The strategy of using people’s need for healthcare against them by violently denying access sets a dangerous precedent that the global health community must urgently address, say an international team of researchers.

The authors of a new report published today (15 March) in The Lancet– marking six years since the conflict began – have “triangulated” various data sources to provide new estimates for the number of medical personnel killed so far: 814 from March 2011 to February 2017.

However, they also say this is likely to be a “gross underestimate” due to limitations of evidence-gathering and corroboration in the conflict areas.  

There were 199 attacks on health facilities in 2016 alone – an increase from 91 in 2012, when the Syrian government effectively criminalised medical aid for the opposition. The government and its allies, including Russia, have been responsible for at least 94% of attacks, say the experts – threatening the foundation of medical neutrality.

Besieged areas are denied medicine, and remaining medics are delivering what care they can in brutal conditions. Despite explicit protections under International Humanitarian Law, attacks on health workers have included imprisonment, abduction, torture and execution.  

The authors of the latest report, including researchers from Cambridge’s departments of sociology and politics, say the conflict has exposed serious shortcomings in global governance.

They call for the systematic documentation of attacks on health workers and, critically, the perpetrators via the WHO, allowing for greater accountability. UN policies and practices should also be reviewed and strengthened, including operational capacity to deliver support to health workers across conflict lines.

The research team also calls for global solidarity with health workers in the Syrian conflict, including support to increase awareness among donors and politicians.

“Syria has become one of the most dangerous places on earth to be a healthcare worker,” says Dr Adam Coutts, report co-author from Cambridge’s Department of Sociology.

“Thousands of health workers have left and relocated to neighbouring countries and further afield such as Europe. This poses significant challenges for current healthcare provision in Syria but also for future health system rebuilding in a post conflict situation.”

Between 2011 and 2015, it is estimated that 15000 doctors, or half of the pre-war numbers, left the country. In Eastern Aleppo, approximately 1 doctor remained for every 7000 residents, compared with 1 in 800 in 2010.

The exodus of older, experienced doctors has left critical gaps. Younger, less experienced physicians – many of whom are students with no experience in trauma management or emergency medicine – have become indispensable. However, this increases risk for patients and warns of a serious shortage of skilled doctors in future.

In non-government controlled areas, the few health workers left face massive numbers of trauma victims, shortages of medicines, epidemics of infectious disease and chemical attacks. In areas under siege, surgical supplies and essential medicines are seldom allowed in, patients rarely evacuated, and public health measures such as water chlorination and measles vaccination are sometimes blocked.

The bulk of Syria’s remaining health workers are in government-controlled areas, where they also face mortar attacks from rebel areas and travel restrictions. Some report being forced to breach ethical principles under pressure.

Sophie Roborgh, one of the report’s authors from the Department of Politics and International Studies, conducts research on violence against health workers and medical infrastructure in conflict, and how health workers deal with it – professionally and personally.

“Healthcare workers that remain have been forced to adjust their entire lives around the threats and pressures they face,” she says. “There is such a shortage of staff that some physicians and other medical staff actually live full-time in hospitals.

“One medic showed me pictures on his phone of his colleague’s young children, who spend much time with their father, helping to mop up blood in operation rooms. Another told me how he celebrated his wedding in the hospital.

“We are trying to uncover which measures of support for these health workers are actually effective, in the hope that we can eventually move beyond a one-size-fits-all approach to a more specific, evidence-based model for conflict situations.”

Coutts says that practical policy options to assist displaced Syrian healthcare workers require evidence of where they are and what skills and training capacities they have. This information is not currently available and is badly needed.   

“It is vital that the international community design policies and interventions to help displaced healthcare workers find and sustain employment in neighbouring host countries,” says Coutts.  

“Due to visa and right-to-work issues, Syrian doctors and allied health professionals are unable to practice in countries such as Lebanon and Jordan. This is currently an untapped and essential workforce that could be used to support the already overstretched humanitarian response and public services in host communities.”

Researchers studying a deal in which Google’s artificial intelligence subsidiary, DeepMind, acquired access to millions of sensitive NHS patient records have warned that more must be done to regulate data transfers from public bodies to private firms.

The academic study says that “inexcusable” mistakes were made when, in 2015, the Royal Free NHS Foundation Trust in London signed an agreement with Google DeepMind. This allowed the British AI firm to analyse sensitive information about 1.6 million patients who use the Trust’s hospitals each year.

The access was used for monitoring software for mobile devices, called Streams, which promises to improve clinicians’ ability to support patients with Acute Kidney Injury (AKI). But according to the study’s authors, the purposes stated in the agreement were far less specific, and made more open-ended references to using data to improve services.

More than seven months after the deal was put in place, an investigation by New Scientist then revealed that DeepMind had gained access to a huge number of identifiable patient records and that it was not possible for the public to track how these were being used. They included information about people who were HIV-positive, details about drug overdoses and abortions, and records of routine hospital visits.

As of November 2016, DeepMind and the Trust have replaced the old agreement with a new one. The original deal is being investigated by the Information Commissioner’s Office (ICO), which has yet to report any findings publicly. The National Data Guardian (NDG) is also continuing to look into the arrangement. DeepMind retained access to the data that it had been given even after the ICO and NDG became involved, and the app is being deployed.

Both the Trust and DeepMind have disputed the findings in the new study. In a joint response they claimed that the paper misrepresented the NHS’s use of technology to process data and also that the analysis contained several errors. They stressed that the Streams app was making a significant difference to hospital staff, and highlighted its life-saving potential.

The authors, however, said that these accusations of factual inaccuracy and analytical error were unsubstantiated, and that their article makes clear why the agreement is unusual and in the public interest.

The study reviews the original agreement in depth, with a systematic synthesis of publicly available documentation, statements, and other details obtained by Freedom of Information requests. It was carried out by Dr Julia Powles, a Research Associate in law and computer science at St John’s College, University of Cambridge, and Hal Hodson, who broke the New Scientist story and is now Technology Correspondent for The Economist.

Both authors say that it is unlikely that DeepMind’s access ever represented a data security risk, but that the terms were nonetheless highly questionable, in particular because they lacked transparency and suffered from an inadequate legal and ethical basis for Trust-wide data access.

They say the case should be a “cautionary tale” for the NHS and other public institutions, which are increasingly seeking tech companies’ help to improve services, but could, in the process, surrender substantial amounts of sensitive information, creating “significant power asymmetries between citizens and corporations”.

“Data analytics and machine learning in general offer promise in improving healthcare and clearly digital technology companies will have a role to play,” Powles said. “To the extent that it signals a move in this direction, we think that there were inadequacies in the case of this particular deal.”

“The deal betrays a level of naivety regarding how public sector organisations set up data-sharing arrangements with private firms, and it demonstrates a major challenge for the public and public institutions. It is worth noting, for example, that in this case DeepMind, a machine learning company, had to make the bizarre promise that it would not yet use machine learning, in order to engender trust.”

Powles and Hodson argue that the transfer of data to DeepMind did not proceed as it should have, questioning in particular its invocation of a principle known as “direct care”. This assumes that an “identified individual” has given implied consent for their information to be shared for uses that involve the prevention, investigation, or treatment of illness.

No patient whose data was shared with DeepMind was ever asked for their consent. Although direct care would clearly apply to those monitored for AKI, the records that DeepMind received covered every other patient who used the Trust’s hospitals. These extended to people who had never been tested or treated for kidney injuries, people who had left the catchment area, and even some who had died.

In fact, the authors note that, according to the Royal Free and DeepMind’s own announcements, only one in six of the records DeepMind accessed would have involved AKI patients. For a substantial number of patients, therefore, the relationship was indirect. As a result, special permissions should have been sought from the Government, and agencies such as the ICO and NDG should have been consulted. This did not happen.

Such applications of “direct care” have been queried before. In December 2016, Dr Alan Hassey of the NDG, which provides national guidance on the use of confidential information, wrote that: “an erroneous belief has taken hold in some parts of the health and care system that if you believe what you are doing is direct care, you can automatically share information on a basis of implied consent”. Dr Hassey noted that direct care is not “of itself a catch-all… The crucial thing is that information sharing must be in line with the reasonable expectations of the individual concerned”.

The researchers’ survey also criticises the lack of transparency in the agreement, pointing out that neither party made clear the volume of data involved, nor that it involved so many identifiable records. How that data has been, and is being, used, has never been independently scrutinised. Last week, DeepMind announced plans to develop a new data-tracking system, to make such processes more transparent, at an unspecified future stage.

The authors liken the relationship overall to a one-way mirror. “Once our data makes its way onto Google-controlled servers, our ability to track it – to understand how and why decisions are made about us – is at an end,” they write.

The paper says that an obvious lesson is that no such deal should be launched without full disclosure of the framework of documents and approvals which underpins it. In light of the 2013 Caldicott review of sharing of patient information, they write that: “The failure of both sides to engage in any conversation with patients and citizens is inexcusable.”

They also suggest that private companies should have to account for their use of public data to properly-resourced and independent bodies. Without this, they argue that tech companies could gradually gain an unregulated monopoly over health analytics.

“The reality is that the exact nature and extent of Google’s interests in NHS patient data remain ambiguous,” the authors add. Powles notes that while Google has no stated plans to exploit the data for advertising and other commercial uses, its unparalleled access to such information, without any meaningful oversight, does not rule out the possibility in future.

“I personally think that because data like this can get out there, we are almost becoming resigned to the idea,” Powles added. “This case stresses that we shouldn’t be. Before public institutions give away longitudinal data sets of our most sensitive details, they should have to account to a comprehensive, forward-thinking and creative regulatory system.”

A spokesman for both the Royal Free London and DeepMind said that both organisations were “committed to working together to support world class care for patients”. He added: “Every trust in the country uses IT systems to help clinicians access current and historic information about patients under the same legal and regulatory regime.”

Powles and Hodson are working on a second paper, analysing the terms of the revised DeepMind-Royal Free arrangement since November 2016 and the ongoing regulatory investigations. Their current study is published in the journal Health and Technology. 

Without nature, humans could be neither healthy nor happy. And yet the natural world can be completely ransacked without causing even a tiny blip on our usual measures of economic progress or poverty.

A major UN environmental meeting recently looked at launching an assessment of the different values that people attribute to nature, and what nature contributes to human societies. However, these high level discussions will be futile unless our measures of societal progress expand to explicitly include what nature does for human well-being and prosperity, especially for poor people.

Nature matters to people’s well-being in many different ways. It obviously provides us with basic needs such as food, clean air and water, as well as protection from environmental hazards. There is also a clear relationship with both physical and mental well-being, especially for those who are fortunate enough to have access to green spaces.

Beyond these instrumental roles, there is also evidence from around the world that nature is a more fundamental contributor to people’s sense of self. It is an integral part of what constitutes well-being, captured for some in the awe-inspiring moments when standing on top of a mountain, the breath-taking view of a beautiful river, or in the feeling of freedom associated with traversing a wide open landscape.

The problem with economic indicators

Despite the value we get from nature, our measures of progress and well-being remain much narrower, focused on what is visible and measurable. Gross Domestic Product (GDP) has been the most prominent approach since the end of World War II, with GDP seen as a useful snapshot of the state of the economy and people’s well-being. What these figures often hide are those things, like the role of nature, that are not measured in the monetary economy, but are an important part of daily life and can be crucial for sustaining future prosperity.

There are alternatives. One that has gained some momentum is the Inclusive Wealth Index, which takes into account broader measures of human and natural well-being – its most recent assessment suggested that conventional GDP figures had greatly exaggerated growth over the period 1992-2010. In international development, the UN’s Human Development Index and the “multidimensional poverty index” both recognise a larger set of issues, combining material standards with measures of health and education. But they still do not adequately incorporate the role of nature.

Ignoring nature creates some perverse paradoxes. Measured GDP might actually increase as a consequence of a major environmental disaster, because of the economic activity created by the clean up and repair. Meanwhile, the environmental losses themselves don’t show up in economic measures. A country could get rich by cutting down all its primary forests (and many have), but the associated loss of habitat and wild species would not feature in national accounts.

Governments continue to make decisions based on a key set of headline figures. These include GDP and per capita income, which reflect economic prosperity, and, in poorer countries, the extent and incidence of poverty. But we can do better: our ongoing research focuses on developing environmentally-adjusted measures of multidimensional poverty, based on the insight that people are typically poorer when they do not have access to nature.

Our research suggests that failing to consider these missing environmental aspects can result in an incomplete assessment of the multiple dimensions and underlying drivers of poverty. Consequently, the identification of the poor, as well as an understanding of what makes them poor, risks being partial, thereby posing a challenge to addressing poverty adequately.

The current status quo fails people, especially the poor, and also threatens future prosperity by undervaluing nature. Those who benefit from the current approaches are typically global elites who profit from environmental destruction (which goes unrecognised).

The losers are those most dependent on nature for their livelihoods and those especially vulnerable to environmental change. Even if nature is valued, it is typically converted into money equivalents, which favours those who are able and willing to parcel out nature into small commoditised bundles, which can then be sold to the highest bidder. This fails to take into account the views of those who believe that nature matters in other ways or in its own right, who care about the beauty of nature and the sheer joy that it provides to many.

The consequences of neglecting people’s varied views and aspirations have become apparent from recent political events in Europe and the US. Nature matters to our well-being, and people see their relationship with nature in many different ways. Recognising this is a crucial step towards building a more inclusive, equitable and sustainable society.

Judith Schleicher, Postdoctoral Researcher in Conservation, Poverty and Wellbeing, University of Cambridge and Bhaskar Vira, Reader in Political Economy at the Department of Geography and Fellow of Fitzwilliam College; Director, University of Cambridge Conservation Research Institute, University of Cambridge

This article was originally published on The Conversation. Read the original article.

A survey by Nature revealed that 52% of researchers believed there was a “significant reproducibility crisis” and 38% said there was a “slight crisis”.

We asked three experts how they think the situation could be improved.

Open Research is the answer

Danny Kingsley, head of the Office of Scholarly Communication, University of Cambridge

The solution to the scientific reproducibility crisis is to move towards Open Research– the idea that scientific knowledge of all kinds should be openly shared as early as it is practical in the discovery process. We need to reward the publication of research outputs along the entire process, rather than just each journal article as it is published.

As well as other research outputs – such as data sets – we should reward research productivity itself as well as the thought process and planning behind the study. This is why Registered Reports was launched in 2013, where researchers register the proposal and how the research will be conducted, before any experimental work commences. It allows editorial decisions to be based on the rigour of the experimental design and increases the likelihood that the findings could be replicated.

In the UK there is now a requirement from most funders that the data underpinning a research publication is made available. However, although there are moves towards open research, many argue against the sharing of data among the research community.

Researchers often write multiple papers from a single data set and many fear that if this data is released with the first publication then the researcher will be “scooped” by another research group, who will publish findings from similar data sets before the original authors get the chance to publish follow up articles – to gain maximum credit for the work. If the publication of data itself could be recorded as a “research output”, then being scooped would no longer be such an issue, as such credit will have been given.

One benefit of sharing data could be an improvement in its quality – as previous research has shown. And there have been small steps towards this goal, such as a standard method of citing data.

We also need to publish “null” results – those that do not support the hypothesis – to prevent other researchers wasting time repeating work. There are a few publication outlets for this, and a recent press release from ResearchGate indicated that it supports the sharing of failed experiments through its “project” offering. It lets users upload and track experiments as they are happening – meaning no one knows how they will turn out.

Psychology is leading the way out of crisis

Jim Grange, senior lecturer in psychology, Keele University

To me, it is clear that there is a reproducibility crisis in psychological science, and across all sciences. Murmurings of low reproducibility began in 2011 – the “year of horrors” for psychology – with a high profile fraud case. But since then, The Open Science Collaboration has published the findings of a large-scale effort to closely replicate 100 studies in psychology. Only 36% of them could be replicated.

The incentive structures in universities and the attitude that you “publish or perish” means that researchers prioritise “getting it published” over “getting it right”. It also means that some, implicitly or explicitly, use questionable research practices to achieve publication. These may include failing to report parts of data sets or trying different analytical approaches to make the data fit what you want to say. It could also mean presenting exploratory research as though it was originally confirmatory (designed to test a specific hypothesis).

However, many psychology journals now recommend or require the preregistration of studies which allow researchers to detail their predictions, experimental protocols, and planned analytical strategy before data collection. This provides confidence to readers that no questionable research practices have occurred.

Registered Reports has taken this further. But of course, once results are produced, isolated findings don’t mean much until they have been replicated.

I make efforts to replicate results before trying to publish and you’d be forgiven for thinking that replication attempts are common in science, but this is simply not the case. Journals seek novel theories and findings, and view replications as treading over old ground which offers little incentive for career-minded academics to conduct replications.

This has also led to the introduction of Registered Replication Reports in Perspectives on Psychological Science. This is where teams of researchers each follow identical procedures independently and aim to replicate important findings from the literature. A single paper then collates and analyses them to establish the size and reproducibility of the original study.

Although psychology is leading the way for improvements with these pioneering initiatives, it is certainly not out of the woods. But it has started to move beyond a crisis and make impressive strides – more disciplines need to follow suit.

This is a publication bias crisis

Ottoline Leyser, director of the Sainsbury Laboratory, University of Cambridge

Reproducibility is a fundamental building block of science. If two people do the same experiment, they should get the same result. But there are many good reasons why two “identical” experiments might not give the same result such as unknown differences that have not been considered – and some exciting discoveries have been made this way.

So if a lack of reproducibility is itself not necessarily a problem, why is everybody talking about a crisis? In some cases poor practice and corner cutting have contributed to lack of reproducibility, and there have been some high profile cases of out and out fraud. It’s a major concern, but what is causing it?

In 2014 I chaired a project on the research culture in Britain for the Nuffield Council on bioethics, which was motivated by concerns about research integrity including over-claiming, rushing prematurely to publication and incorrect use of statistics. The main conclusions were that poor practice is incentivised by hyper-competition with overly narrow rules for winning.

There is an excessive focus on the publication of groundbreaking results in prestigious journals. But science cannot only be groundbreaking, as there is a lot of important digging to do after new discoveries – but there is not enough credit in the system for this work and it may remain unpublished because researchers prioritise their time on the eye-catching papers, hurriedly put together.

The reproducibility crisis is actually a publication bias crisis which is driven by the reward structures in the research system. Various approaches have been suggested to address problems, such as pre-registration of experiments. However, the research landscape is highly diverse and this type of solution is only sensible for some research types. The most widely relevant solution is to change the reward structures. In the UK there is a major opportunity to do this by reforming the Research Excellence Framework (REF). Through the REF, public money is allocated to universities based on the “quality” of the four best research outputs, usually papers, produced by each of their principal investigators over approximately six years and it disproportionately rewards groundbreaking research.

We need reward for a portfolio of research outputs, including not only the headline grabbing results, but also confirmatory work and community data sharing, which are the hallmarks of a truly high quality research endeavour. This would go a long way to shifting the current destructive culture.

Ottoline Leyser, Director of the Sainsbury Laboratory, University of Cambridge; Danny Kingsley, Head, Office of Scholarly Communication, University of Cambridge, University of Cambridge, and Jim Grange, Senior Lecturer in psychology, Keele University

This article was originally published on The Conversation. Read the original article.

The audience of an event at this year’s Cambridge Science Festival found themselves staring into the face of a fellow Cambridge resident – one who had spent the last 700 years buried beneath the venue in which they sat.

The 13th-century man, called Context 958 by researchers, was among some 400 burials for which complete skeletal remains were uncovered when one of the largest medieval hospital graveyards in Britain was discovered underneath the Old Divinity School of St John’s College, and excavated between 2010 and 2012.

The bodies, which mostly date from a period spanning the 13th to 15th centuries, are burials from the Hospital of St John the Evangelist which stood opposite the graveyard until 1511, and from which the College takes its name. The hospital was an Augustinian charitable establishment in Cambridge dedicated to providing care to members of the public.

“Context 958 was probably an inmate of the Hospital of St John, a charitable institution which provided food and a place to live for a dozen or so indigent townspeople – some of whom were probably ill, some of whom were aged or poor and couldn't live alone,” said Professor John Robb, from the University’s Division of Archaeology.

In collaboration with Dr Chris Rynn from the University of Dundee’s Centre for Anatomy and Human Identification, Robb and Cambridge colleagues have reconstructed the man’s face and pieced together the rudiments of his life story by analysing his bones and teeth.

The work is one of the first outputs from the Wellcome Trust-funded project ‘After the plague: health and history in medieval Cambridge’ for which Robb is principal investigator. The project is analysing the St John's burials not just statistically, but also biographically.

“Context 958 was over 40 when he died, and had quite a robust skeleton with a lot of wear and tear from a hard working life. We can't say what job specifically he did, but he was a working class person, perhaps with a specialised trade of some kind,” said Robb.

“One interesting feature is that he had a diet relatively rich in meat or fish, which may suggest that he was in a trade or job which gave him more access to these foods than a poor person might have normally had. He had fallen on hard times, perhaps through illness, limiting his ability to continue working or through not having a family network to take care of him in his poverty.”

There are hints beyond his interment in the hospital’s graveyard that Context 958’s life was one of adversity. His tooth enamel had stopped growing on two occasions during his youth, suggesting he had suffered bouts of sickness or famine early on. Archaeologists also found evidence of a blunt-force trauma on the back of his skull that had healed over prior to his death.  

Click on images below to enlarge:

“He has a few unusual features, notably being buried face down which is a small irregularity for medieval burial. But, we are interested in him and in people like him more for ways in which they are not unusual, as they represent a sector of the medieval population which is quite hard to learn about: ordinary poor people,” said Robb.  

“Most historical records are about well-off people and especially their financial and legal transactions – the less money and property you had, the less likely anybody was to ever write down anything about you. So skeletons like this are really our chance to learn about how the ordinary poor lived.”

The focal point of the ‘After the Plague’ project will be the large sample of urban poor people from the graveyard of the Hospital of St John, which researchers will compare with other medieval collections to build up a picture of the lives, health and day-to-day activities of people living in Cambridge, and urban England as a whole, at this time.

“The After the Plague project is also about humanising people in the past, getting beyond the scientific facts to see them as individuals with life stories and experiences,” said Robb.

“This helps us communicate our work to the public, but it also helps us imagine them ourselves as leading complex lives like we do today. That's why putting all the data together into biographies and giving them faces is so important.”

The Old Divinity School of St John’s College was built in 1877-1879 and was recently refurbished, now housing a 180-seat lecture theatre used for College activities and public events, including last week’s Science Festival lecture given by Robb on the life of Context 958 and the research project.

The School was formerly the burial ground of the Hospital, instituted around 1195 by the townspeople of Cambridge to care for the poor and sick in the community. Originally a small building on a patch of waste ground, the Hospital grew with Church support to be a noted place of hospitality and care for both University scholars and local people.

In a study published today in the journal Molecular Psychiatry, researchers at the University of Cyprus, University of Cambridge, University of California, San Diego, and Stanford University used rats and mice to help map the complex biological cascade caused by the mother’s immune response, which may lead to important consequences.

Maternal infections during pregnancy are a known risk factor for abnormal fetal development. Most strikingly, this has been seen during the recent emergence of Zika virus, which led to babies being born with an abnormally small head and brain (known as ‘microcephaly’). In the case of Zika, the virus has its impact by directly attacking fetal brain tissue. However, for most other infections, such as influenza, the infectious agent typically has a more indirect impact on fetal development.

Large population-based studies have previously shown that a variety of maternal infections during pregnancy are associated with small increases in the risk for psychiatric disorders, including autism spectrum disorders and schizophrenia. Other studies have shown that this effect is due not to the infectious agents themselves, but simply due to triggering a strong immune response in a pregnant mother – a phenomenon known as ‘maternal immune activation’.

“It’s important to underscore that the increase in risk is really small – too small to be meaningfully applied to specific individuals, and is only seen in very large studies when examining many thousands of people,” says Dr Michael Lombardo, lead author of the work from the University of Cyprus and the University of Cambridge. “Nevertheless, the biological cascade triggered by this effect is not well understood, particularly in how it may be similar to known biology behind conditions like autism. This was the motivation behind why we did the study.”

To understand how activating a mother’s immune system may affect her child’s brain development, Dr Lombardo and colleagues examined the activity of genes in the brain after injecting pregnant rats and mice with a substance called lipopolysaccharide. This substance contains no infectious agent and thus does not make the mothers sick, but will elicit a strong immune response in the mother, characterized by an increase in levels of cytokines. These are small immune signalling molecules that can have important effects on brain cells and the connections between these cells (known as ‘synapses’ in the fetus’s brain.

The scientists found that maternal immune activation alters the activity of multiple genes and pathways in the fetus’s brain. Importantly, many of these genes are known to be important in the development of autism and to key brain developmental processes that occur before birth. They believe that these effects may help to explain why maternal immune activation carries a small increased risk for later atypical neurodevelopment.

“The more we understand about how brain development is disrupted by these effects, the higher the chance of finding amenable targets for potential therapeutic intervention or for informing how to prevent such risk from occurring in the first place,” says Dr Tiziano Pramparo, senior author on the work from the University of California, San Diego.

While the effects caused by maternal immune activation are transient, the researchers argue that they may be very potent during fetal development and may cause different characteristics in the individual depending on when it occurs during pregnancy. The work underscores the importance of the idea that genes and the environment interact and that their interaction may have important roles in better understanding how risk for neurodevelopmental disorders manifests.

The research was funded in part by the University of California San Diego Altman Clinical and Translational Research Institute, the National Institutes of Health, the Simons Foundation Autism Research Initiative and the Child Health Research Institute at Stanford University.

Reference
Lombardo, MV et al. Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder. Molecular Psychiatry; 21 March 2017; DOI: 10.1038/mp.2017.15

Acute famine in the Horn of Africa, an impending food crisis in Yemen and ongoing civil war in Syria are among the main causes of today’s global refugee crisis. Currently there are more than 65.3m people displaced across the globe and over 5,000 refugees died or went missing in the Mediterranean in 2016 on their way to Europe, making it the deadliest year on record.

While humanitarian organisations struggle to cope, it seems to be standard and accepted practice for the media to bash them for their work. Criticism is varied and extensive, but what the media seems to agree on is that humanitarian NGOs, charities and UN organisations are all inefficient and expensive. They are accused of disappointing efforts to come up with better aid programmes and ultimately failing to provide any results for their work.

Dangerous work and constant rotations

But it is a risky job to deliver aid in crises environments. In 2015, the Guardian reported that it has rarely ever been more dangerous to be an aid worker. And the statistics speak for themselves. In 2015, 148 attacks on aid workers were recorded with 109 people killed, 110 injured and 68 kidnapped.

In order to protect their staff, many organisations operate a strict rotation policy, which means that staff members have to leave an acute emergency operation after every three to six months or every second year. Such policies ensure that people can alternate between more and less dangerous posts, allowing them to rest and recover. OCHA, the UN Office for the Coordination of Humanitarian Affairs, for instance, has an emergency response roster with staff deployed to crises outbreaks usually for six to eight weeks.

Other organisations such as UNHCR, the UN Refugee Agency, works with roving positions. To respond immediately to crises and subsequent displacement, roving staff can be deployed to any emergency operation within 72 hours to assist local offices. A roving staff member whom I met during my research told me she sleeps next to her suitcase packed and ready, always on the move.

Little long-term memory

Such rotation policies are necessary, but they obviously present a challenge to the efficiency and effectiveness of humanitarian work. Emergency relief needs to be extremely fast paced, setting up camps, providing food, water and health services to thousands of displaced people in a matter of a few days.

In such context, staff should ideally rely on lessons learned and a good institutional memory of the local operation, but constant turnover makes information sharing difficult and the development of a long-term institutional memory is hard to achieve. And while new staff members in other organisations learn from colleagues who have been doing the same job for a few years, frequent staff rotations between Rwanda, Syria or Yemen make personal handovers almost impossible. So humanitarian workers often find themselves thrown in at the deep end.

Passing on knowledge

In order to deal with these challenges, humanitarian organisations need to be creative. The UN Refugee Agency, for instance, is currently piloting a global platform on good practices for staff assisting urban refugees, highlighting ways of addressing sexual violence or employment assistance that proved successful in other countries. The aim is to disseminate lessons learnt and best practices online. Humanitarian workers can proactively search for examples that might work in their own contexts by searching and filtering the database, instead of relying on personal handovers.

Another charity, Engineers without Borders, often working in the aftermath of a first emergency response, publicly celebrates failures through its annual Failure Report. Its purpose is to give others the chance to learn from failures faster. Meanwhile, Save the Children is investing heavily in online learning courses. Staff members are trained on general operational systems or security procedures online before being sent to an emergency. Other training courses are designed to foster a better understanding of the organisation’s values and ways of doing things in order to develop a more global institutional memory.

Humanitarian organisations can easily be dismissed as inefficient and not effective, but they are operating in a challenging environment, constantly on the move to tackle global emergency and refugee crises.

Corinna Frey, PhD Candidate, Cambridge Judge Business School

This article was originally published on The Conversation. Read the original article.

Capital cities across Asia spent the last month rolling out the red carpet for a rarely seen visitor: Saudi Arabia’s ageing King Salman, accompanied by a hundreds-strong diplomatic entourage including senior princes, businessmen and ministers. Taking in Malaysia, Indonesia, Brunei, Japan, China and the Maldives, the king spent March leading a concerted effort to strengthen Saudi Arabia’s commercial links with Asia’s fast-growing economies.

The House of Saud doesn’t usually go in for long state visits, and no Saudi king has visited Indonesia for half a century. So the fact that the Saudi king committed to a full month away in this part of the world speaks volumes about his government’s mood after a series of strategic miscalculations.

Saudi rulers have always worried about the prospect of diplomatic isolation, and stronger relations with Asia are in some ways part of the usual agenda. But they’ve now become a lifeline with which to save the kingdom from its bad bets in the Middle East. Saudi Arabia’s recent efforts to settle its incessant rivalry with Iran have not paid off, and after flooding the market with cheap oil and engineering a fall in the oil price to Iran’s detriment, the Saudis are now themselves faced with a festering budget deficit, forcing them to slash spending on infrastructure and reduce civil servant perks to get finances under control.

Elsewhere, the devastating war in Yemen is exposing Saudi Arabia to both military pressure and severe international condemnation for the humanitarian catastrophe the campaign has caused. Recent decisions taken in Organisation of the Petroleum Exporting Countries (OPEC), meanwhile, forced Saudi Arabia to swallow a big hit on its oil production, suggesting that it can no longer afford an aggressive anti-Iran policy in Yemen without new allies and partners to shore it up.

In these squeezed times, South-East Asia’s growing economies have much to offer to the Saudis.

Finance diplomacy

Historically, the pilgrimage from Asia to Islam’s holy cities of Mecca and Medina has been an important revenue source for the kingdom’s volatile budget, but King Salman’s failing regional fortunes and financial problems have placed renewed impetus on moving the kingdom away from its traditional dependence on oil.

King Salman has found a receptive audience in the Asian capitals. Malaysia is already making a strong turn to the Saudi fold; in early 2016, it joined military exercises in northern Saudi territory involving around 150,000 soldiers, 2,540 warplanes, 20,000 tanks, and 460 helicopters. The exercise has been fuelling rumours that Malaysia might be swayed to join Saudi Arabia’s military campaign in Yemen, which already benefits from the support of several other Muslim-majority states.

This is not a strange expectation. Personal relations between Prime Minister Najib Razak and the Saudi royal family are reported to be strong, and the Saudis played a key role in helping to save Razak’s political career from a major scandal. By publicly confirming Razak’s claim that an unaccounted US$681m in his bank accounts was a donation from the Saudi royal family, the Saudis helped to counter accusations that he had in fact siphoned the money from heavily indebted state investment fund 1MDB.

Economic opportunities abound. Upon arrival in Kuala Lumpur in late February, national oil and gas company Saudi Aramco signed a US$7 billion agreement with Malaysian oil company Petronas. The deal will pump Saudi investment into a Malaysian petrochemical project valued at US$27 billion, making Aramco the single largest investor in Malaysia. The deal is also expected to improve Malaysia’s chances to compete in oil refining and energy storage, an industry currently monopolised by Singapore in South-East Asia.

Indonesia, too, hopes to attract billions of dollars in Saudi investment. The two countries have signed more than ten memorandums of understanding, building on cultural and religious projects, promoting educational exchange and intensifying trade. Together with Indonesia’s Pertamina, Saudi Aramco has committed to expand Indonesia’s biggest refinery in Java. The total value of the agreements stretches into the billions.

The Saudis are highly skilled in this sort of fast-paced “finance diplomacy”. Like estranged family members coming home with presents, they bring in their wake large sums of money for development finance and the promise of several billions of dollars of investment opportunities for the relations they hope to cultivate.

And beyond pure financial interests, it’s worth remembering that these joint investment ventures create the sort of long-term partnerships that give external partners a stake in Saudi Arabia’s own security and development. These sorts of financial patronage projects extend far beyond trade and commerce – since the 1970s, Saudi oil money has persistently found its way to foreign schools, charities, mosques and nonprofits to promote a religious ideology which is at odds with the traditional brand of moderate Islam practised in South-East Asia. Donations by dozens of Saudi waqfs (Islamic charitable endowments) all fuel the elite’s drive to project itself as the leader of Sunni Muslims the world over.

Investment with the heft the Saudis offer is too tempting to pass up, but King Salman’s visit will only help export his country’s hardline doctrine to places where that could do without it. Both Malaysia and Indonesia urgently need to ease tensions between restive religious communities, but Saudi Arabia aims to open more Islamic schools across South-East Asia, increasing not only literacy in the Arabic language but also Saudi religious teaching and influence. That could be a heavy price tag indeed.

Babak Mohammadzadeh, PhD Candidate in Politics and International Studies, University of Cambridge

This article was originally published on The Conversation. Read the original article.

For 130 years palaeontologists have been working with a classification system in which dinosaur species have been placed in to two distinct categories: Ornithischia and Saurischia. But now, after careful analysis of dozens of fossil skeletons and tens of thousands of anatomical characters, the researchers have concluded that these long-accepted familial groupings may, in fact, be wrong and that the traditional names need to be completely altered.

The classification of dinosaurs dates back to Victorian times. Dinosaurs were first recognised as a unique group of fossil reptiles in 1842 as a result of the work of the anatomist, Professor Richard Owen (who later went on to found the Natural History Museum in London). Over subsequent decades, various species were named as more and more fossils were found and identified. During the latter half of the 19th century it was realised that dinosaurs were anatomically diverse and attempts were made to classify them into groups that shared particular features.

It was Harry Govier Seeley, a palaeontologist trained in Cambridge under the renowned geologist Adam Sedgwick, who determined that dinosaurs fell quite neatly into two distinct groupings, or clades; Saurischia or Ornithischia. This classification was based on the arrangement of the creatures’ hip bones and in particular whether they displayed a lizard-like pattern (Saurischia) or a bird-like one (Ornithischia).

As more dinosaurs were described it became clear that they belonged to three distinct lineages; Ornithischia, Sauropodomorpha and Theropoda. In 1887 Seeley placed the sauropodomorphs (which included the huge ‘classic’ dinosaurs such as Diplodocus and Brontosaurus) together with the  theropods (which included T. rex), in the Saurischia. The ornithischians and saurischians were at first thought to be unrelated, each having a different set of ancestors, but later study showed that they all evolved from a single common ancestor.   

This new analysis of dinosaurs and their near relatives, published today in the journal Nature, concludes that the ornithischians need to be grouped with the theropods, to the exclusion of the sauropodomorphs. It has long been known that birds (with their obviously ‘bird-like’ hips) evolved from theropod dinosaurs (with their lizard-like hips). However, the re-grouping of dinosaurs proposed in this study shows that both ornithischians AND theropods had the potential to evolve a bird-like hip arrangement- they just did so at different times in their history.

Lead author, Matthew Baron, says:

“When we started our analysis, we puzzled as to why some ancient ornithischians appeared anatomically similar to theropods. Our fresh study suggested that these two groups were indeed part of the same clade. This conclusion came as quite a shock since it ran counter to everything we’d learned.”

“The carnivorous theropods were more closely related to the herbivorous ornithischians and, what’s more, some animals, such as Diplodocus, would fall outside the traditional grouping that we called dinosaurs. This meant we would have to change the definition of the ‘dinosaur’ to make sure that, in the future, Diplodocus and its near relatives could still be classed as dinosaurs.”

The revised grouping of Ornithischia and Theropoda has been named the Ornithoscelida which revives a name originally coined by the evolutionary biologist, Thomas Henry Huxley in 1870. 

Co-author, Dr David Norman, of the University of Cambridge, says:

“The repercussions of this research are both surprising and profound. The bird-hipped dinosaurs, so often considered paradoxically named because they appeared to have nothing to do with bird origins, are now firmly attached to the ancestry of living birds.”

For 130 years palaeontologists have considered the phylogeny of the dinosaurs in a certain way. Our research indicates they need to look again at the creatures’ evolutionary history. This is simply science in action. You draw conclusions from one body of evidence and then new data or theories present themselves and you have to suddenly reconsider and adapt your thinking. All the major textbooks covering the topic of the evolution of the vertebrates will need to be re-written if our suggestion survives academic scrutiny.”

While analysing the dinosaur family trees the team arrived at another unexpected conclusion. For many years, it was thought that dinosaurs originated in the southern hemisphere on the ancient continent known as Gondwana. The oldest dinosaur fossils have been recovered from South America suggesting the earliest dinosaurs originated there. But as a result of a re-examination of key taxa it’s now thought they could just as easily have originated on the northern landmass known as Laurasia, though it must be remembered that the continents were much closer together at this time. 

Co-author, Prof Paul Barrett, of the Natural History Museum, says:

"This study radically redraws the dinosaur family tree, providing a new framework for unravelling the evolution of their key features, biology and distribution through time. If we're correct, it explains away many prior inconsistencies in our knowledge of dinosaur anatomy and relationships and it also highlights several new questions relating to the pace and geographical setting of dinosaur origins".

The research was funded through a Natural Environment Research Council (NERC) CASE studentship.

Matthew Baron et al: 'A new hypothesis of dinosaur relationships and early dinosaur evolution'Nature, 23 March 2017 

10.1038/nature21700

A short video guide has been prepared by the Natural History Museum to accompany this paper.

Marauding hordes of barbarian Huns, under their ferocious leader Attila, are often credited with triggering the fall of one of history’s greatest empires: Rome. 

Historians believe Hunnic incursions into Roman provinces bordering the Danube during the 5th century AD opened the floodgates for nomadic tribes to encroach on the empire. This caused a destabilisation that contributed to collapse of Roman power in the West.

According to Roman accounts, the Huns brought only terror and destruction. However, research from the University of Cambridge on gravesite remains in the Roman frontier region of Pannonia (now Hungary) has revealed for the first time how ordinary people may have dealt with the arrival of the Huns.

Biochemical analyses of teeth and bone to test for diet and mobility suggest that, over the course of a lifetime, some farmers on the edge of empire left their homesteads to become Hun-like roaming herdsmen, and consequently, perhaps, took up arms with the tribes.

Other remains from the same gravesites show a dietary shift indicating some Hun discovered a settled way of life and the joys of agriculture – leaving their wanderlust, and possibly their bloodlust, behind.

Lead researcher Dr Susanne Hakenbeck, from Cambridge’s Department of Archaeology, says the Huns may have brought ways of life that appealed to some farmers in the area, as well learning from and settling among the locals. She says this could be evidence of the steady infiltration that shook an empire.  

“We know from contemporary accounts that this was a time when treaties between tribes and Romans were forged and fractured, loyalties sworn and broken. The lifestyle shifts we see in the skeletons may reflect that turmoil,” says Hakenbeck.

“However, while written accounts of the last century of the Roman Empire focus on convulsions of violence, our new data appear to show some degree of cooperation and coexistence of people living in the frontier zone. Far from being a clash of cultures, alternating between lifestyles may have been an insurance policy in unstable political times.”

For the study, published today in the journal PLOS ONE, Hakenbeck and colleagues tested skeletal remains at five 5th-century sites around Pannonia, including one in a former civic centre as well as rural homesteads.

The team analysed the isotope ratios of carbon, nitrogen, strontium and oxygen in bones and teeth. They compared this data to sites in central Germany, where typical farmers of the time lived, and locations in Siberia and Mongolia, home to nomadic herders up to the Mongol period and beyond.     

The results allowed researchers to distinguish between settled agricultural populations and nomadic animal herders in the former Roman border area through isotopic traces of diet and mobility in the skeletons. 

All the Pannonian gravesites not only held examples of both lifestyles, but also many individuals that shifted between lifestyles in both directions over the course of a lifetime. “The exchange of subsistence strategies is evidence for a way of life we don’t see anywhere else in Europe at this time,” says Hakenbeck.

She says there are no clear lifestyle patterns based on sex or accompanying grave goods, or even ‘skull modification’ – the binding of the head as a baby to create a pointed skull – commonly associated with the Hun.

“Nomadic animal herding and skull modification may be practices imported by Hun tribes into the bounds of empire and adopted by some of the agriculturalist inhabitants.”

The diet of farmers was relatively boring, says Hakenbeck, consisting primarily of plants such as wheat, vegetables and pulses, with a modicum of meat and almost no fish.

The herders’ diet on the other hand was high in animal protein and augmented with fish. They also ate large quantities of millet, which has a distinctive carbon isotope ratio that can be identified in human bones. Millet is a hardy plant that was hugely popular with nomadic populations of central Asia because it grows in a few short weeks.

Roman sources of the time were dismissive of this lifestyle. Ammianus Marcellinus, a Roman official, wrote of the Hun that they “care nothing for using the ploughshare, but they live upon flesh and an abundance of milk.” 

“While Roman authors considered them incomprehensibly uncivilised and barely human, it seems many of citizens at the edge of Rome’s empire were drawn to the Hun lifestyle, just as some nomads took to a more settled way of life,” says Hakenbeck.

However, there is one account that hints at the appeal of the Hun, that of Roman politician Priscus. While on a diplomatic mission to the court of Attila, he describes encountering a former merchant who had abandoned life in the Empire for that of the Hun enemy as, after war, they “live in inactivity, enjoying what they have got, and not at all, or very little, harassed.” 

The finding that moderate drinking is not universally associated with a lower risk of all cardiovascular conditions suggests a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary, say the researchers.

Moderate drinking is thought to be associated with a lower risk of developing cardiovascular disease compared with abstinence or heavy drinking.

In the UK, moderate drinking is defined as no more than 14 units of alcohol a week, the equivalent of 7 pints of ordinary strength beer or just over one and a half bottles of ordinary strength wine.

There is, however, a growing scepticism around this observation, with some experts pointing out several shortcomings in the evidence, for example grouping non-drinkers with former drinkers, who may have stopped drinking due to poor health.

Researchers at the University of Cambridge and University College London set out to investigate the association between alcohol consumption and 12 cardiovascular diseases by analysing electronic health records for 1.93 million healthy UK adults as part of the CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records) data resource.

All participants were free from cardiovascular disease at the start of the study, and non-drinkers were separated from former and occasional drinkers to provide additional clarity in this debate.

The researchers looked at the effect of different levels of drinking on the risk of ‘first presenting’ to a doctor with a number of cardiovascular diseases; for example, did moderate drinking make it more or less likely that an individual’s first diagnosis of cardiovascular disease was a heart attack.

After several influential factors were accounted for, moderate drinking was associated with a lower risk of several, but not all, cardiovascular conditions, including angina, heart failure and ischaemic stroke (the most common type of stroke, when a blood clot blocks the flow of blood and oxygen to the brain), compared with abstaining from alcohol.

“This doesn’t mean that it is advisable for individuals to take up drinking as a means of lowering their cardiovascular risk,” says Dr Steven Bell from the Department of Public Health and Primary Care at the University of Cambridge. “Alcohol consumption is associated with other diseases, such as liver disease and certain types of cancer. There are other, safer and more effective ways, such as being more physically active, maintaining a healthy diet and stopping smoking.

“Ultimately an individual’s decision to drink, and at what level, should not be considered in isolation of other health behaviours or risk factors and instead be motivated by their own personal circumstances.”

Heavy drinking (exceeding recommended limits) conferred an increased risk of a range of cardiovascular diseases, including heart failure, cardiac arrest (when the heart malfunctions and stops beating suddenly) and ischaemic stroke compared with moderate drinking. However, it carried a lower risk of heart attack (when blood flow to the heart is blocked) and angina.

Again, the authors explain that this does not mean that heavy drinkers will not go on to experience a heart attack in the future, just this was less likely to be their first diagnosis compared with moderate drinkers.

This is an observational study, so no firm conclusions can be drawn about cause and effect. Added to which, the authors point to some study limitations that could have introduced bias.

Nevertheless, they say it is the first time this association has been investigated on such a large scale and their findings have implications for patient counselling, public health communication, and disease prediction tools.

In a linked editorial, researchers at Harvard Medical School and Johns Hopkins School of Public Health in the US say this study “sets the stage for ever larger and more sophisticated studies that will attempt to harness the flood of big data into a stream of useful, reliable, and unbiased findings that can inform public health, clinical care, and the direction of future research”.

Reference
Bell, S et al. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ; 23 Mar 2017; DOI: 10.1136/bmj.j909

Adapted from a press release from The BMJ.

R. Derek Finlay is donating £5 million to fund the completion of the Chemistry of Health building, in the Department of Chemistry, and to support new research into neurodegenerative diseases.

The building, which is due to open in 2018, will house the Centre for Misfolding Diseases, which is driving ground-breaking research into how protein molecules ‘misfold’, leading to diseases such as Alzheimer’s, Parkinson’s and type 2 diabetes.

Finlay has had personal experience of the impact such devastating disorders can have. He lost his wife, Una Finlay, in 2016 to Alzheimer’s disease. Today, he unveiled a plaque dedicating the laboratories that will be occupied by the Centre for Misfolding Diseases to his late wife. This plaque will be placed within the Chemistry of Health building when it opens in 2018.

He said, “It is my hope that the new Chemistry of Health Building will enable breakthroughs to be made in our understanding of neurodegenerative diseases, bringing us closer to the development of new treatments. My gift to support Cambridge’s pioneering work in this area is in memory of my dear late wife, Una, herself a sufferer of Alzheimer’s.”

The Centre’s research, which is directed by Christopher Dobson, Professor of Chemical and Structural Biology, is taking forward understanding of misfolding proteins in humans and looking at ways to accelerate the development of new diagnostics and therapeutics.

Professor Dobson said: “We are enormously grateful for this generous benefaction from Derek, and honoured that our laboratories within the building will be named after his late wife Una. Disorders such as Alzheimer’s and Parkinson’s disease are becoming frighteningly common in the modern world. The Chemistry of Health building will enable us to make a giant step forward in translating recent breakthroughs made in Cambridge into future treatments to combat these rapidly proliferating and truly devastating conditions.”

Finlay is a long-standing donor to Collegiate Cambridge, supporting a number of initiatives in his College, Emmanuel. The College Museum is endowed and named in honour of his brother, Douglas Finlay. He also attended the College (1941) and died in a flying accident in 1948, having served in RAF Bomber Command 1941-45 including nearly two years as a Prisoner of War in Stalag Luft III in Sagan, Germany.

Following Finlay’s most recent gift to Cambridge, he has been made a Companion of the Guild of Cambridge Benefactors at a ceremony last night (22 March) held at the University of Cambridge.

The Guild of Cambridge Benefactors was established in 1998 to recognise the generosity of major benefactors to the University of Cambridge and its Colleges. The annual ceremony of admission to the Guild is an opportunity for the University to acknowledge its closest friends and supporters, and celebrate their central role in the success of the University. This year 15 Companions were admitted to the Guild.

Cambridge launched its £2 billion Dear World… Yours, Cambridge philanthropic campaign for the University and Colleges in October 2015.  It has just celebrated its most successful fundraising year ever, raising more than £210 million including Finlay’s gift.

Human pluripotent stem cells are ‘master cells’ that have the ability to develop into almost any type of tissue, including brain cells. They hold huge potential for studying human development and the impact of diseases, including cancer, Alzheimer’s, multiple sclerosis, and heart disease.

In a human, it takes nine to twelve months for a single brain cell to develop fully. It can take between three and 20 weeks using current methods to create human brain cells, including grey matter (neurons) and white matter (oligodendrocytes) from an induced pluripotent stem cell – that is, a stem cell generated by reprogramming a skin cell to its ‘master’ stage. However, these methods are complex and time-consuming, often producing a mixed population of cells.

The new platform technology, OPTi-OX, optimises the way of switching on genes in human stem cells. Scientists applied OPTi-OX to the production of millions of nearly identical cells in a matter of days. In addition to the neurons, oligodendrocytes, and muscle cells the scientists created in the study, OPTi-OX holds the possibility of generating any cell type at unprecedented purities, in this short timeframe.

To produce the neurons, oligodendrocytes, and muscle cells, the team altered the DNA in the stem cells. By switching on carefully selected genes, they reprogrammed the stem cells and created a large and nearly pure population of identical cells. The ability to produce as many cells as desired combined with the speed of the development gives an advantage over other methods. The new method opens the door to drug discovery, and potentially therapeutic applications in which large amounts of cells are needed.

Study author Professor Ludovic Vallier from the Wellcome Trust-Medical Research Centre Stem Cell Institute at the University of Cambridge says: “What is really exciting is we only needed to change a few ingredients – transcription factors – to produce the exact cells we wanted in less than a week. We over-expressed factors that make stem cells directly convert into the desired cells, thereby bypassing development and shortening the process to just a few days.”

OPTi-OX has applications in various projects, including the possibility to generate new cell types which may be uncovered by the Human Cell Atlas. The ability to produce human cells so quickly means the new method will facilitate more research.

Joint first author, Daniel Ortmann from the University of Cambridge, adds: “When we receive a wealth of new information on the discovery of new cells from large scale projects, like the Human Cell Atlas, it means we’ll be able to apply this method to produce any cell type in the body, but in a dish.”

Dr Mark Kotter, lead author and clinician, also from Cambridge, says: “Neurons produced in this study are already being used to understand brain development and function. This method opens the doors to producing all sorts of hard-to-access cells and tissues so we can better our understanding of diseases and the response of these tissues to newly developed therapeutics.”

The research was supported by Wellcome, the Medical Research Council, the German Research Foundation, the British Heart Foundation, The National Institute for Health Research UK and the Qatar Foundation.

Reference
Matthias Pawlowski et al. Inducible and deterministic forward programming of human pluripotent stem cells. Stem Cell Reports; 23 Mar 2017; DOI: 10.1016/j.stemcr.2017.02.016

Adapted from a press release by the Wellcome Trust Sanger Institute.

Published today in the journal Nature Genetics, the findings are the result of work by the OncoArray Consortium, a huge endeavour led by scientists in the UK, the USA and Australia. This particular study involved 418 researchers from almost 300 different departments worldwide.

According to Cancer Research UK, there were 7,378 new cases of ovarian cancer in the UK in 2014. Around nine out of ten of these cases was epithelial ovarian cancer. The peak rate of cases is among women aged 75-79 years old.

“We know that a woman’s genetic make-up accounts for about one third of her risk of developing ovarian cancer. This is the inherited component of disease risk,” explains Professor Paul Pharoah from the University of Cambridge, UK, one of the joint leads. “We’re less certain of environmental factors that increase our risk, but we do know that several factors reduce the risk of ovarian cancer, including taking the oral contraceptive pill, having your tubes tied and having children.”

Inherited faults in genes such as BRCA1 and BRCA2 account for about 40 per cent of the inherited component.  These faults are rare in the population (carried by about one in 300 people) and are associated with high lifetime risks of ovarian cancer – about 50 per cent for BRCA1 and 16 per cent for BRCA2 on average – as well as a high risk of breast cancer. Variants that are common in the population (carried by more than one in 100 people) are believed to account for most of the rest of the inherited component of risk.

Before the OncoArray Consortium, researchers had identified 27 common variants across the genome associated with ovarian cancer risk.  However, some of these are associated only with rare subtypes of ovarian cancer.  The magnitude of the associated risk however is modest: together, the variants account for only about 4 per cent of the inherited component of disease.

The OncoArray Consortium studied the genomes of over 25,000 people with epithelial ovarian cancer and compared them to almost 41,000 healthy controls. They then analysed results from a further 31,000 BRCA1 and BRCA2 mutation carriers, which included almost 4,000 epithelial ovarian cancer patients. This enabled them to identify a further 12 variants associated with risk and confirm the association of 18 of the previously published variants; some of the other variants failed to replicate.

In total, there are now known to be 30 risk variants, accounting for 6.5 per cent of the inherited component of risk.

“Ovarian cancer is clearly a very complex disease – even the 30 risk variants that we now know increase risk of developing the disease account for just a small fraction of the inherited component,” says Dr Catherine Phelan from the Moffitt Cancer Center, Tampa, USA. “We believe that there will likely be many more genetic variants involved, each with extremely small effects.  Most of these are likely to be common, but some will be rare.”

The researchers point out that while the common view is of our genes influencing disease risk, in fact most of the variants discovered to date do not fall in our genes, but rather in ‘non-coding’ regions of the human genome, so named because, unlike our genes, they do not provide the code to make proteins. Instead, these regions are often involved in regulating the activity of our genes.

Because the variants are common, some women will carry multiple risk variants.  However, even in combination these variants do not have a large effect on risk, say the researchers. Women carrying the greatest number of these risk variants will still have a lifetime risk of ovarian cancer of just 2.8 per cent.  To put this into context, family cancer clinics commonly offer surgery to remove the ovaries – and hence prevent the possibility of disease – to women with a lifetime risk of 10 per cent or more.  

However, these variants also affect the risk of ovarian cancer in women who carry a fault in the BRCA1 or BRCA2 genes and this might be sufficient to affect the decision of a carrier about when or if to have preventive surgery.  

“In some ways, the hard work starts now,” says Dr Simon Gayther from Cedars-Sinai Medical Center, Los Angeles, USA. “We really have little idea of the functional effect these variants have at the molecular or cellular level and so there are few clues as to how they might affect risk. If we can understand how they work, we will be in a better position to treat – and possibly prevent – ovarian cancer.”

The research was carried out by the Ovarian Cancer Association Consortium and the Consortium of Investigators of Modifiers of BRCA1/2, two consortia that are part of the larger OncoArray Consortium. The consortia used a customised Illumina genotyping array, which allowed them to analyse around 533,000 variants and has been used to genotype over 500,000 samples, including the samples in this study of ovarian cancer

Reference
Phelan, CM et al. Identification of twelve novel susceptibility loci for different histotypes of epithelial 1 ovarian cancer. Nature Genetics; 27 Mar 2017; DOI: 10.1038/ng.3826

This is the charity’s single largest grant to date and will create an institute that is the first of its kind in Europe.

Led by Mary Dixon-Woods, RAND Professor of Health Services Research and Wellcome Trust Investigator at the University of Cambridge, the institute will work closely with a wide range of partners across the UK including RAND Europe and Homerton College, Cambridge. Seeking to strengthen the evidence-base for how to improve health care, it will produce practical, high quality learning about how to improve patient care and will grow capacity in research skills in the NHS, academia and beyond.

The Health Foundation says it is making this significant investment because it recognises the huge potential for research to shed light on how sustainable and replicable improvements to the quality of patient care can be made in the NHS more quickly.

Dr Jennifer Dixon, chief executive of the Health Foundation, says: “Faster learning and discovery is vital to achieving higher quality health care for patients at a sustainable cost. That is why the Health Foundation is making its biggest single grant to date to help build the field of improvement research.

“The University of Cambridge and their partners have set out a compelling vision for this ground-breaking improvement research institute – the first of its kind in Europe. This is a significant and exciting step in developing evidence on a massive scale across the NHS about what works to improve patient care. Critically, the institute’s work will include understanding not only which interventions work, but also in which contexts and why.”

Professor Dixon-Woods adds: “The NHS, like health systems around the world, is faced with pressing challenges of quality and safety. Yet the science of how to make improvements has remained under-developed. This funding is a tremendous opportunity to produce new knowledge about how to improve care, experience and outcomes for patients. Together with our partners, the University of Cambridge is hugely excited at the chance to work with NHS staff, patients and carers to identify, design and test improvements.”

The institute will formally launch within the next year and will be based at the Cambridge Biomedical Campus, alongside Cambridge University Hospitals NHS Foundation Trust and world-leading research institutes.

For more information, please visit the Health Foundation's website.

Adapted from a press release from the Health Foundation.

Schoolchildren who receive words of encouragement from a teacher are significantly more likely to continue their education beyond the age of 16 than those who do not, a new study suggests.

The influence of teacher encouragement appears to be much greater on students whose own parents never progressed past compulsory education – an important indicator of a less advantaged background.

For students from these backgrounds, encouragement increased entry into post-16 education from just over half to around two-thirds.  

The research also found that encouragement from a teacher has the greatest influence on those students most likely to be on the margin for university attendance.  

The University of Cambridge study used ‘big data’ techniques to look at the long-term impact of student-teacher rapport, and is the first to analyse the role it plays in university access. 

The findings, published in the journal Research in Higher Education, show that further education and social mobility policymaking might benefit from increased focus on the “relational aspects” of interactions between teachers and students. 

“Teachers are often relegated to course deliverers and classroom managers in the policy discussions around further education. However, it’s clear that teachers have more forms of influencing inequality than is currently appreciated,” said study author Dr Ben Alcott from Cambridge’s Faculty of Education.   

“When people speak of a positive school experience, they frequently cite a personal relationship with a teacher, and the encouragement they were given. Our research helps quantify that impact and show its significance, particularly for addressing social mobility.

“The importance of that teacher-student connection can get lost in the midst of exam statistics or heat of political debate.”

Some 4,300 adolescents in England were tracked from the age of thirteen onwards, completing a detailed questionnaire every year for the next seven years. During their last year of compulsory education, the students were asked whether a teacher had encouraged them to stay on in full-time education. 

Dr Alcott used mathematical modelling to “match” and compare students with similar attainment, experience and life histories – helping control for the effects these differences had. This makes it possible for the influence of teacher encouragement alone to be measured.

“This approach brings us plausibly close to reading the long-term effect of encouragement from teachers with the data we currently have available,” Alcott said. 

He found that, on average across all backgrounds and abilities, rates of entry into post-16 education were eight percentage points higher in students that reported receiving encouragement (74%) over those that said they did not (66%).

Based on previous examination scores (the UK’s SATs), teacher encouragement made the most difference for students with average academic achievement – those often on the verge of going either way when it comes to further education.

For Year 11 (or 10th grade) students in the middle third of results rankings, encouragement was linked to a 10 percentage-point increase in the likelihood of university entry, yet had no observable impact on students in the upper and lower thirds.    

The effect of teacher encouragement on students varied considerably depending on background – with the greatest difference seen for students with lower levels of parental education.

For students with parents who lacked any formal qualification, post-16 education enrolment increased 12 percentage points amongst those who received teacher encouragement (64%) compared with those who didn’t (52%).

This effect appeared to last into higher education, with that initial encouragement increasing the likelihood of university entry by 10 percentage points – one-fifth higher than students from similar backgrounds who did not report being encouraged.    

Students whose parents had some qualifications, but none past compulsory education, saw encouragement from teachers boost post-16 education by 13 percentage points (67% compared to 54%) and university entry by seven percentage points.

For those with parents who held university degrees, however, teacher encouragement mattered much less: increasing continued education by just six percentage points and making no difference at all to university attendance.

However, Alcott found that students from more advantaged backgrounds were likelier to report being encouraged by a teacher to stay in education.

For example, 22% of students receiving encouragement had a parent with a university degree, compared to 15% of those who did not. Similarly, students who do not report encouragement are a third more likely to have an unemployed parent (12% versus 9%).

Alcott, who formerly taught in a London academy school himself, says: “These results suggest that teachers themselves and the relationships they develop with students are real engines for social mobility.

“Many teachers take the initiative to encourage students in the hope they will progress in education long after they have left the classroom. It’s important that teachers know the effect their efforts have, and the children likely to benefit most.” 

When David Adam was just 18, a teasing comment from a university friend triggered a series of thoughts that he had contracted HIV and would die of AIDS. This was around the time of peak hysteria about this new disease, but even so, his thoughts represented more than the worries of a naïve, newly-sexually active young man: the fear was unshakeable and the thoughts consumed him, dominating his life.

For a long time, David remained silent about his obsession, afraid to tell anyone what he was going through. It was only a couple of decades later, when the thoughts began to affect his relationship with his young daughter, to whom he was sure he would transmit his ‘infection’, that he sought help. He was subsequently diagnosed with obsessive compulsive disorder (OCD).

OCD is sometimes viewed as a personality quirk – “I’m a little bit OCD,” people will say as they carefully arrange the books on their shelf. The truth is far more devastating. People living with OCD will scrub their hands compulsively, often with bleach, till they are bleeding. Others will check that they have locked the back door thirty, forty times – otherwise, they are sure a family member will come to harm - making going out almost impossible.

David, a journalist and science writer, has written and spoken extensively about his condition. He considers himself fortunate: his condition is under control, thanks to a combination of ‘talking therapies’ and medication. Others are not so fortunate: despite intensive therapy and medication, they are still unable to hold down a job or a relationship, so dominant are their OCD behaviours.

Now, in a series of short films for the University of Cambridge, David has visited leading researchers who study OCD and asks what we know about the underlying biology that leads to the condition: just what is going on in the brain?

In the films, Professor Trevor Robbins, Head of Psychology at Cambridge, introduces David to scientists who use a combination of studies to explore the inner workings of the brain. These include studies involving rats and marmosets (small monkeys), as well as people.

One of the studies is a so-called ‘reversal learning’ test. In this test, the marmoset learns that pressing one button gives it a juice reward, while it gets no reward if it presses a second button. But then, unexpectedly, the buttons swap: how good is the marmoset at changing its thinking to adjust to this new information? A common trait in people with OCD is a tendency to have rigid, obsessive thinking that dominates their behaviour.

By manipulating localised regions of the animals’ brains, either permanently or via temporary drug infusions, scientists are able to understand better the exact pathways within the brain that malfunction in OCD and cause this rigid behaviour. As Professor Robbins explains, this would not be possible in human studies. But this knowledge will help underpin the development of new, more effective treatments – and this is crucial, as around 60% of patients with OCD do not respond to existing treatments.

The films have been produced as part of the University of Cambridge’s commitment to openness on animal research. In 2014, the University announced that it had signed the Concordat on Openness on Animal Research. The following year, it launched its first film on the subject, Fighting Cancer: Animal research at Cambridge.

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On 5 May 1801 the novelist Jane Austen sat down in an upper room of a terraced house in Bath to write to her sister Cassandra. She had that day arrived in the popular spa town, following her father’s decision to leave the family home at Steventon in Hampshire.This decision had been distressing to Austen, who was 25 years old when she wrote this letter.

Austen’s letter is rich in detail about Bath, some damp accommodation, “the exorbitant price of fish”, and current fashion (“Black gauze Cloaks are worn as much as anything”). She would go on to set parts of Northanger Abbey and Persuasion in the town which she described to her sister as being “all vapour, shadow, smoke & confusion”.

This letter is the earliest of the correspondence displayed in an exhibition at Cambridge University Library to mark the 200th anniversary of Austen’s death on 18 July 1817. ‘Jane Austen: Letters and Readers’ exhibits three manuscript letters held in Cambridge collections: the Fitzwilliam Museum, Cambridge University Library and King’s College. Only about 160 letters written by Austen survive worldwide.

‘Jane Austen: Letters and Readers’, which runs from 28 March to 8 April 2017, is a rare chance to view these precious letters along with other significant items relating to Austen in the University Library’s collection. It is the first time that the letters have been shown side by side.

The other two letters on display relate to the publication of Emma, Austen’s much-loved novel of 1816. An exchange of letters between Austen and Frances Parker, Countess of Morley, to whom Austen sent a copy of Emma, provides an insight into Austen’s contemporary readership.

Although Austen remained widely unknown during her lifetime and her novels were published anonymously, her reputation was growing, notably among aristocratic circles. In her letter to Austen, Frances Parker speaks of her intimacy with Austen’s characters, the “Bennetts [sic], Bertrams, Norriss & all their admirable predecessors”.

Frances Parker’s private responses give scholars valuable information as to how Austen’s work was being received. Elsewhere, the Countess testified to not liking Emma as much as Pride and Prejudice and Mansfield Park, because of its lack of story. Intriguingly, Parker herself was suspected by some to be the author of Austen’s fiction.

The last of the letters in the exhibition, dated 1 April 1816, is a short message from Austen to her publisher, the influential John Murray. In it, Austen discusses the novelist Walter Scott’s review of Emma, which was the first extended appreciation in print of Austen’s writing.

Scott recognised Austen’s innovative talent in “keeping close to common incidents, and to such characters as occupy the ordinary walks of life”. Austen also refers in this letter to another admirer, the Prince Regent, to whom the novel is (probably unwillingly) dedicated.

Alongside these letters, printed works are exhibited, including first editions of Austen’s fiction and items from the collection of Geoffrey Keynes, Austen’s bibliographer. A highlight from the Keynes collection is Oliver Goldsmith’s An History of the earth, and animated nature (1774), one of the few books known to have been owned by Jane Austen. Her signature inside the front cover, dated 1799, is on display.

The exhibition coincides with a conference at Trinity College (29-31 March 2017) to celebrate, in particular, the bicentenary of Sanditon, Jane Austen’s last, unfinished novel. The manuscript of Sanditon, which Austen was writing in the final year of her life, is held at King’s College. The last page is dated ‘March 18’. Austen died exactly four months later on 18 July 1817.

Participants in the conference will have the chance to see at King’s the manuscript of Sanditon, with other items from the College’s rich Jane Austen collection, including the manuscript continuation of the novel (in private ownership), written by Anna Lefroy, Austen’s niece. Lefroy was close to her aunt and received Austen’s literary advice. The two manuscripts are exhibited together for the first time.

Austen’s great-nephew Augustus Austen-Leigh was Provost of King’s between 1889 and 1905.  He married Florence Emma Lefroy, another Austen descendent (her great-great niece). Florence’s sister, Mary Isabella Lefroy, gave the manuscript of Sanditon to King’s in memory of “the most popular Provost, and Provostess “Kings” has ever had”.

‘Jane Austen: Letters and Readers’ runs from 28 March to 8 April 2017, 9am-6.30pm weekdays, 9am-5pm Saturdays, closed Sundays, in the entrance hall of Cambridge University Library. No charge.

For full details of the Trinity conference, events and registrations see: https://sanditon200years.wordpress.com.

As the Prime Minister signed the letter triggering Article 50 –the "divorce clause" in the EU treaties that provides the only legal route for the UK to withdraw from the EU— we reached the end of the beginning.

For nine months the UK and the EU have been in limbo. In the days and weeks following the June 2016 referendum, those who advocated leaving the EU were quick to claim that the much-heralded economic disasters threatened by George Osborne and David Cameron in “Project Fear” had not occurred.

Unhappy Remainers were equally swift in their rebuttals, as proponents of the two camps seemed determined to replay the arguments of their respective referendum campaigns – and in some cases the arguments of more than four decades.

Certainly, while the value of sterling might have dropped and inflation begun to rise, the economic indicators are far from the nightmare scenarios invoked during the referendum.  But that scenario was based on the idea that Cameron would trigger Article 50 immediately upon a Leave vote; in practice, he left the field, and his successor delayed the fateful act.

These last nine months have thus been little more than a phoney war.  The UK has barely begun to outline its negotiating objectives, while the other 27 member states made clear they would not engage in discussions before the UK formally indicated its intention to leave the Union. That day has now come.

The nature of the UK’s future relationship with the EU remains unclear, although the Prime Minister’s construal of the vote to leave the EU as a sign of popular support for curbing immigration has led to one clear red line: that the UK will not seek to remain in the single market.

This decision is perfectly rational and logical if one accepts the Prime Minister’s premise regarding the reasons 17 million people voted to leave, since free movement of people is a prerequisite of membership of the single market.

Yet, there is good cause to believe Mrs May is misguided in her interpretation: there were myriad reasons for the leave votes, whether to reclaim sovereignty or reduce payments to the EU,  all neatly encapsulated in the beguiling phrase “take back control”.

For many of those who voted leave, immigration and free movement were not the reason to seek EU withdrawal; even many Leavers acknowledge the importance of EU nationals to the UK economy.

To base a decision to leave the single market on the premise that we shall thereby "control" immigration is only a plausible thesis if those advocating it believe that Leave voters intended to prioritise controlling immigration numbers over the security of the economy, our agriculture and our welfare services, including the NHS and care of the elderly –all of which are heavily dependent upon immigrant labour.

Nonetheless, the Prime Minister appears to have adopted an approach that endears her to the hard Brexiteers in her own party, allowing a clean break from the EU, even if a majority in the country seems to favour a closer ongoing relationship with the 27.

For a city such as Cambridge, and for the University of Cambridge especially, membership of the single market with its associated rights of free movement is self-evidently beneficial. Many academics, myself included, have benefited over the years from EU funding – but what is at least as important is the opportunity to collaborate across borders, without having to consider whether a visa is needed.

EU nationals from other countries have played a vital role as students and colleagues. Even Brexiteers who wanted to reduce immigration were broadly in favour of guaranteeing the rights of EU nationals who were already in the UK at the time of the referendum.

Alongside many of us who would have preferred the UK not to be in the EU’s departure lounge, some of those Leavers have been demanding that the Government should give a unilateral undertaking to EU nationals already in the UK. The Government has said such people, along with UK nationals resident elsewhere in the EU, will be their first priority in the negotiations.

This is laudable, although it fails to comprehend a key facet of EU negotiations: nothing is agreed until everything is agreed.

The campaign to secure the rights of EU nationals will no doubt continue in the hope that some of the uncertainty engendered by the process of Brexit can be minimised, though the idea that some issues can be picked off and resolved in tranches is almost certainly fanciful.

Meanwhile, the withdrawal negotiations are likely to take the two years envisaged in the Lisbon Treaty – and that will only resolve the divorce settlement. For the longer term future arrangements with the 27, further, more protracted negotiations are likely.  Triggering Article 50 is not the end, though it would seem to herald the beginning of the end of the UK’s membership of the EU.

Dr Julie Smith is Director of the European Centre in the POLIS Department and a Liberal Democrat member of the House of Lords. Her new book, The UK’s Journeys Into and Out of the EU: Destinations Unknown, is published by Routledge. 

Writing in Science this week, the team, from the University of Cambridge, the University of East Anglia and the University of Eastern Finland, describes how it developed a new type of material that uses rotatable molecules to emit light faster than has ever been achieved before. It could lead to televisions, smart-phone displays and room lights which are more power-efficient, brighter and longer lasting than those currently on the market.

Corresponding author, Dr Dan Credgington, of the University of Cambridge’s Cavendish Laboratory, says:

“It’s amazing that the very first demonstration of this new kind of material already beats the performance of technologies which have taken decades to develop. If the effect we have discovered can be harnessed across the spectrum, it could change the way we generate light.”

Molecular materials are the driving force behind modern organic light-emitting diodes (OLEDs). Invented in the 1980s, these devices emit light when electricity is applied to the organic (carbon based) molecules in them. OLED lighting is now widely used in televisions, computers and mobile phones. However it has to overcome a fundamental issue which has limited efficiency when it comes to converting electrical energy into light.

Passing an electric current through these molecules puts them into an excited state, but only 25% of these are ‘bright’ states that can emit light rapidly. The remaining 75% are ‘dark’ states that usually waste their energy as heat limiting the efficiency of the OLED device. This mode of operation produces more heat than light just like in an old fashioned filament light bulb. The underlying reason is a quantum property called ‘spin’ and the dark states have the wrong type.

One approach to tackle this problem is to use rare elements, such as iridium, which help the dark states to emit light by allowing them to change their spin. The problem is this process takes too long, so the energy tied up in the dark states can build up to damaging levels and make the OLED unstable. This effect is such a problem for blue emitting materials (blue light has the highest energy of all the colours) that, in practice, the approach can’t be used. 

Dr Le Yang holding one of the most efficient OLED devices, developed in Cambridge 

Chemists at the University of East Anglia have now developed a new type of material where two different organic molecules are joined together by an atom of copper or gold. The resulting structure looks a bit like a propeller. The compounds, which can be made by a simple one-pot procedure from readily available materials, were found to be surprisingly luminescent. By rotating their “propeller”, dark states formed on these materials become twisted, which allows them to change their spin quickly. The process significantly increases the rate at which electrical energy is converted into light achieving an efficiency of almost 100% and preventing the damaging build-up of dark states.  

Dr Dawei Di and Dr Le Yang, from Cambridge, were co-lead authors long with Dr Alexander Romanov, from the UEA. He says:

“Our discovery that simple compounds of copper and gold can be used as bright and efficient materials for OLEDs demonstrates how chemistry can bring tangible benefits to society. All previous attempts to build OLEDs based on these metals have led to only mediocre success. The problem is that those materials required the sophisticated organic molecules to be bound with copper but has not met industrial standards. Our results address an on-going research and development challenge which can bring affordable high-tech OLED products to every home.”

Computational modelling played a major role in uncovering this novel way of harnessing intramolecular twisting motions for energy conversion.

Professor Mikko Linnolahti, of the University of Eastern Finland, where this was done, comments:

“This work forms the case study for how we can explain the principles behind the functioning of these new materials and their application in OLEDS.”

The next step is to design new molecules that take full advantage of this mechanism, with the ultimate goal of removing the need for rare elements entirely. This would solve the longest standing problem in the field – how to make OLEDs without having to trade-off between efficiency and stability.

Co-lead author, Dr Dawei Di, of the Cavendish Laboratory, says:

“Our work shows that excited-state spin and molecular motion can work together to strongly impact the performance of OLEDs. This is an excellent demonstration of how quantum mechanics, an important branch of fundamental science, can have direct consequences for a commercial application which has a massive global market.”

Reference:

Dawei Di et al: “High-performance light-emitting diodes based on carbene-metal-amides” is published in Science 30th March 2017

DOI 10.1126/science.aah4345