now introduced policies to remove these items from their checkouts, and we wanted to know if this had any impact on people’s purchasing choices.”

To examine the effect that the introduction of checkout food policies in major supermarket chains has had on shoppers’ purchasing habits, Dr Adams led a team of researchers at the universities of Cambridge, Stirling and Newcastle who analysed data from the Kantar Worldpanel’s Consumer panel for food, beverages and household products. Six out of the nine major supermarkets introduced checkout food policies between 2013 and 2017. (The researchers anonymised the information to avoid ‘naming and shaming’ companies.)

Firstly, the team looked at how purchases of less healthy common checkout foods brought home changed following the implementation of checkout policies. They used data from over 30,000 UK households from 12 months before to 12 months after implementation.

The researchers found that implementation of a checkout food policy was associated with an immediate 17% reduction in purchases. After a year, shoppers were still purchasing over 15% fewer of the items compared to when no policy was in place.

Next, they looked at data from 7,500 shoppers who recorded food bought and eaten ‘on-the-go’ during 2016-17 from supermarkets with and without checkout food policies. On-the-go purchases are often impulsive and can be the result of children pestering their parents. The researchers found that shoppers made 76% fewer annual purchases of less healthy common checkout foods from supermarkets with checkout food policies compared to those without.

As the study was not a randomised control trial, it was not possible to say definitely that the changes in purchasing behaviour were due to the checkout food policies. Stores that chose to have checkout food policies may have been different from those that did not. Or shoppers may have changed to purchasing larger packages from the same stores, or similar products from stores that aren’t supermarkets.

“Our findings suggest that by removing sweets and crisps from the checkout, supermarkets can have a positive influence on the types of purchases their shoppers make,” says Dr Katrine Ejlerskov, the study’s first author. “This would be a relatively simple intervention with the potential to encourage healthier eating. Many of these purchases may have been impulse buys, so if the shopper doesn’t pick up a chocolate bar at the till, it may be one less chocolate bar that they consume.”

“It may seem obvious that removing unhealthy food options from the checkout would reduce the amount that people buy, but it is evidence such as this that helps build the case for government interventions to improve unhealthy behaviours,” adds Dr Adams.

“One such intervention might be to introduce nutritional standards for checkout food as suggested in the Government’s recent Childhood Obesity Plan. Such a government-led policy might prove attractive to supermarkets as it would provide a level playing field across the sector.”

The work was undertaken by the authors as part of the Public Health Research Consortium. The Public Health Research Consortium is funded by the Department of Health and Social Care Policy Research Programme.

Reference
Ejlerskov, KT et al. Supermarket policies on less healthy food at checkouts: natural experimental evaluation using interrupted time series analyses of purchases. PLOS Medicine; 18 Dec 2018; DOI: 10.1371/journal.pmed.1002712

Built on land adjacent to Addenbrooke’s and the Rosie Hospitals, the children’s hospital will bring together some of the world’s top scientists to explore new ways of diagnosing and treating some of the most challenging diseases of childhood. Mapping the whole human genome and understanding the genetic basis of disease and recovery is central to the hospital’s vision. It aims to make an important contribution globally to the development of children’s healthcare while providing world class care for families in the east of England.

The project is a partnership involving Cambridge University Hospitals (CUH) NHS Foundation Trust, Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge. The development is a major part of the strategy to invest in world class facilities led by the Sustainability and Transformation Partnership for Cambridgeshire and Peterborough.

The Vice-Chancellor of the University of Cambridge, Professor Stephen Toope, said: “The announcement from the Secretary of State is extremely positive. It is not only an investment in the research and clinical expertise in Cambridge but, importantly, it is an investment in the future of our children and young people. By helping us to improve how we treat those young people unfortunate enough to be affected by serious childhood diseases, the new hospital  has the potential to transform the provision of healthcare for families in the East of England.”

Patrick Maxwell, Regius Professor of Physic and Head of the School of Clinical Medicine, said: “This is a welcome and very significant investment from the government. The new children’s hospital will bring together clinical and research expertise from across Cambridge, enabling us to make a major difference to the health of young people across the East of England and, through our research, throughout the UK and beyond.”

Professor David Rowitch from the Department of Paediatrics at the University of Cambridge added: “It is time to bridge the divide between physical and mental health and move away from silo working. With strengths across the board from genomics to complex medical care, child and adolescent psychiatry, Cambridge is perfectly positioned to lead by example.”

The announcement has also been welcomed by the chief executives of the two NHS trusts involved. Roland Sinker, CUH chief executive, described the announcement as “a tribute to our outstanding staff who care for very poorly children day in day out in facilities that currently are not reflecting the world class service we provide”. Tracy Dowling, chief executive of Cambridgeshire and Peterborough NHS Foundation Trust, which provides mental health services for young people and adults as well as physical health services for older people and those with long-term conditions, said the new hospital would provide “the most incredible opportunity” to bring together physical and mental health services under one roof.

Adapted from a news story from CUH.

Now, in a study involving marmosets, scientists at the University of Cambridge have identified the region of the brain that contributes to this phenomenon, and shown that the experimental antidepressant ketamine acts on this region, helping explain why this drug may prove effective at treating anhedonia.

Depression is a common and debilitating condition which is recognised as a leading cause of disability worldwide. A survey published in 2016 found that 3.3 out of every 100 UK adults had experienced depression in the week before being interviewed.

A key symptom of depression is anhedonia, typically defined as the loss of ability to experience pleasure. However, anhedonia also involves a lack of motivation and lack of excitement in anticipation of events. All these aspects have proven difficult to treat. One major issue slowing down progress in developing new treatments is that the brain mechanisms that give rise to anhedonia remain largely unknown.

“Imaging studies of depressed patients have given us a clue about some of the brain regions that may be involved in anhedonia, but we still don’t know which of these regions is causally responsible,” says Professor Angela Roberts from the Department of Physiology, Development and Neuroscience at the University of Cambridge.

“A second important issue is that anhedonia is multi-faceted – it goes beyond a loss of pleasure and can involve a lack of anticipation and motivation, and it’s possible that these different aspects may have distinct underlying causes.”

In fact, even when existing therapies do work, the reasons why they are effective are not always clear, making it difficult to target these therapies to individuals.

Using marmosets, a type of non-human primate, Professor Roberts and MBPhD student Laith Alexander, along with other colleagues, including those at the Wolfson Brain Imaging Centre and Translational Neuroimaging Laboratory, have shown how over-activity in a specific area of the brain’s frontal lobe blunts the excitement seen when anticipating a reward and the motivation to work for that reward. Their results are published today in the journal Neuron.

In the present study marmosets were trained to respond to two sounds: if they heard sound A, they would receive a treat of marshmallows; if they heard sound B, they would not receive a treat. Once they had learned the association, they would become aroused at sound A, reflected in an increase in blood pressure and excited movements of the head. They would not show the same response to B.

The researchers then infused either a drug or a saline solution into a region of the brain known as ‘area 25’ through thin cannulae (metal tubes) in the marmosets’ head. Cannulae are inserted during a single surgical procedure, and once the anaesthetic has worn off they do not trouble the animals.

The effect of the drug was to temporarily make this particular brain region over-active, and this resulted in the marmosets showing less excitement and anticipation at the prospect of a marshmallow treat. They were however as quick to eat the marshmallow treat as before. The saline infusion made no difference to the activity in area 25 or to the marmosets’ excitement and anticipation.

In a second task, the marmosets had to make more and more responses to get their reward – while initially they would receive a marshmallow treat after pressing a coloured shape on a touch sensitive computer screen just once, as the task proceeded, they would be required to press the coloured shape an increasing number of times. Eventually, the marmoset would reach a point where it gave up, considering the treat to be no longer worth the effort required.

When the marmosets’ area 25 was over-activated, the researchers observed that the marmosets gave up much faster. This lack of motivation is another key symptom associated with anhedonia.

By using PET scanning techniques to observe activity across the marmoset’s brain the researchers found that over-activity in area 25 had a knock-on effect to other brain regions, which also became more active, indicating that these were all part of brain circuity controlling anticipatory excitement.

Finally, the researchers investigated the effect of the experimental antidepressant, ketamine. Marmosets were given the antidepressant 24 hours ahead of the experiment. This time, even when marmosets were administered the treatment to make area 25 over-active, they still showed excitement and anticipation at the marshmallow reward. PET scanning revealed that the brain circuits were functioning normally. In other words, ketamine had blocked the effects of over-activating area 25, which would otherwise blunt anticipation.

“Understanding the brain circuits that underlie specific aspects of anhedonia is of major importance, not only because anhedonia is a core feature of depression but also because it is one of the most treatment-resistant symptoms,” says Laith Alexander, the study’s first author.

“By revealing the specific symptoms and brain circuits that are sensitive to antidepressants like ketamine, this study moves us one step closer to understanding how and why patients may benefit from different treatments.”

Marmosets are used to study brain disorders such as depression because of the similarity of the frontal lobes to those of humans. Rats, which are often used in psychology studies, have frontal lobes quite different to those of humans, making it less easy to translate studies of frontal lobe circuitry directly into the clinic.

“Depression affects many millions of people worldwide, so it’s important we get to the problems within the brain that underlie the various symptoms,” says Professor Roberts. “Studying these symptoms in non-human primates, such as marmosets can help bridge the gap between findings from rodent studies and the clinic.

“Using marmosets, we are able to manipulate the activity in specific brain regions, helping us see which regions are causally involved. These effects are temporary, and wear off after a short time.”

The research was funded by Wellcome.

Reference
Alexander, L, et al. Fractionating blunted reward processing characteristic of anhedonia by over-activating primate subgenual anterior cingulate cortex. Neuron; 4 Dec 2018; DOI: 10.1016/j.neuron.2018.11.021

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Many pregnancies fail because the embryo does not implant correctly into the lining of the womb (uterus) and fails to form a placental attachment to the mother. Yet, because of the complexities of studying this early period of our development, very little is understood about what is happening normally and what can go wrong. Animals are too dissimilar to humans to provide a good model of placental development and implantation.

“The placenta is absolutely essential for supporting the baby as it grows inside the mother,” says Dr Margherita Turco, the study’s first author, from the Departments of Pathology and Physiology, Development and Neuroscience at the University of Cambridge. “When it doesn’t function properly, it can result in serious problems, from pre-eclampsia to miscarriage, with immediate and lifelong consequences for both mother and child. But our knowledge of this important organ is very limited because of a lack of good experimental models.”

Efforts to grow human placental cells started over 30 years ago in the Pathology department where Professors Ashley Moffett and Charlie Loke were studying cellular events in the first few weeks of pregnancy.  With their chief technician, Lucy Gardner, they found ways to isolate and characterise placental trophoblast cells.  These techniques, combined with the organoid culture system, enabled the generation of miniature functional models of the early placenta – or ‘mini-placentas’.

In the past few years, a new field of research has blossomed that uses these organoids – often referred to as ‘mini-organs’ – enabling insights into human biology and disease. At the University of Cambridge, one of the world leaders in organoid research, scientists are using organoid cultures to grow everything from ‘mini-brains’ to ‘mini-livers’ to ‘mini-lungs’.

In a study funded by Wellcome and the Centre for Trophoblast Research, the Cambridge team was able to grow organoids using cells from villi – tiny frond-like structures – taken from placental tissue. These trophoblast organoids are able to survive long-term, are genetically stable and organise into villous-like structures that secrete essential proteins and hormones that would affect the mother’s metabolism during the pregnancy. Further analysis showed that the organoids closely resemble normal first-trimester placentas. In fact, the organoids so closely model the early placenta that they are able to record a positive response on an over-the-counter pregnancy test.

Professor Graham Burton, a co-author and Director of the Centre for Trophoblast Research, which last year celebrated its tenth anniversary, says: “These ‘mini-placentas’ build on decades of research and we believe they will transform work in this field. They will play an important role in helping us investigate events that happen during the earliest stages of pregnancy and yet have profound consequences for the life-long health of the mother and her offspring. The placenta supplies all the oxygen and nutrients essential for growth of the fetus, and if it fails to develop properly the pregnancy can sadly end with a low birthweight baby or even a stillbirth.”

In addition, the organoids may shed light on other mysteries surrounding the relationships between the placenta, the uterus and the fetus: why, for example, is the placenta able to prevent some infections passing from the mother’s blood to the fetus while others, such as Zika virus, are able to pass through this barrier? The organoids may also be used for screening the safety of drugs to be used in early pregnancy, to understand how chromosomal abnormalities may perturb normal development, and possibly even provide stem cell therapies for failing pregnancies.

Last year, the same team supported by Cambridge’s Centre for Trophoblast Research reported growing miniature functional models of the uterine lining.

“Now that we’ve developed organoid models of both sides of the interface – maternal tissue and placental tissue – we can start to look at how these two sides talk to each other,” adds Professor Ashley Moffett.

Professor Moffett also co-directed a recent study published in Nature that used genomics and bioinformatics approaches to map over 70,000 single cells at the junction of the uterus and placenta. This study revealed how the cells talk to each other to modify the immune response and enable the pregnancy, presenting new and unexpected cell states in the uterus and placenta, and showing which genes are switched on in each cell.

References

Turco, MY et al. Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature; 28 Nov 2018; DOI: 10.1038/s41586-018-0753-3​

Vento-Tormo, R, et al. Single-cell reconstruction of the early maternal–fetal interface in humans. Nature; 14 Nov 2018; DOI: 10.1038/s41586-018-0698-6​

Stabbed by a lover with a fish-gutting knife. Beaten to death for littering with eel skins. Shot with an arrow during a student street brawl. Shanked by a sore loser after late-night backgammon.

These were just some of the ways to die violently in the city of London during the 14th century, as catalogued in the ‘Coroners’ Rolls’: the records of the medieval official tasked with documenting sudden and unnatural death – whether accident, suicide or homicide.

Now, University of Cambridge criminologist Professor Manuel Eisner has plotted all cases of murder from the surviving rolls – covering the years 1300 to 1340 – onto a digital map of the old city to show for the first time the ‘hot spots’ of lethal violence in medieval London.

Building on work conducted by the historian Barbara Hannawalt over forty years ago, Eisner has also produced an analysis of the 142 homicides committed within the city’s boundaries to reveal not just locations but the days, times and favoured methods.

The “murder map” of medieval London will be made publicly available on Wednesday on the website of the Violence Research Centre, which will also host a launch event today at the Institute of Criminology.

“Following notification of a violent death, the Coroner and Sheriffs would summon a jury from the local area to investigate, then record all the findings,” said Eisner.

“The events described in the Coroners’ Rolls show weapons were never far away, male honour had to be protected, and conflicts easily got out of hand. They give us a detailed picture of how homicide was embedded in the rhythms of urban medieval life.”

“By digitally mapping these murder cases, we hope to create an accessible resource for the public to explore these remarkable records,” he said.

Eisner’s map allows people to filter the killings by year, weapon and crime scene, and has updated the language of each case description for modern audiences.

While the map shows murders occurred across the city, two main homicide ‘hot spots’ emerge, both commercial centres of the time. One was the stretch of Cheapside from St Mary-le-Bow church – the ‘bow bells’ of cockney legend – leading up to St Paul’s Cathedral.

The other was further east: the triangle of Gracechurch, Lombard (then ‘Langbourn’) and Cornhill streets that radiate out from Leadenhall market, the history of which can be traced back to the 14th century.

The majority of murders, some 68%, took place in London’s busy streets and markets, with 21% occurring in private residences. Religious buildings (six murders) may have been more dangerous than brothels (two murders).

As today, medieval homicide was a weekend activity, with almost a third (31%) of murders taking place on a Sunday. “Sunday was the day when people had time to engage in social activities, such as drinking and gaming, which would often trigger frictions that led to assault,” said Eisner.

Around 77% of the murders were committed between early evenings, “around the hour of vespers”, and the first hours after curfew. Daggers and swords dominate the list of murder weapons, used in 68% of all cases. Thick ‘quarter staff’ poles designed for close combat were used in 19% of cases.

Almost all (92%) perpetrators were men. In just four cases a woman was the only suspect. About a third of the cases had more than one suspect, with a number of killings involving brothers or servants helping masters.

Estimates for London populations in the 14th century range from 40,000 to 100,000. Assuming a city of 80,000, Eisner suggests that medieval London murder rates were about 15-20 times higher than we would expect to see in a contemporary UK town of equivalent size.

However, he argues that comparisons with modern society are problematic. “We have firearms, but we also have emergency services. It’s easier to kill but easier to save lives.”

In fact, death by murder could be a slow process in the 14th century. “Over 18% of victims survived at least a week after the initial trauma, probably dying eventually from infections or blood loss,” said Eisner.

One saddle-maker who had his fingers cut off by a rival died of his wounds – and consequently became a homicide victim – a full three weeks later.

While his work takes in everything from bullying prevention to youth crime, violence reduction across the centuries is a major research strand for Prof Eisner. He has studied long-term historical trends in homicide from 1000AD onwards.

“London in the decades before the Black Death had more homicides relative to the population than London in the 18th or 19th century,” added Eisner.

“The trend in London is in line with the long-term decline of homicide found across cities in Western Europe, a decline that led to the pacified spaces that were essential for the rise of urban life and civility in Europe.”

The system, called LION LBD and developed by computer scientists and cancer researchers at the University of Cambridge, has been designed to assist scientists in the search for cancer-related discoveries. It is the first literature-based discovery system aimed at supporting cancer research. The results are reported in the journal Bioinformatics.

Global cancer research attracts massive amounts of funding worldwide, and the scientific literature is now so huge that researchers are struggling to keep up with it: critical hypothesis-generating evidence is now often discovered long after it was published.

Cancer is a complex class of diseases that are not completely understood and are the second-leading cause of death worldwide. Cancer development involves changes in numerous chemical and biochemical molecules, reactions and pathways, and cancer research is being conducted across a wide variety of scientific fields, which have variability in the way that they describe similar concepts.

“As a cancer researcher, even if you knew what you were looking for, there are literally thousands of papers appearing every day,” said Professor Anna Korhonen, Co-Director of Cambridge’s Language Technology Lab who led the development of LION LBD in collaboration with Dr Masashi Narita at Cancer Research UK Cambridge Institute and Professor Ulla Stenius at Karolinska Institutet in Sweden. “LION LBD uses AI to help scientists keep up-to-date with published discoveries in their field, but could also help them make new discoveries by combining what is already known in the literature by making connections between sources that may appear to be unrelated.”

The ‘LBD’ in LION LBD stands for Literature-Based Discovery, a concept developed in the 1980s which seeks to make new discoveries by combing pieces of information from disconnected sources. The key idea behind the original version of LBD is that concepts that are never explicitly linked in the literature may be indirectly linked through intermediate concepts.

The design of the LION LBD system allows real-time search to discover indirect associations between entities in a database of tens of millions of publications while preserving the ability of users to explore each mention in its original context.

“For example, you may know that a cancer drug affects the behaviour of a certain pathway, but with LION LBD, you may find that a drug developed for a totally different disease affects the same pathway,” said Korhonen.

LION LBD is the first system developed specifically for the needs of cancer research. It has a particular focus on the molecular biology of cancer and uses state-of-the-art machine learning and natural language processing techniques, in order to detect references to the hallmarks of cancer in the text. Evaluations of the system have demonstrated its ability to identify undiscovered links and to rank relevant concepts highly among potential connections.

The system is built using open data, open source and open standards, and is available as an interactive web-based interface or a programmable API.

The researchers are currently working on extending the scope of LION-LBD to include further concepts and relations. They are also working closely with cancer researchers to help and improve the technology for end users.

The system was developed in collaboration with University of Cambridge Language Technology Lab, Cancer Research UK Cambridge Institute, and Karolinska Institutet in Sweden, and was funded by the Medical Research Council.

Reference:
Sampo Pyysalo et al. ‘LION LBD: a Literature-Based Discovery System for Cancer Biology.’ Bioinformatics (2018). DOI: 10.1093/bioinformatics/bty845