In an article in the journal Nature Reviews Clinical Oncology, a team of researchers jointly led by the University of Cambridge and University College London reviewed current evidence from 26 peer-reviewed studies and 6 online reports from 7 countries. The evidence indicates that emergency diagnosis of cancer is a universal problem, challenging previous assumptions regarding this issue being a particular problem only in the UK.

Looking at prognosis alone, the researchers reviewed evidence that showed that patients diagnosed with colorectal cancer at emergency presentation had a 50% one year survival rate, compared to 82% for patients diagnosed electively – in other words, following a GP referral to a specialist. Similarly, for lung cancer the respective survival rates were 12% versus 40%. This was in part because cancer diagnosed at emergency care was more likely to be at an advanced stage. However, this was not the full story: even when patients presented with tumours of the same disease stage they still had a worse prognosis if they were diagnosed in emergency care, possibly because of problems in the quality of their management out-of-hours, or because they have more aggressive disease on a stage-for-stage basis.

In the UK, about three in 10 emergency presenters are referred to hospital emergency services by their family doctors, but others self-present to accident and emergency departments. Patients at both ends of the age spectrum – the youngest and the oldest – were most likely to have their cancer diagnosed in emergency contexts. Differences between genders were unclear – and vary for different types of cancer.

However, the review found particular inequalities between socioeconomic groups. Although the evidence came only from studies looking at colorectal and lung cancer, it found that people from more deprived backgrounds were at a greater risk of being diagnosed at emergency care. The same was true for people of Asian ethnicity in the UK and African-Americans in the USA.

First author Dr Yin Zhou from the Primary Care Unit at the University of Cambridge, who led the study, says: “The earlier an individual can get a diagnosis of cancer, the better the prognosis and the options for treatment. When the first time their cancer is identified is when it becomes an emergency, the prognosis is much worse.”

Dr Georgios Lyratzopoulos, who instigated and coordinated the collaboration, based at the Department of Epidemiology and Public Health, University College London adds: “A substantial minority of cancer patients who are diagnosed as emergencies do not seem to have had prior contact with the formal healthcare system; we need to find out why they are not seeking medical help sooner. Is it because they are unaware of any symptoms until too late, or is it because they do not think the symptoms are a sign of a more serious problem?”

The researchers found that the evidence points towards developing new screening methods and improving participation in existing screening programme as one possible way to reduce emergency presentations in the medium to longer term. For example, based on indirect evidence in one geographical region in the UK, the introduction of faecal occult blood test in the UK is likely to have reduced the proportion of patients with colorectal cancer diagnosed as emergencies by half between 1999 and 2004.

“What was clear from our review,” adds Dr Zhou, “is how little data there is available about emergency diagnoses. What little data there is suggests that we’re only seeing the tip of the iceberg and that this could be a much bigger problem, particularly in low and middle income countries.”

A major part of the global evidence on emergency presentations (in terms of patient numbers) relates to English patients – thanks to the pioneering Routes to Diagnosis project and population-based data collected by the National Cancer Registration and Analysis Services of Public Health England.

Dr Anne Mackie, Director of Screening at Public Health England, said: “Screening has a vital role to play in identifying cancers at an early stage and getting people the right treatment as soon as possible, with better survival chances. Screening is always the person’s own choice and they should speak to their GP if they have any questions before deciding if screening is right for them.”
Reference
Zhou, Y et al. Diagnosis of cancer as an emergency: a critical review of current evidence. Nature Reviews Clinical Oncology; 11 Oct 2016; 10.1038/nrclinonc.2016.155

The Nobel Assembly made their announcement this morning (October 10), stating: “Modern economies are held together by innumerable contracts. The new theoretical tools created by Hart and Holmström are valuable to the understanding of real-life contracts and institutions, as well as potential pitfalls in contract design.

“Society’s many contractual relationships include those between shareholders and top executive management, an insurance company and car owners, or a public authority and its suppliers. As such relationships typically entail conflicts of interest, contracts must be properly designed to ensure that the parties take mutually beneficial decisions.

“This year’s laureates have developed contract theory, a comprehensive framework for analysing many diverse issues in contractual design, like performance-based pay for top executives, deductibles and co-pays in insurance, and the privatisation of public-sector activities.”

Professor Hart is currently the Andrew E. Furer Professor of Economics at Harvard University. From 1975 to 1981, Hart was an Assistant Lecturer and then Lecturer at the Faculty of Economics, and a Fellow of Churchill College. He was born in London in 1948 and gained his PhD from Princeton University in 1974.

In the mid-1980s, Oliver Hart made fundamental contributions to a new branch of contract theory that deals with the important case of incomplete contracts. Because it is impossible for a contract to specify every eventuality, this branch of the theory spells out optimal allocations of control rights: which party to the contract should be entitled to make decisions in which circumstances?

Hart’s findings on incomplete contracts have shed new light on the ownership and control of businesses and have had a vast impact on several fields of economics, as well as political science and law. His research provides us with new theoretical tools for studying questions such as which kinds of companies should merge, the proper mix of debt and equity financing, and when institutions such as schools or prisons ought to be privately or publicly owned.

Professor Hart becomes the 96th Cambridge affiliate to be awarded a Nobel Prize afterlast week’s Nobel Prize in Physics went to Cambridge alumni David Thouless (Trinity Hall, 1952), Duncan Haldane (Christ’s, 1970) and Michael Kosterlitz (Gonville and Caius, 1962).

More details on previous Cambridge winners can be found here:https://www.cam.ac.uk/research/research-at-cambridge/nobel-prize

Companies both depend upon and impact the environment, and are subject to interdependent pressures over food, energy, water and the environment. Yet their perspectives are often overlooked by the research community, which lacks access to their business thinking. Equally, businesses find it challenging to engage with the academic community, and to define researchable questions that would benefit from more detailed analysis.

The study, published in the journalSustainability Science and organised by the Cambridge Institute for Sustainability Leadership, included over 250 people, including academics and companies such as Asda, EDF Energy, HSBC and Nestlé, to produce research priorities that are both scientifically feasible and include results that can be practically implemented by the business community.

“The process of co-design engages businesses at the outset to help define the challenges, limitations and ambitions of research agendas. These considerations ultimately have important consequences for the impact and practicality of research outputs,” said lead author Dr Jonathan Green, formerly of the University of Cambridge’s Department of Geography. “Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation”.

The project is part of the work of the Nexus Network, an extensive network of researchers and stakeholders coordinated by the Cambridge Institute for Sustainability Leadership (CISL), the University of Sussex, the University of East Anglia, the University of Sheffield and the University of Exeter, and supported by the Economic and Social Research Council (ESRC).

The study was carried out over five months and involved researchers collecting over 700 questions from business practitioners, academics, policy-makers and members of the public. Over 50 per cent of these questions were submitted by businesses from a range of sectors, including retail, utilities, manufacturing and consumer goods. These questions were then reviewed by an expert group of businesses and researchers, who narrowed this list down to 40 questions that reflect key challenges for corporate sustainability.

Dr Bhaskar Vira, one of the project leads from the Department of Geography and the University of Cambridge Conservation Research Institute said: “We were able to bring together 40 experts with a huge diversity of backgrounds and knowledge. This unique group of senior business practitioners and interdisciplinary researchers, who represented 13 universities, 16 businesses and other important partners including ESRC, were able to inform the debate by their ability to answer both ‘Is this question answerable through an academic research project?’, but also ‘If answered, would this change the way we do business?”

Several themes emerged from the study, highlighting the issues that require more research and better engagement between the academic and business communities. These included research around development of pragmatic yet credible tools that allow businesses to incorporate the interactions between food, energy and water demands in a changing environment into their decision-making; the role of social considerations and livelihoods in business decision-making in relation to sustainable management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance on these issues.

“As pressures start to mount, placing enormous demands upon natural resources, we are increasingly asked for support by businesses who want practical approaches that they can apply to address their growing challenges,” said Dr Gemma Cranston, project lead from CISL. “Co-designing new research is critical to provide business with robust and rigorous approaches that are academically sound but that are also directly applicable to a business context. We have identified priority areas that can guide new research development and look forward to seeing a greater integration of businesses into collaborative research agendas.”

It will be the role of multi-disciplinary groups of researchers and business practitioners to devise the projects that will deliver the solutions to these pressing issues around food, energy, water and the environment.

Reference
Jonathan Green et al. ‘Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment.’ Sustainability Science (2016). DOI: 10.1007/s11625-016-0402-4

David Thouless (Trinity Hall, 1952), Duncan Haldane (Christ’s, 1970) and Michael Kosterlitz (Gonville and Caius, 1962) discovered unexpected behaviours of solid materials – and devised a mathematical framework to explain their properties. Their discoveries have led to new materials with an array of unique properties.

The Prize was divided, one half awarded to Thouless, the other half jointly to Haldane and Kosterlitz. The trio become the 93rd, 94th and 95th Nobel Affiliates of Cambridge to be awarded a Nobel Prize.

“This prize is richly deserved,” said Professor Nigel Cooper of Cambridge’s Cavendish Laboratory. “Through the great breakthroughs they’ve made, Thouless, Haldane and Kosterlitz took a visionary approach to understanding how topology plays a role in novel materials.”

Topology is a mathematical concept that accounts for how certain physical properties are related by smooth deformations: a football can be smoothly deformed into a rugby ball (so these have the same topology), but neither of these can be smoothly deformed into a bicycle tube (which therefore has different topology). The Laureates recognized how novel states of matter could arise due to the differing topologies of how the underlying particles arrange themselves at the microscopic level.

The Nobel Assembly made their announcement this morning (October 4), saying: “This year’s Laureates opened the door on an unknown world where matter can assume strange states. They have used advanced mathematical methods to study unusual phases, or states, of matter, such as superconductors, superfluids or thin magnetic films. Thanks to their pioneering work, the hunt is now on for new and exotic phases of matter. Many people are hopeful of future applications in both materials science and electronics.

“The three Laureates’ use of topological concepts in physics was decisive for their discoveries. Topology is a branch of mathematics that describes properties that only change step-wise. Using topology as a tool, they were able to astound the experts. In the early 1970s, Michael Kosterlitz and David Thouless overturned the then current theory that superconductivity or suprafluidity could not occur in thin layers. They demonstrated that superconductivity could occur at low temperatures and also explained the mechanism, phase transition, that makes superconductivity disappear at higher temperatures.

“In the 1980s, Thouless was able to explain a previous experiment with very thin electrically conducting layers in which conductance was precisely measured as integer steps. He showed that these integers were topological in their nature. At around the same time, Duncan Haldane discovered how topological concepts can be used to understand the properties of chains of small magnets found in some materials.

“We now know of many topological phases, not only in thin layers and threads, but also in ordinary three-dimensional materials. Over the last decade, this area has boosted frontline research in condensed matter physics, not least because of the hope that topological materials could be used in new generations of electronics and superconductors, or in future quantum computers. Current research is revealing the secrets of matter in the exotic worlds discovered by this year’s Nobel Laureates.”

Professor Haldane is the current Eugene Higgins Professor of Physics at Princeton University. Born in London in 1951, he came to Christ’s as an undergraduate in 1970 to read Natural Sciences. His PhD was conferred in 1978.

Professor Kosterlitz is the Harrison E. Farnsworth Professor of Physics at Brown University, where he joined the faculty in 1982. He was born to German Jewish emigres in 1942 and his father was the pioneering biochemist Hans Walter Kosterlitz. Professor Kosterlitz, who came to Cambridge in 1965, is the 14th Nobel Laureate affiliated to Gonville and Caius.

Professor Thouless, born in 1934, is Emeritus Professor of Physics at the University of Washington. An undergraduate at Trinity Hall, he was also previously a Visiting Fellow at Clare Hall, where he was awarded a Doctorate of Science in 1985. He has been a Life Member of the college since 1986.

Professor Thouless was also a Fellow of Churchill College from 1961-65, and in 1961 became its first Director of Studies for Physics. He has also held the position of Visiting Fellow at Churchill. He is Churchill’s 31st Nobel Affiliate and Trinity Hall’s first.

The Master of Caius, Professor Sir Alan Fersht, today warmly congratulated Prof Kosterlitz, who was his exact contemporary at Caius, coming up to Cambridge to read Natural Sciences in 1962. “This is fantastic news,” Sir Alan said. “Mike was obviously an exceptionally clever guy. We went to physics lectures together in our first year, and he continued to specialise in Physics in the second year while I specialised in Chemistry. He was a very good physicist, and moved from the UK to America fairly rapidly.

“He was an absolutely mad climber – he disappeared every weekend to go mountain climbing in the Peak District. He lived on Tree Court, and he built a traverse around the room where he would climb using his fingers and hanging on to the picture rail.”

More details on previous Cambridge winners can be found here:https://www.cam.ac.uk/research/research-at-cambridge/nobel-prize.

The first Nobel Prize in Physics was awarded in 1901.

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It all started at Caius… Co-winner of 2016 #NobelPrize for#Physics Michael Kosterlitz in his Matriculation photo at Caius in 1962

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Carrick Therapeutics Ltd, a company which is developing new treatments for the most aggressive and resistant forms of cancer, launched today having secured $95 million in funding, representing the largest early-stage investment in a UK university spin-out.

The company, which has licensed technology developed at the Gurdon Institute at the University of Cambridge, brings together cancer researchers and drug development experts, backed by leading providers of early stage funding, with the aim of building Europe’s leading oncology company.

Carrick Therapeutics has research and development teams located in Dublin and Oxford. The $95 million funding round was led by ARCH Venture Partners and Woodford Investment Management with participation from Cambridge Enterprise Seed Funds, Cambridge Innovation Capital, Evotec AG, GV (Google Ventures) and Lightstone Ventures.

The first technology licensed by the company was developed at the Gurdon Institute and was licensed by Cambridge Enterprise, the University’s technology transfer arm. Carrick received seed funding in 2015 from ARCH Venture Partners and Cambridge Enterprise Seed Funds.

“This investment and in particular the scale of the investment marks a real turning point for investments in Cambridge spin-out companies,” said Bradley Hardiman, Investment Manager for Cambridge Enterprise Seed Funds. “In the past, particularly in Europe, investors have been guilty of drip-feeding money in to companies. This means that companies could be continuously fundraising, distracting them from the critical task of advancing treatments. This ‘war chest’ of funding will enable Carrick to get on with the important work of researching and developing new cancer treatments, making real differences to sufferers of this debilitating disease.”

The company’s vision is to target the molecular pathways that drive the most aggressive and resistant forms of cancer. While other companies are often reliant on a single compound or biological mechanism, Carrick Therapeutics is building a portfolio of treatments that are progressed through understanding the mechanisms that cause cancer and resistance, and are tailored to an individual patient’s tumour.

By linking a network of clinicians and scientists in internationally leading research institutes and hospitals, Carrick will move its portfolio of ground-breaking cancer therapies from laboratory to clinic.

“Our aim is to build Europe’s leading oncology company,” said Carrick Chief Executive Dr Elaine Sullivan, a former Vice President for research and development functions at both Eli Lilly and AstraZeneca. “There is a significant unmet need in cancer treatment, and targeting aggressive and resistant disease is an area where we can make a real difference to patients’ lives.”

Carrick Therapeutics is working on three innovative scientific programmes, and is looking to expand its portfolio through academic and pharmaceutical partnerships.

The company’s worldwide network of collaborating cancer experts includes the world’s leading cancer research charity, Cancer Research UK, and researchers from several of the world’s top universities, including Cambridge, Imperial College London and Oxford.

“The quality of the science and assets, combined with the calibre of the management team makes Carrick Therapeutics a powerful proposition,” said Steven Gillis, Managing Partner of ARCH Venture Partners and a member of the board of Carrick Therapeutics. “As an investor and a scientist I look forward to Carrick Therapeutics being a dominant force in the fight against cancer.”

Adapted from a Cambridge Enterprise press release. 

Subject to the approval of the Regent House, the University’s governing body, Professor Toope will take over from Professor Sir Leszek Borysiewicz on 1 October 2017.

Professor Toope is Director of the University of Toronto’s Munk School of Global Affairs and formerly served as president and vice-chancellor of the University of British Columbia.

He is a scholar specialising in human rights, international dispute resolution, international environmental law, the use of force, and international legal theory with degrees in common law (LLB) and civil law (BCL) with honours from McGill University (1983). Professor Toope is also an alumnus of Trinity College Cambridge, where he completed his PhD in 1987.

He graduated from Harvard with a degree (AB) in history and literature in 1979. He has published articles and books on change in international law, and the origins of international obligation in international society.

Professor Toope also represented Western Europe and North America on the UN Working Group on Enforced or Involuntary Disappearances from 2002-2007.

Cambridge has carried out an international search for the position of Vice-Chancellor and the Search Committee was headed up by the Master of Jesus College, Professor Ian White.

Professor White said: “This nomination builds on seven years of Sir Leszek’s visionary leadership. Professor Toope has impeccable academic credentials, a longstanding involvement with higher education, strong leadership experience and an excellent research background.”

Vice-Chancellor Professor Sir Leszek Borysiewicz says, “We are delighted to be welcoming a distinguished leader with such an outstanding record as a scholar and educator to lead Cambridge.”

Professor Toope says, “I am thrilled to be returning to this great university. I look forward to working with staff and students in the pursuit of academic excellence and tremendous international engagement – the very mark of Cambridge.”

Professor Sir Leszek Borysiewicz will continue to lead the University until Professor Toope takes up his post on 1 October 2017.

The first major genomic study of Aboriginal Australians ever undertaken has confirmed that all present-day non-African populations are descended from the same single wave of migrants, who left Africa around 72,000 years ago.

Researchers sequenced the complete genetic information of 83 Aboriginal Australians, as well as 25 Papuans from New Guinea, to produce a host of significant new findings about the origins of modern human populations. Their work is published alongside several other related papers in the journal Nature.

The study, by an international team of academics, was carried out in close collaboration with elders and leaders from various Aboriginal Australian communities – some of whom are co-authors on the paper – as well as with various other organisations representing the participating groups.

Alongside the prevailing conclusion, that the overwhelming majority of the genomes of non-Africans alive today stem from one ancestral group of migrants who left Africa together, there are several other standout findings. These include:

• Compelling evidence that Aboriginal Australians are descended directly from the first people to inhabit Australia – which is still the subject of periodic political dispute.
• Evidence of an uncharacterised – and perhaps unknown – early human species which interbred with anatomically modern humans as they migrated through Asia.
• Evidence that a mysterious dispersal from the northeastern part of Australia roughly 4,000 years ago contributed to the cultural links between Aboriginal groups today. These internal migrants defined the way in which people spoke and thought, but then disappeared from most of the continent, in a manner which the researchers describe as “ghost-like”.

The study’s senior authors are from the University of Cambridge, the Wellcome Trust Sanger Institute, the Universities of Copenhagen, Bern and Griffith University Australia. Within Cambridge, members of the Leverhulme Centre for Evolutionary Studies also contributed to the research, in particular by helping to place the genetic data which the team gathered in the field within the context of wider evidence about early human population and migration patterns.

Professor Eske Willerslev, who holds posts at St John’s College, University of Cambridge, the Sanger Institute and the University of Copenhagen, initiated and led the research. He said: “The study addresses a number of fundamental questions about human evolution – how many times did we leave Africa, when was Australia populated, and what is the diversity of people in and outside Australia?”

“Technologically and politically, it has not really been possible to answer those questions until now. We found evidence that there was only really one wave of humans who gave rise to all present-day non-Africans, including Australians.”

Anatomically modern humans are known to have left Africa approximately 72,000 years ago, eventually spreading across Asia and Europe. Outside Africa, Australia has one of the longest histories of continuous human occupation, dating back about 50,000 years.

Some researchers believe that this deep history indicates that Papuans and Australians stemmed from an earlier migration than the ancestors of Eurasian peoples; others that they split from Eurasian progenitors within Africa itself, and left the continent in a separate wave.

Until the present study, however, the only genetic evidence for Aboriginal Australians, which is needed to investigate these theories, came from one tuft of hair (taken from a long-since deceased individual), and two unidentified cell lines.

The new research dramatically improves that picture. Working closely with community elders, representative organisations and the ethical board of Griffith University, Willerslev and colleagues obtained permission to sequence dozens of Aboriginal Australian genomes, using DNA extracted from saliva.

This was compared with existing genetic information about other populations. The researchers modelled the likely genetic impact of different human dispersals from Africa and towards Australia, looking for patterns that best matched the data they had acquired. Dr Marta Mirazon Lahr and Professor Robert Foley, both from the Leverhulme Centre, assisted in particular by analysing the likely correspondences between this newly-acquired genetic evidence and a wider framework of existing archaeological and anthropological evidence about early human population movements.

Dr Manjinder Sandhu, a senior author from the Sanger Institute and University of Cambridge, said: “Our results suggest that, rather than having left in a separate wave, most of the genomes of Papuans and Aboriginal Australians can be traced back to a single ‘Out of Africa’ event which led to modern worldwide populations. There may have been other migrations, but the evidence so far points to one exit event.”

The Papuan and Australian ancestors did, however, diverge early from the rest, around 58,000 years ago. By comparison, European and Asian ancestral groups only become distinct in the genetic record around 42,000 years ago.

The study then traces the Papuan and Australian groups’ progress. Around 50,000 years ago they reached “Sahul” – a prehistoric supercontinent that originally united New Guinea, Australia and Tasmania, until these regions were separated by rising sea levels approximately 10,000 years ago.

The researchers charted several further “divergences” in which various parts of the population broke off and became genetically isolated from others. Interestingly, Papuans and Aboriginal Australians appear to have diverged about 37,000 years ago – long before they became physically separated by water. The cause is unclear, but one reason may be the early flooding of the Carpentaria basin, which left Australia connected to New Guinea by a strip of land that may have been unfavourable for human habitation.

Once in Australia, the ancestors of today’s Aboriginal communities remained almost completely isolated from the rest of the world’s population until just a few thousand years ago, when they came into contact with some Asian populations, followed by European travellers in the 18th Century.

Indeed, by 31,000 years ago, most Aboriginal communities were genetically isolated from each other. This divergence was most likely caused by environmental barriers; in particular the evolution of an almost impassable central desert as the Australian continent dried out.

Assistant Professor Anna-Sapfo Malaspinas, from the Universities of Copenhagen and Bern, and a lead author, said: “The genetic diversity among Aboriginal Australians is amazing. Because the continent has been populated for such a long time, we find that groups from south-western Australia are genetically more different from north-eastern Australia, than, for example, Native Americans are from Siberians.”

Two other major findings also emerged. First, the researchers were able to reappraise traces of DNA which come from an ancient, extinct human species and are found in Aboriginal Australians. These have traditionally been attributed to encounters with Denisovans – a group known from DNA samples found in Siberia.

In fact, the new study suggests that they were from a different, as-yet uncharacterised, species. “We don’t know who these people were, but they were a distant relative of Denisovans, and the Papuan/Australian ancestors probably encountered them close to Sahul,” Willerslev said.

Finally, the research also offers an intriguing new perspective on how Aboriginal culture itself developed, raising the possibility of a mysterious, internal migration 4,000 years ago.

About 90% of Aboriginal communities today speak languages belonging to the “Pama-Nyungan” linguistic family. The study finds that all of these people are  descendants of the founding population which diverged from the Papuans 37,000 years ago, then diverged further into genetically isolated communities.

This, however, throws up a long-established paradox. Language experts are adamant that Pama-Nyungan languages are much younger, dating back 4,000 years, and coinciding with the appearance of new stone technologies in the archaeological record.

Scientists have long puzzled over how – if these communities were completely isolated from each other and the rest of the world – they ended up sharing a language family that is much younger? The traditional answer has been that there was a second migration into Australia 4,000 years ago, by people speaking this language.

But the new research finds no evidence of this. Instead, the team uncovered signs of a tiny gene flow, indicating a small population movement from north-east Australia across the continent, potentially at the time the Pama-Nyungan language and new stone tool technologies appeared.

These intrepid travellers, who must have braved forbidding environmental barriers, were small in number, but had a significant, sweeping impact on the continent’s culture. Mysteriously, however, the genetic evidence for them then disappears. In short, their influential language and culture survived – but they, as a distinctive group, did not.

“It’s a really weird scenario,” Willerslev said. “A few immigrants appear in different villages and communities around Australia. They change the way people speak and think; then they disappear, like ghosts. And people just carry on living in isolation the same way they always have. This may have happened for religious or cultural reasons that we can only speculate about. But in genetic terms, we have never seen anything like it before.”

The paper, A Genomic History of Aboriginal Australia, is published in Nature. doi:10.1038/nature18299.

Inset images: Professor Eske Willerslev talking to Aboriginal elders in the Kalgoorlie area in southwestern Australia in 2012. (Photo credit: Preben Hjort, Mayday Film). / Map showing main findings from the paper. Credit: St John’s College, Cambridge.

Social businesses – those with a socially beneficial objective – can play an important role in developing countries in addressing needs such as healthcare, energy, education and sanitation, but such businesses have faced a difficult time scaling up to significant size and reach.

A new study by researchers from Cambridge University has identified four key strategies and two methods for social businesses to scale up, which could help them reach many more of the four billion people in developing countries who could benefit from the services of such businesses.

Meeting these needs through affordable and sustainable solutions offers businesses a vast opportunity for future growth. As developing markets emerge from low-income to middle-income status, their development offers businesses the potential to make profits while also delivering significant social impact.

The study, published in the Journal of Cleaner Production, identifies market penetration, market development, product development and diversification as the four key growth strategies at different stages of business maturity for social businesses. In parallel, the study found two ways of increasing income generated through these four strategies – increasing revenue per stream and diversifying revenue streams.

Previous studies in this area had focused on scaling up conventional for-profit businesses and NGOs, but there had been little research on scaling up profit-generating social businesses.

Social businesses have had difficulty scaling up in developing countries due to a lack of infrastructure such as roads and electricity, coupled with a lack of clear property rights and well-functioning courts. On a more encouraging note, new technology such as mobile phones and new business structures such as public-private partnerships now make it easier for such businesses to find ways to reach new consumers.

“Social businesses have enormous potential to provide important services to billions of people around the world – but they need to scale up in order to meet these needs,” said study co-author Professor Jaideep Pradhu from Cambridge Judge Business School. “This study is a first step to greater understanding in this area, but we need a lot more work to support the development and growth of such businesses.”

The study focused on three successful social businesses – development organization BRAC, eye care company Aravind and Amul Dairy.

BRAC, one of the world’s largest NGOs, serving 135 million people in 11 countries in areas ranging from nutrition and sanitation to microfinance, uses “replication and diffusion” as a key to its successful efforts to scale up. To reach people in dispersed regions, for example, BRAC used village societies and village intermediaries to train people, testing solutions in local communities and improving them before expanding to larger communities.

Aravind Eye Care runs a number of hospitals and eye care centres in India, treating more than three million people a year to fight blindness in the country. In order to scale up, Aravind chose to increase the number of hospitals and centres in a given region – and then diversified activities by adding a manufacturing unit, staff training and a research department.

Amul Dairy, an Indian co-operative of three million milk producers, began to scale up by increasing the number of milk producers in the state of Gujurat followed by establishment of a processing plant to produce dairy products from excess milk. A partnership with the government then helped Amul to expand across India and into other countries.

All three companies used almost all the different scaling-up methods at one point in their development, suggesting that all strategies are important to achieve scale and that companies need to mix and match different strategies.

Based on the case studies, companies with a clear single purpose (Aravind and Amul) might start with ‘simpler’ strategies such as market penetration, while companies like BRAC with broader goals will need a more diverse approach.

Reference:
Nancy M.P. Bocken, Alison Fil, and Jaideep Prabhu. ‘Scaling up social businesses in developing markets.’ Journal of Cleaner Production (2016). DOI:10.1016/j.jclepro.2016.08.045

Adapted from a Cambridge Judge Business School press release.

Researchers have developed an algorithm that aids our understanding of how living systems work, by identifying which proteins within cells will interact with each other, based on their genetic sequences alone.

The ability to generate huge amounts of data from genetic sequencing has developed rapidly in the past decade, but the trouble for researchers is in being able to apply that sequence data to better understand living systems. The new research, published in the journal Proceedings of the National Academy of Sciences, is a significant step forward because biological processes, such as how our bodies turn food into energy, are driven by specific protein-protein interactions.

“We were really surprised that our algorithm was powerful enough to make accurate predictions in the absence of experimentally-derived data,” said study co-author Dr Lucy Colwell, from the University of Cambridge’s Department of Chemistry, who led the study with Ned Wingreen of Princeton University. “Being able to predict these interactions will help us understand how proteins fit and work together to complete required tasks – and using an algorithm is much faster and much cheaper than relying on experiments.”

When proteins interact with each other, they stick together to form protein complexes. In her previous research, Colwell found that if the two interacting proteins were known, sequence data could be used to figure out the structure of these complexes. Once the structure of the complexes is known, researchers can then investigate what is happening chemically. However, the question of which proteins interact with each other still required expensive, time-consuming experiments. Each cell often contains multiple versions of the same protein, and it wasn’t possible to predict which version of each protein would interact specifically – instead, experiments involve trying all options to see which ones stick.

In the current paper, the researchers used a mathematical algorithm to sift through the possible interaction partners and identify pairs of proteins that interact with each other. The method correctly predicted 93% of protein-protein interactions present in a dataset of more than 40,000 protein sequences for which the pairing is known, without being first provided any examples of correct pairs.

When two proteins stick together, some amino acids on one chain stick to the amino acids on the other chain. The boundaries between interacting proteins tend to evolve together over time, causing their sequences to mirror each other.

The algorithm uses this effect to build a model of the interaction. It first randomly pairs protein versions within each organism – because interacting pairs tend to be more similar in sequence to one another than non-interacting pairs, the algorithm can quickly identify a small set of largely correct pairings from the random starting point.

Using this small set, the algorithm measures whether the amino acid at a particular location in the first protein influences which amino acid occurs at a particular location in the second protein. These dependencies, learned from the data, are incorporated into a model and used to calculate the interaction strengths for each possible protein pair. Low-scoring pairings are eliminated, and the remaining set used to build an updated model.

The researchers thought that the algorithm would only work accurately if it first ‘learned’ what makes a good protein-protein pair by studying pairs that have been discovered in experiments. This meant that the researchers had to give the algorithm some known protein pairs, or ‘gold standards,’ against which to compare new sequences. The team used two well-studied families of proteins, histidine kinases and response regulators, which interact as part of a signaling system in bacteria.

But known examples are often scarce, and there are tens of millions of undiscovered protein-protein interactions in cells. So the team decided to see if they could reduce the amount of training they gave the algorithm. They gradually lowered the number of known histidine kinase-response regulator pairs that they fed into the algorithm, and were surprised to find that the algorithm continued to work. Finally, they ran the algorithm without giving it any such training pairs, and it still predicted new pairs with 93 percent accuracy.

“The fact that we didn’t need a set of training data was really surprising,” said Colwell.

The algorithm was developed using proteins from bacteria, and the researchers are now extending the technique to other organisms. “Reactions in living organisms are driven by specific protein interactions,” said Colwell. “This approach allows us to identify and probe these interactions, an essential step towards building a picture of how living systems work.”

The research was supported in part by the National Institutes of Health, the National Science Foundation and the European Union.

Reference:
Anne-Florence Bitbol et al. ‘Inferring interaction partners from protein sequences.’ Proceedings of the National Academy of Sciences (2016). DOI:10.1073/pnas.1606762113

‘Gut feelings’ – known technically as interoceptive sensations – are sensations that carry information to the brain from many tissues of the body, including the heart and lungs, as well as the gut. They can report anything from body temperature to breathlessness, racing heart, fullness from the gut, bladder and bowel, and they underpin states such as hunger, thirst, pain, and anxiety.

We are often not conscious – or at least barely aware – of this information, but it provides valuable inputs in risky decision making. High-risk choices are accompanied by rapid and subtle physiological changes that feed back to the brain, affecting our decisions, and steering us away from gambles that are likely to lead to loss and towards those that are likely to lead to profit. This can enable people to make important decisions even before they are able to articulate the reasons for their choices.

Traders and investors in the financial markets frequently talk of the importance of gut feelings for selecting profitable trades. To find out the extent to which this belief is correct, researchers from the Universities of Cambridge and Sussex in the UK and Queensland University of Technology in Australia compared the interoceptive abilities of financial traders against those of non-trader control subjects. Their results are published today in the journal Scientific Reports.

The researchers recruited 18 male traders from a hedge fund engaged in high frequency trading, which involves buying and selling futures contracts for only a short period of time – seconds or minutes, a few hours at the most. This form of trading requires an ability to assimilate large amounts of information flowing through news feeds, to rapidly recognize price patterns, and to make large and risky decisions with split-second timing. This niche of the financial markets is particularly unforgiving: while successful traders may earn in excess of £10 million per year, unprofitable ones do not survive for long.

The study took place during a particularly volatile period – the Eurozone crisis – so the performance of each trader reflected his ability to make money during periods of extreme uncertainty. The researchers measured individual differences in each trader’s capacity to detect subtle changes in the physiological state of their bodies by means of two established heartbeat detection tasks. These tasks test how accurately a person, when at rest, can count their heartbeats. Each trader was given a score which, essentially, measured the percentage of right answers, and these scores were compared against data from 48 students at the University of Sussex.

The researchers found that traders performed significantly better at the heart rate detection tasks compared to the controls: the mean score for traders was 78.2, compared to 66.9 for the controls. Even within the group of traders, those who were better at the heart rate detection tasks also performed better at trading, generating greater profits.

Strikingly, an individual’s interoceptive ability could be used to predict whether they would survive in the financial markets. The researchers plotted heartbeat detection scores against years of experience in the financial markets and found that a trader’s heartbeat counting score predicted the number of years he had survived as a trader.

“Traders in the financial world often speak of the importance of gut feelings for choosing profitable trades – they select from a range of possible trades the one that just ‘feels right’,” says Dr John Coates, a former research fellow in neuroscience and finance at the University of Cambridge, who also used to run a trading desk on Wall Street. “Our findings suggest they’re right – they manage to read real and valuable physiological trading signals, even if they are unaware they are doing so.”

Although the results are consistent with recent studies showing that heartbeat detection skills predict more effective risk taking, the researchers caution that there may be other interpretations. For example, one study has found that heartbeat detection ability increases during stress, so it could be argued that heartbeat detection skills correlated with years of survival merely because experienced traders, taking larger risks, are subjected to greater stresses. The authors of the current study think this unlikely – in trading, as in many other professions, experienced and successful individuals, being more in control, are commonly less stressed than beginners.

The findings also appear to contradict the influential ‘Efficient Markets Hypothesis’ of economic theory, which argues that the market is random, meaning that no trait or skill of an investor or trader – not their IQ, education, nor training – can improve their performance, any more than these traits and skills could improve their performance at flipping coins.

“A large part of a trader’s success and survival seems to be linked to their physiology. Such a finding has profound implications for how we understand financial markets,” adds Dr Mark Gurnell from the Wellcome Trust-Medical Research Council Institute of Metabolic Science at the University of Cambridge.

“In economics and finance most models analyse conscious reasoning and are based on psychology,” Dr Coates continues. “We’re looking instead at risk takers’ physiology – how good are they at sensing signals from their viscera? We should refocus on the body, or more exactly the interaction between body and brain. Medics find this obvious; economists don’t.”

The research was largely funded by the Economic and Social Research Council, the European Research Council and the Dr Mortimer and Theresa Sackler Foundation. Additional support was provided by the National Institute for Health Research Cambridge Biomedical Research Centre.

Reference
Kandasamy, N, Garfinkel, SN, Page, L et al. Interoceptive Ability Predicts Survival on a London Trading Floor. Scientific Reports; 19 Sept 2016; DOI: 10.1038/srep32986

Scientists have found that developing nerve cells are able to ‘feel’ their environment as they grow, helping them form the correct connections within the brain and with other parts of the body. The results, reported in the journal Nature Neuroscience, could open up new avenues of research in brain development, and lead to potential treatments for spinal cord injuries and other types of neuronal damage.

As the brain develops, roughly 100 billion neurons make over 100 trillion connections to send and receive information. For decades, it has been widely accepted that neuronal growth is controlled by small signalling molecules which are ‘sniffed’ out by the growing neurons, telling them which way to go, so that they can find their precise target. The new study, by researchers from the University of Cambridge, shows that neuronal growth is not only controlled by these chemical signals, but also by the physical properties of their environment, which guide the neurons along complex stiffness patterns in the tissue through which they grow.

“The fact that neurons in the developing brain not only respond to chemical signals but also to the mechanical properties of their environment opens many exciting new avenues for research in brain development,” said the study’s lead author Dr Kristian Franze, from Cambridge’s Department of Physiology, Development and Neuroscience. “Considering mechanics might also lead to new breakthroughs in our understanding of neuronal regeneration. For example, following spinal cord injuries, the failure of neurons to regrow through damaged tissue with altered mechanical properties has been a persistent challenge in medicine.”

We navigate our world guided by our senses, which are based on interactions with different facets of our environment — at the seaside you smell and taste the saltiness of the air, feel the grains of sand and the coldness of the water, and hear the crashing of waves on the beach. Within our bodies, individual neurons also sense and react to their environment – they ‘taste’ and ‘smell’ small chemical molecules, and, as this study shows, ‘feel’ the stiffness and structure of their surroundings. They use these senses to guide how and where they grow.

Using a long, wire-like extension called an axon, neurons carry electrical signals throughout the brain and body. During development, axons must grow along precisely defined pathways until they eventually connect with their targets. The enormously complex networks that result control all body functions. Errors in the neuronal ‘wiring’ or catastrophic severing of the connections, as occurs during spinal cord injury, may lead to severe disabilities.

A number of chemical signals controlling axon growth have been identified. Called ‘guidance cues,’ these molecules are produced by cells in the tissue surrounding growing axons and may either attract or repel the axons, directing them along the correct paths. However, chemical guidance cues alone cannot fully explain neuronal growth patterns, suggesting that other factors contribute to guiding neurons.

One of these factors turns out to be mechanics: axons also possess a sense of ‘touch’. In order to move, growing neurons must exert forces on their environment. The environment in turn exerts forces back, and the axons can therefore ‘feel’ the mechanical properties of their surroundings, such as its stiffness. “Consider the difference between walking on squelchy mud versus hard rock – how you walk, your balance and speed, will differ on these two surfaces,” said Franze. “Similarly, axons adjust their growth behaviour depending on the mechanical properties of their environment.” However, until recently it was not known what environments axons encounter as they grow, and Franze and his colleagues decided to find out.

They developed a new technique, based on atomic force microscopy, to measure the stiffness of developing Xenopus frog brains at high resolution – revealing what axons might feel as they grow through the brain. The study found complex patterns of stiffness in the developing brain that seemed to predict axon growth directions. The researchers showed that axons avoided stiffer areas of the brain and grew towards softer regions. Changing the normal brain stiffness caused the axons to get lost and fail to find their targets.

In collaboration with Professor Christine Holt’s research group, the team then explored how exactly the axons were feeling their environments. They found that neurons contain ion channels called Piezo1, which sit in the cell membrane: the barrier between cell and environment. These channels open only when a large enough force is applied, similar to shutter valves in air mattresses. Opening of these channels generates small pores in the membrane of the neurons, which allows calcium ions to enter the cells. Calcium then triggers a number of reactions that change how neurons grow.

When neuronal membranes were stiffened using a substance extracted from a spider venom, which made it harder to open the channels, neurons became ‘numb’ to environmental stiffness. This caused the axons to grow abnormally without reaching their target. Removing Piezo1 from the cells, similarly abolishing the axons’ capacity to feel differences in stiffness, had the same effect.

“We already understand quite a bit about the detection and integration of chemical signals” said Franze. “Adding mechanical signals to this picture will lead to a better understanding of the growth and development of the nervous system. These insights will help us answer critical questions in developmental biology as well as in biomedicine and regenerative biology.”

Reference:
David E Koser et al. ‘Mechanosensing is critical for axon growth in the developing brain.’ Nature Neuroscience (2016). DOI: 10.1038/nn.4394

Scientists have controlled electrons by packing them so tightly that they start to display quantum effects, using an extension of the technology currently used to make computer processors. The technique, reported in the journal Nature Communications, has uncovered properties of quantum matter that could pave a way to new quantum technologies.

The ability to control electrons in this way may lay the groundwork for many technological advances, including quantum computers that can solve problems fundamentally intractable by modern electronics. Before such technologies become practical however, researchers need to better understand quantum, or wave-like, particles, and more importantly, the interactions between them.

Squeezing electrons into a one-dimensional ‘quantum wire’ amplifies their quantum nature to the point that it can be seen, by measuring at what energy and wavelength (or momentum) electrons can be injected into the wire.

“Think of a crowded train carriage, with people standing tightly packed all the way down the centre of the carriage,” said Professor Christopher Ford of the University of Cambridge’s Cavendish Laboratory, one of the paper’s co-authors. “If someone tries to get in a door, they have to push the people closest to them along a bit to make room. In turn, those people push slightly on their neighbours, and so on. A wave of compression passes down the carriage, at some speed related to how people interact with their neighbours, and that speed probably depends on how hard they were shoved by the person getting on the train. By measuring this speed, one could learn about the interactions.”

“The same is true for electrons in a quantum wire – they repel each other and cannot get past, so if one electron enters or leaves, it excites a compressive wave like the people in the train,” said the paper’s first author Dr Maria Moreno, also from the Cavendish Laboratory.

However, electrons have another characteristic, their angular momentum or ‘spin’, which also interacts with their neighbours. Spin can also set off a wave carrying energy along the wire, and this spin wave travels at a different speed to the charge wave. Measuring the wavelength of these waves as the energy is varied is called tunnelling spectroscopy. The separate spin and charge waves were detected experimentally by researchers from Harvard and Cambridge Universities.

Now, in the paper published in Nature Communications, the Cambridge researchers have gone one stage further, to test the latest predictions of what should happen at high energies, where the original theory breaks down.

A flurry of theoretical activity in the past decade has led to new predictions of other ways of exciting waves among the electrons — it’s as if the person entering the train pushes so hard some people fall over and knock into others much further down the carriage. These new ‘modes’ are weaker than the spin and charge waves and so are harder to detect.

The collaborators of the Cambridge researchers from the University of Birmingham predicted that there would be a hierarchy of modes corresponding to the variety of ways in which the interactions can affect the quantum-mechanical particles, and the weaker modes should be strongest in very short wires.

To make a set of such short wires, the Cambridge group set about devising a way of making contact to a set of 6000 narrow strips of metal that are used to create the quantum wires from the semiconducting material gallium arsenide (GaAs). This required an extra layer of metal in the shape of bridges between the strips.

By varying the magnetic field and voltage, the tunnelling from the wires to an adjacent sheet of electrons could be mapped out, and this revealed evidence for the extra curves predicted, where it can be seen as an upside-down replica of the spin curve.

These results will now be applied to better understand and control the behaviour of electrons in the building blocks of a quantum computer.

Reference:
Moreno et al. ‘Nonlinear spectra of spinons and holons in short GaAs quantum wires.’ Nature Communications (2016).DOI: 10.1038/ncomms12784 

Detailed information about more than a billion stars in the Milky Way has been published in the first data release from the Gaia satellite, which is conducting the first-ever ‘galactic census.’ The release marks the first chance astronomers and the public have had to get their hands on the most detailed map ever made of the sky.

Gaia, which orbits the sun at a distance of 1.5 million kilometres from the earth, was launched by the European Space Agency in December 2013 with the aim of observing a billion stars and revolutionising our understanding of the Milky Way. During its expected five-year lifespan, Gaia will observe each of a billion stars about 70 times.

The unique mission is reliant on the work of Cambridge researchers who collect the vast quantities of data transmitted by Gaia to a data processing centre at the University, overseen by a team at the Institute of Astronomy.

“Gaia’s first major data release is both a wonderful achievement in its own right, and a taster of the truly dramatic advances to come in future years,” said Professor Gerry Gilmore from the Institute of Astronomy, who is also the UK Principal Investigator for Gaia. “Several UK teams have leading roles in Gaia’s Data Processing and Analysis efforts, which convert the huge raw data streams from the satellite into the beautiful science-ready information now made available for the global scientific and public communities. UK industry made critical contributions to the Gaia spacecraft. The UK public, including school students, as well as scientists, are sharing the excitement of this first ever galactic census.”

In addition to the work taking place at Cambridge, teams from Edinburgh, the Mullard Space Science Laboratory (MSSL) at UCL London, Leicester, Bristol and the Science and Technology Facilities Council’s Rutherford Appleton Lab are all contributing to the processing of the vast amounts of data from Gaia, in collaboration with industrial and academic partners from across Europe.

The team in Cambridge, led by Dr Floor van Leeuwen, Dr Dafydd Wyn Evans and Dr Francesca De Angeli, processed the flux information – the amount of energy that crosses a unit area per unit time – providing the calibrated magnitudes of around 1.6 billion stars, 1.1 billion of which are now published as part of the first data release.

The Cambridge team also check the daily photometric data for unexpected large outliers, which led to the regular publication of photometric science alerts that were ready for immediate follow-up observations from the ground.

“The sheer volume of data processed for this first release is beyond imagination: around 120 billion images were analysed, and most of these more than once, as all the processing is iterative,” said van Leeuwen, who is Gaia photometric data processing lead. “Many problems had to be overcome, and a few small ones still remain. Calibrations have not yet reached their full potential. Nevertheless, we are already reaching accuracies that are significantly better than expected before the mission, and which can challenge most ground-based photometric data in accuracy.”

“This first Gaia data release has been an important exercise for the Gaia data reduction teams, getting them to focus on deliverable products and their description,” said Evans. “But it is only the first small step towards much more substantial results.”

While today marks the first major data release from Gaia, in the two years since its launch, the satellite has been producing scientific results in the form of Gaia Alerts.

Dr Simon Hodgkin, lead of the Cambridge Alerts team said, “The Gaia Alerts project takes advantage of the fact that the Gaia satellite scans each part of the sky repeatedly throughout the mission. By comparing successive observations of the same patch of sky, scientists can search for transients – astronomical objects which brighten, fade, change or move. These transients are then announced to the world each day as Gaia Alerts for both professional and amateur astronomers to observe with telescopes from the ground.”

The range of Gaia’s discoveries from Science Alerts is large – supernovae of various types, cataclysmic variable stars, novae, flaring stars, gravitational microlensing events, active galactic nuclei and quasars, and many sources whose nature remains a mystery.

Gaia has discovered many supernovae, the brilliant explosions of stars at the end of their lives. Many of these have been ‘Type Ia’ supernovae, which can be used to measure the accelerating expansion of the Universe. But among these apparently typical supernovae there have been some rarer events. Gaia16ada was spotted by Gaia in the nearby galaxy NGC4559, and appears to be an eruption of a very massive, unstable star. The Hubble Space Telescope observed this galaxy some years ago, allowing astronomers to pinpoint the precise star which erupted.

Another lucky catch for Gaia was the discovery of Gaia16apd – a supernova which is nearly a hundred times brighter than normal. Astronomers still don’t know what the missing ingredient in these ultra-bright supernovae is, and candidates include exotic rapidly spinning neutron stars, or jets from a black hole. Cambridge astronomer Dr Morgan Fraser is trying to understand these events, saying, “We have only found a handful of these exceptionally bright supernovae, compared to thousands of normal supernovae. For Gaia to spot one so nearby is a fantastic result.”

Many of the Gaia Alerts found so far are bright enough to be observable with a small telescope. Amateur astronomers have taken images of supernovae found by Gaia, while schoolchildren have used robotic telescopes including the Faulkes Telescopes in Australia and Hawaii to do real science with transients.

Dr Hodgkin said: “Since the announcement of the first transients discovered with Gaia in September 2014, over one thousand alerts have been released. With Gaia continually relaying new observations to ground, and our team working on finding transients continually improving their software, the discoveries look set to continue well into the future!”

For the UK teams the future means providing improvements in the pre-processing of the data and extending the processing to cover the photometric Blue and Red prism data. Also data from the Radial Velocity Spectrometer, with major involvement from MSSL, will be included in future releases. The photometric science alerts will continue to operate throughout the mission, and summaries of the results will be included in future releases. “Despite the considerable amount of data, the first Gaia data release provides just a taste of the accuracy and completeness of the final catalogue,” said De Angeli.

The Cambridge Gaia team has also released a dedicated smartphone app, which will allow anyone worldwide to follow the Gaia Alerts discoveries as they happen. Real spacecraft data will be available to the world as soon as it is processed, with users able to follow the discoveries and see what they are. Information to access the app is available athttps://gaia.ac.uk.

The Gaia data processing teams in the UK have been and are being supported by the UK Space Agency and the STFC. STFC helped the set-up of the data applications centre and STFC’s current support involves the UK exploitation of the scientific data to be yielded from the mission. Industrial partners include Airbus, MSSL and e2v Technologies.

Traumatic brain injury is a serious injury to the brain, often caused by road traffic accidents, assaults or falls. It can lead to dangerous swelling in the brain which, in turn, can lead to brain damage or even death.

A team led by researchers at the Department of Clinical Neurosciences, University of Cambridge, and based at Addenbrooke’s Hospital, recruited over 400 traumatic brain injury patients over a ten-year period from the UK and another 19 countries worldwide. They then randomly assigned the patients to one of two groups for treatment – craniectomy or medical management.

In research published this week in the New England Journal of Medicine, the researchers report that six months after the head injury, just over one in four patients (27%) who received a craniectomy had died compared to just under a half (49%) of patients who received medical management. However, the picture was complicated as patients who survived after a craniectomy were more likely to be dependent on others for care (30.4% compared to 16.5%).

Further follow-up showed that patients who survived following a craniectomy continued improving from six to 12 months after injury. As a result, at 12 months, nearly half of craniectomy patients were at least independent at home (45.4%), as compared with one-third of patients in the medical group (32.4%).

Peter Hutchinson, Professor of Neurosurgery at the Department of Clinical Neurosciences at Cambridge, says: “Traumatic brain injury is an incredibly serious and life-threatening condition. From our study, we estimate that craniectomies can almost halve the risk of death for patients with a severe traumatic brain injury and significant swelling. Importantly, this is the first high-quality clinical trial in severe head injury to show a major difference in outcome. However, we need to be really conscious of the quality of life of patients following this operation which ranged from vegetative state through varying states of disability to good recovery.”

Angelos Kolias, Clinical Lecturer at the Department, adds: “Doctors and families will need to be aware of the wide range of possible long-term outcomes when faced with the difficult decision as to whether to subject someone to what is a major operation. Our next step is to look in more detail at factors that predict outcome and at ways to reduce any potential adverse effects following surgery. We are planning to hold a consensus meeting in Cambridge next year to discuss these issues.”

The research was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership, with further support from the NIHR Cambridge Biomedical Research Centre, the Academy of Medical Sciences, the Health Foundation, the Royal College of Surgeons of England and the Evelyn Trust.

Reference

Hutchinson, PJ et al. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension, NEJM; 2 Sept 2016

Researchers have detected two massive holes which have been ‘punched’ through a stream of stars just outside the Milky Way, and found that they were likely caused by clumps of dark matter, the invisible substance which holds galaxies together and makes up a quarter of all matter and energy in the universe.

The scientists, from the University of Cambridge, found the holes by studying the distribution of stars in the Milky Way. While the clumps of dark matter that likely made the holes are gigantic in comparison to our Solar System – with a mass between one million and 100 million times that of the Sun – they are actually the tiniest clumps of dark matter detected to date.

The results, which have been submitted to the Monthly Notices of the Royal Astronomical Society, could help researchers understand the properties of dark matter, by inferring what type of particle this mysterious substance could be made of. According to their calculations and simulations, dark matter is likely made up of particles more massive and more sluggish than previously thought, although such a particle has yet to be discovered.

“While we do not yet understand what dark matter is formed of, we know that it is everywhere,” said Dr Denis Erkal from Cambridge’s Institute of Astronomy, the paper’s lead author. “It permeates the universe and acts as scaffolding around which astrophysical objects made of ordinary matter – such as galaxies – are assembled.”

Current theory on how the universe was formed predicts that many of these dark matter building blocks have been left unused, and there are possibly tens of thousands of small clumps of dark matter swarming in and around the Milky Way. These small clumps, known as dark matter sub-haloes, are completely dark, and don’t contain any stars, gas or dust.

Dark matter cannot be directly measured, and so its existence is usually inferred by the gravitational pull it exerts on other objects, such as by observing the movement of stars in a galaxy. But since sub-haloes don’t contain any ordinary matter, researchers need to develop alternative techniques in order to observe them.

The technique the Cambridge researchers developed was to essentially look for giant holes punched through a stream of stars. These streams are the remnants of small satellites, either dwarf galaxies or globular clusters, which were once in orbit around our own galaxy, but the strong tidal forces of the Milky Way have torn them apart. The remnants of these former satellites are often stretched out into long and narrow tails of stars, known as stellar streams.

“Stellar streams are actually simple and fragile structures,” said co-author Dr Sergey Koposov. “The stars in a stellar stream closely follow one another since their orbits all started from the same place. But they don’t actually feel each other’s presence, and so the apparent coherence of the stream can be fractured if a massive body passes nearby. If a dark matter sub-halo passes through a stellar stream, the result will be a gap in the stream which is proportional to the mass of the body that created it.”

The researchers used data from the stellar streams in the Palomar 5 globular cluster to look for evidence of a sub-halo fly-by. Using a new modelling technique, they were able to observe the stream with greater precision than ever before. What they found was a pair of wrinkled tidal tails, with two gaps of different widths.

By running thousands of computer simulations, the researchers determined that the gaps were consistent with a fly-by of a dark matter sub-halo. If confirmed, these would be the smallest dark matter clumps detected to date.

“If dark matter can exist in clumps smaller than the smallest dwarf galaxy, then it also tells us something about the nature of the particles which dark matter is made of – namely that it must be made of very massive particles,” said co-author Dr Vasily Belokurov. “This would be a breakthrough in our understanding of dark matter.”

The reason that researchers can make this connection is that the mass of the smallest clump of dark matter is closely linked to the mass of the yet unknown particle that dark matter is composed of. More precisely, the smaller the clumps of dark matter, the higher the mass of the particle.

Since we do not yet know what dark matter is made of, the simplest way to characterise the particles is to assign them a particular energy or mass. If the particles are very light, then they can move and disperse into very large clumps. But if the particles are very massive, then they can’t move very fast, causing them to condense – in the first instance – into very small clumps.

“Mass is related to how fast these particles can move, and how fast they can move tells you about their size,” said Belokurov. “So that’s why it’s so interesting to detect very small clumps of dark matter, because it tells you that the dark matter particle itself must be very massive.”

“If our technique works as predicted, in the near future we will be able to use it to discover even smaller clumps of dark matter,” said Erkal. “It’s like putting dark matter goggles on and seeing thousands of dark clumps each more massive than a million suns whizzing around.”

Reference:
Denis Erkal et al. ‘A sharper view of Pal 5’s tails: Discovery of stream perturbations with a novel non-parametric technique.’ arXiv:1609.01282

The findings, published in Nature Genetics on Monday, could help find drugs that target specific weaknesses in each subtype of the disease, potentially making treatment more effective and boosting survival.

Researchers looked at the complete genetic make-up of 129 oesophageal cancers and were able to subdivide the disease into three distinct types based on patterns detected in the DNA of the cancer cells called signatures.

The first subtype they found had faults in their DNA repair pathways. Damage to this pathway is known to increase the risk of breast, ovarian and prostate cancers. Patients with this subtype may benefit from a new family of drugs called PARP inhibitors that kill cancer cells by exploiting this weakness in their ability to repair DNA.

The second subtype had a higher number of DNA mistakes and more immune cells in the tumours, which suggests these patients could benefit from immunotherapy drugs already showing great promise in a number of cancer types such as skin cancer.

The final subtype had a DNA signature that is mainly associated with the cell ageing process and means this group might benefit from drugs targeting proteins on the surface of the cancer cells which make cells divide.

Professor Rebecca Fitzgerald, lead researcher based at the MRC Cancer Unit at the University of Cambridge, said: “Our study suggests we could make changes to the way we treat oesophageal cancer.

“Targeted treatments for the disease have so far not been successful, and this is mostly down to the lack of ways to determine which patients might benefit from different treatments. These new findings give us a greater understanding of the DNA signatures that underpin different subtypes of the disease and means we could better tailor treatment.

“The next step is to test this approach in a clinical trial. The trial would use a DNA test to categorise patients into one of the three groups to determine the best treatments for each group and move away from a one-size-fits-all approach.”

Each year around 8,800 people are diagnosed with oesophageal cancer in the UK, with just 12 per cent surviving for at least ten years. Cancer Research UK, who along with the Medical Research Council funded the study, has prioritised research into oesophageal cancer to help more people survive the disease by bringing people together, building infrastructure and developing the next generation of research leaders.

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Being able to distinguish distinct types of oesophageal cancer is a genuinely new discovery from this work.  For the first time we may be able to identify and test targeted treatments designed to exploit the cancer’s specific weaknesses. Although survival rates from oesophageal cancer have been slowly rising in the last few years they are still far too low, and this research points the way to a completely new way of understanding and tackling the disease.”

The study, funded by Cancer Research UK and the Medical Research Council, is part of the Cancer Research UK-funded International Cancer Genome Consortium.

Reference

Secrier, M. et al. Mutational signatures in esophageal adenocarcinoma reveal etiologically distinct subgroups with therapeutic relevance Nature Genetics, 2016.

Estimates suggest that among children who try smoking, between one third and one half are likely to become regular smokers within two to three years. However, young people are now more likely to experiment with e-cigarettes than they are with tobacco cigarettes. For example, a 2014 study found that 22% of children aged 11-15 in England had experimented with e-cigarettes, compared to 18% for tobacco cigarettes.

There is concern that the increasing exposure of children to e-cigarette adverts could be contributing to high rates of experimentation; in the US, adolescents’ exposure to e-cigarette adverts on TV more than trebled between 2011 to 2013. E-cigarette brands often market themselves as helping people quit smoking and as healthier and cheaper alternatives to tobacco cigarettes.

In this study from researchers at the Behaviour and Health Research Unit, University of Cambridge, and the University of North Carolina Gillings School of Global Public Health, and published today in the journal Tobacco Control, more than 400 English children aged 11-16 who had never smoked or ‘vaped’ previously were recruited and randomly allocated to one of three groups. One group was shown ten adverts that depicted e-cigarettes as glamorous, a second group was shown ten adverts that portrayed them as healthy, and a third control group was shown no adverts.

The children were then asked a series of questions aimed at determining their attitudes towards smoking and vaping. Children shown the adverts were no more or less likely than the control group to perceive tobacco smoking as appealing and all three groups understood that smoking more than ten cigarettes a day was harmful. However, both groups of children exposed to the e-cigarette adverts, both healthy and glamorous, were less likely to believe that smoking one or two tobacco cigarettes occasionally was harmful.

Dr Milica Vasiljevic from the Department of Public Health and Primary Care at the University of Cambridge says: “While we can be optimistic that the adverts don’t seem to make tobacco smoking more appealing to young people, they do appear to make occasional smoking seem less harmful. This is worrying, as we know that even occasional tobacco smoking is bad for your health, and young people who smoke occasionally believe they are somehow immune to its effects and do not feel the need to quit.”

The group of children that were shown adverts depicting e-cigarettes as glamorous also believed e-cigarette vaping to be more prevalent than did the other two groups.

Professor Theresa Marteau, Director of the Behaviour and Health Research Unit and a Fellow of Christ’s College, University of Cambridge, adds: “E-cigarette marketing across Europe is regulated under the new EU Tobacco Products Directive, which came into effect on the 20th May this year. The Directive limits the exposure of children to TV and newspaper e-cigarette adverts. However, it does not cover advertising in the form of posters, leaflets, and adverts at point of sale, nor does it cover the content of marketing materials depicting e-cigarettes as glamorous or healthy. The findings from our study suggest these omissions could present a threat to the health of children.”

The study was funded by the Department of Health.

Reference
Petrescu, D, Vasiljevic, M, Pepper, JK, Ribisl, KM, Marteau, TM . What is the impact of e-cigarette adverts on children’s perceptions of tobacco smoking? An experimental study. Tobacco Control; 6 Sept 2016; DOI: 10.1136/tobaccocontrol-2016-052940

Type 1 diabetes is one of the most common chronic diseases in children; around one in 4,000 children under 14 years of age is diagnosed with the disease each year in the UK. The disease causes the pancreas to stop producing sufficient insulin to regulate blood sugar (glucose) levels, and poor glucose control can lead to complications including eye, heart and kidney disease. Episodes of very low glucose levels can cause serious complications and may be life threatening.

People affected by the condition have to manage their condition through long term treatment. This usually involves regular insulin injections – in some cases, several times a day. However, a team at the University of Cambridge and Cambridge University Hospitals hopes to replace these treatments with an artificial pancreas, a small, portable medical device designed to carry out the function of a healthy pancreas in controlling blood glucose levels, using digital technology to automate insulin delivery. The system is worn externally on the body, and is made up of three functional components: continuous glucose monitoring, a computer algorithm to calculate the insulin dose, and an insulin pump.

The artificial pancreas promises to transform management of type 1 diabetes. Several trials have already shown that it is effective for use both school children and adults in the home environment, and last year saw the first natural birth to a mother fitted with an artificial pancreas. However, there has as yet been no research into its use by young children at home.

Now, KidsAP, a collaboration led the University of Cambridge and involving institutes across Europe and in the US, has received a €4.6millon under the European Commission’s Horizon 2020 programme to carry out a trial of the artificial pancreas among children aged one to seven years with type 1 diabetes. Cambridge has received a €1.6m share of the grant to act as coordinator of the project.

“We’ve already seen that the artificial pancreas can have a very positive effect on people’s lives and now, thanks to funding from the European Commission, we can see whether young children will also see these same benefits,” said Dr Roman Hovorka from the Department of Paediatrics at the University of Cambridge and Addenbrooke’s Hospital, who is leading the project. “At the moment, children have to have frequent insulin injections that are at best inconvenient, but at worst painful. We hope this new technology will eliminate this need.”

An initial pilot of 24 children, the main study will split 94 children into two groups: one will be treated over a year by the artificial pancreas and the other half by state-of-the-art insulin pump therapy, already used by some adults and teenagers. The researchers will measure quality of life and investigate the impact of the two approaches on the children’s daily life, as well as looking at which is the more effective, and cost-effective, approach.

“If the artificial pancreas is shown to be more beneficial than insulin pump therapy, then we expect that it will change how type 1 diabetes is managed both nationally and internationally, with a much improved quality of life for young children,” added Professor David Dunger, collaborator on the project.

With funding from The Kavli Foundation, the think tank will bring together some of the major researchers in exoplanetary science – arguably the most exciting field in modern astronomy – for a series of annual meetings to address the biggest questions in this field which humanity could conceivably answer in the next decade.

“We’re really at the frontier in exoplanet research,” said Dr Nikku Madhusudhan of Cambridge’s Institute of Astronomy, who is leading the think tank. “The pace of new discoveries is incredible – it really feels like anything can be discovered any moment in our exploration of extra-terrestrial worlds. By bringing together some of the best minds in this field we aim to consolidate our collective wisdom and address the biggest questions in this field that humanity can ask and answer at this time.”

Tremendous advances have been made in the study of exoplanets since the first such planet was discovered around a sun-like star in 1995 by the Cavendish Laboratory’s Professor Didier Queloz. Just last month, a potentially habitable world was discovered in our own neighbourhood, orbiting Proxima Centauri, the nearest star to the sun.

However, there are still plenty questions to be answered, such as whether we’re capable of detecting signatures of life on other planets within the next ten years, what the best strategies are to find habitable planets, how diverse are planets and their atmospheres, and how planets form in the first place.

With at least four space missions and numerous large ground-based facilities scheduled to become operational in the next decade, exoplanetary scientists will be able to detect more and more exoplanets, and will also have the ability to conduct detailed studies of their atmospheres, interiors, and formation conditions. At the same time, major developments are expected in all aspects of exoplanetary theory and data interpretation.

In order to make these major advances in the field, new interdisciplinary approaches are required. Additionally, as new scientific questions and areas emerge at an increasingly fast pace, there is a need for a focused forum where emerging questions in frontier areas of the field can be discussed. “Given the exciting advancements in exoplanetary science now is the right time to assess the state of the field and the scientific challenges and opportunities on the horizon,” said Professor Andy Fabian, director of the Institute of Astronomy at Cambridge.

The think tank will operate in the form of a yearly Exoplanet Symposium series which will be focused on addressing pressing questions in exoplanetary science. One emerging area or theme in exoplanetary science will be chosen each year based on its critical importance to the advancement of the field, relevance to existing or imminent observational facilities, need for an interdisciplinary approach, and/or scope for fundamental breakthroughs.

About 30 experts in the field from around the world will discuss outstanding questions, new pathways, interdisciplinary synergies, and strategic actions that could benefit the exoplanet research community.

The inaugural symposium, “Kavli ExoFrontiers 2016”, is being held this week in Cambridge. The goal of this first symposium is to bring together experts from different areas of exoplanetary science to share their visions about the most pressing questions and future outlook of their respective areas. These visions will help provide both a broad outlook of the field and identify the ten most important questions in the field that could be addressed within the next decade. “We hope the think tank will provide a platform for new breakthroughs in the field through interdisciplinary and international efforts while bringing the most important scientific questions of our time to the fore,” said Madhusudhan. “We are in the golden age of exoplanetary science.”

More information about the Kavli ExoFrontiers 2016 Symposium is available at: www.ast.cam.ac.uk/meetings/2016/kavli.exofrontiers.2016.symposium

Many of the major new outbreaks of disease, particularly in Africa, are so-called zoonotic infections, diseases that are transmitted to humans from animals. The Ebola virus, for example, which recently killed over 11,000 people across Africa, was most likely transmitted to humans from fruit bats.

Modelling how outbreaks arise and whether they will take hold or quickly die out has proved challenging, with two factors in particular being difficult to quantify. The first is ‘spillover’, where the pathogen – a virus or parasite, for example – passes from an animal to a person. This can be through direct transmission, for example by being bitten or by eating ‘bush meat’ (wild animals such as fruit bats or monkeys that are caught and consumed), or indirectly, such as through contact with faeces or disease-carrying mosquitoes.

In many cases, a spillover will go no further. When a human is bitten by a rabid dog, they may become infected, but as the disease cannot transmit from human-to-human, the disease hits a dead end.

However, in some cases the infected person goes on to infect other humans. This is the case for diseases such as Ebola, Lassa fever (spread from rodents) and Crimean Congo haemorrhagic fever (spread from ticks). But in many cases, unless there are additional spillover events, the disease eventually fades out. This is referred to as a ‘stuttering chain’, and even though the disease is transmitted from human-to-human, they are still considered to be zoonotic infections.

Diseases such as HIV, however, which almost certainly began as a spillover from chimpanzees, are no longer considered to be zoonotic as the chain of transmission from humans to other humans is continuous and no longer relies on spillover to sustain transmission.

“Modelling spillovers is a real challenge,” says Dr Gianni Lo Iacono from the Department of Veterinary Medicine at the University of Cambridge. “We don’t have particularly good data on wildlife numbers, such as fruit bats in Sierra Leone, and only a crude idea of their geographic distribution and how many are infected. Even in the UK, we don’t really know how many deer we have, which would be really useful to estimate the risk of Lyme disease.”

In addition, measuring the likelihood of contact with the infected animals is also extremely difficult as it involves understanding human and animal behaviour.

Stuttering transmission, too, can be difficult to model, says Dr Lo Iacono. “In the case of Lassa fever, people who catch the disease from animals show the same symptoms as those who get it from humans. So is this case a spillover or part of a human-to-human chain of transmission? And if members of the same family get the disease, have they caught it from a family member or from the same pot of contaminated rice?

“Sometimes you can be lucky and work this out, as we did in a previous study, but this was possible because information of outbreaks that were known to be pure human-to-human chains was, unusually, available. But we need more general methods.”

Dr Lo Iacono and colleagues have developed the most coherent and potentially most accurate mathematical model to date for zoonotic diseases, which incorporates spillover and stuttering transmission.

“The pathogen does not care if it jumped from an animal or from another human; the only difference is that in a stuttering transmission an infected person can trigger other chains of human infections. A general, realistic model should capture this mechanism,” adds Dr Lo Iacono.

Details of the model, including a demonstration applying the framework to Lassa fever, are published today in the open access journal PLOS Neglected Tropical Diseases.

“By modelling potential outbreaks more accurately, we can help inform public health messages,” explains Professor James Wood, Head of the Department of Veterinary Medicine, and senior author. “If you know that most cases of an outbreak of Lassa fever come from spillovers, then the message might be ‘kill the rats’, but if it is now mainly spreading between humans, the messages will be around washing your hands or avoiding contact with bodily fluids.”

The beauty of the model, say the researchers, is that it is simple to implement, so public health officials and non-mathematicians could easily use it. It also allows for the incorporation of data from different disciplines, factoring in socioeconomic, ecological and environmental factors, for example.

“It’s important to understand if and how these other important factors can increase the impact of stuttering chains,” says Professor Wood. “Ebola has always been a very severe disease but previously confined to small, remote regions. Then suddenly, in the last two years it exploded in West Africa. Why? Was it because social patterns changed? Our model could be used to address such questions better.”

The research informing the paper was carried out as part of the Dynamic Drivers of Disease in Africa Consortium, which was funded by Ecosystem Services for Poverty Alleviation (ESPA).

Reference
Lo Iacono, G et al. A unified framework for the infection dynamics of zoonotic spillover and spread. PLOS NTD; 2 Sept 2016; DOI: 10.1371/journal.pntd.0004957

Mole rats, including the naked mole rat, live in underground colonies. The majority of rodents in the colonies are ‘workers’, with only one female (the ‘queen’) and one male responsible for breeding. All individuals cooperate by digging large underground tunnel systems to forage for food, and if a large food source is found, it is shared with the entire colony. ‘Queens’ and reproductive males remain in this role for their entire life after they have achieved this position. When a ‘queen’ dies, the strongest and largest helper is probably the prime candidate for inheriting the breeding position.

Early studies suggested that non-reproducing mole rats can be divided into non-workers, infrequent workers and frequent workers, and that most individuals stay members of distinct castes for their entire lives. Individual mole rats would focus on a particular task, such as digging, nest building or colony defence, throughout their lives.

Now, however, in a study published in Proceedings of the National Academy of Sciences, researchers from the Department of Zoology at the University of Cambridge have shown that in Damaraland mole rats, the contributions of individuals to cooperative activities change with age and that individual differences in behaviour that appeared to be a consequence of differences in caste are, in fact, age-related changes in behaviour. Whether variation in behaviour between naked mole rats is also a consequence of similar age-related changes is not known – but this seems likely.

Dr Markus Zöttl, first author of the study, explains: “In some ants, aphids and termites, individuals are born into castes that fulfil certain roles, such as soldiers or workers. Initially, everyone thought that this was only found in social invertebrates, like ants and bees, but in the eighties, the discovery of the social behaviour of mole rats challenged this view. Social mole rats were thought to be unique among vertebrates, in that they also had castes. To understand this fully, what we needed was long-term data on many mole rats over extended periods of their lives.”

To study mole rat development in more detail, a team at Cambridge led by Professor Tim Clutton-Brock from the Department of Zoology built a laboratory in the Kalahari Desert, where Damaraland mole rats are native, and established multiple colonies of mole rats in artificial tunnel systems. Over three years, they followed the lives of several hundred individuals to document how the behaviour of individuals changes as they age. All individuals were weighed and observed regularly to document their behavioural changes.

The researchers found that individual mole rats play different roles as they grow and get older.  Rather than being specialists, mole rats are generalists that participate in more or fewer community duties at different stages of their lives. Instead of behaving like ants or termites, where individuals are members of a caste and specialise in doing certain activities, all mole rats are involved in a range of different activities, and their contributions to cooperative activities increases with age.

“As Damaraland mole rats do not have castes, this may mean that castes are only found in social invertebrates and have not evolved in any vertebrates,” adds Dr Zöttl. “Mole rat social organisation probably has more in common with the societies of other cooperative mammals, such as meerkats and wild dogs, than with those of social insects.”

The research was funded by European Research Council.

In a new study, a team of academics at the Centre for Misfolding Diseases, in the Department of Chemistry at the University of Cambridge, show that tiny changes in the amino acid sequence of the protein alpha-synuclein can have a dramatic effect on microscopic processes leading to its aggregation that may occur in the brain, eventually resulting in someone being diagnosed with Parkinson’s Disease.

Alpha-synuclein is a protein made up of 140 amino acids, and under normal circumstances plays an important part in helping with the smooth flow of chemical signals in the brain.

Parkinson’s Disease is thought to arise because, for reasons researchers still do not fully understand, the same protein sometimes malfunctions. Instead of adopting the specific structural form needed to do its job, it misfolds and begins to cluster, creating toxic, thread-like structures known as amyloid fibrils. In the case of Parkinson’s Disease, these protein deposits are referred to as Lewy-bodies.

The new study examined mutated forms of alpha-synuclein which have been found in people from families with a history of Parkinson’s Disease. In all cases, these mutations involved just one change to the protein’s amino acid sequence.

Although the differences in the sequence are small, the researchers found that they can have a profound effect on how quickly or slowly fibrils start to form. They also found that the mutations strongly influence a process called “secondary nucleation”, in which new fibrils are formed, in an auto-catalytic manner, at the surface of existing ones and thus enable the disease to spread.

The study stresses that these findings do not explain why humans get the disease. Parkinson’s Disease does not always emerge as a result of the mutations and has multiple, complex causes, which are not fully understood.

Patrick Flagmeier, a PhD student at St John’s College, University of Cambridge, and the study’s lead author, said: “As a finding, it helps us to understand fundamental things about the system by which this disease emerges. In the end, if we can understand all of this better, that can help us to develop therapeutic strategies to confront it. Our hope is that this study will contribute to the global effort towards comprehending why people with these mutations get the disease more frequently, or at a younger age.”

Although people who do not have mutated forms of alpha-synuclein can still develop Parkinson’s Disease, the five mutations studied by the research team were already known as “familial” variants – meaning that they recur in families where the disease has emerged, and seem to increase the likelihood of its onset.

What was not clear, until now, is why they have this effect. “We wanted to know how these specific changes in the protein’s sequence influence its behaviour as it aggregates into fibrils,” Flagmeier said.

To understand this, the researchers conducted lab tests in which they added each of the five mutated forms of alpha-synuclein, as well as a standard version of the protein, to samples simulating the initiation of fibril formation, their growth and their proliferation.

The first round of tests examined the initiation of aggregation, using artificial samples recreating conditions in which misfolded alpha-synuclein attaches itself to small structures that are present inside brain cells called lipid vesicles, and then begins to cluster.

The researchers then tested how the different versions of the protein influence the ability of pre-formed fibrils to extend and grow. Finally, they tested the impact of mutated proteins on secondary nucleation, in which, under specific conditions, the fibrils can multiply and start to spread.

Overall, the tests revealed that while the mutated forms of alpha-synuclein do not notably influence the fibril growth, they do have a dramatic effect on both the initial formation of the fibrils, and their secondary nucleation. Some of the mutated forms of the protein made these processes considerably faster, while others made it almost “undetectably slow”, according to the researchers’ report.

“We have only recently discovered the autocatalytic amplification process of alpha-synuclein fibrils, and the results of the present study will help us to understand in much more detail the mechanism behind this process, and in what ways it differs from the initial formation of aggregates.” said Dr.  Alexander Buell, one of the senior authors on the study.

Why the mutations have this impact remains unclear, but the study opens the door to understanding this in detail by identifying, for the first time, that they have such a dramatic impact on very particular stages of the process.

Dr. Céline Galvagnion, another of the senior authors on the study, said: “This study quantitatively correlates individual changes in the amino acid sequence of alpha-synuclein with its tendency to aggregate. However, the effect of these mutations on other parameters such as the loss of the protein’s function and the efficiency of clearance of alpha-synuclein needs to be taken into account to fully understand the link between the familial mutations of alpha-synuclein and the onset of Parkinson’s Disease.”

“The effects we observed were changes of several orders of magnitude and it was unexpected to observe such dramatic effects from single-point mutations,” Flagmeier said. “It seems that these single-point mutations in the sequence of alpha-synuclein play an important role in influencing particular microscopic steps in the aggregation process that may lead to Parkinson’s Disease.”

The full study, which also involves Professors Chris Dobson and Tuomas Knowles, is published in the journal, Proceedings of the National Academy of Sciences.

Reference:

Flagmeier, P. et. al: Mutations associated with familial Parkinson’s disease alter the initiation and amplification steps of α-synuclein aggregation. PNAS (2016): DOI: 10.1073/pnas.1604645113

Astronomers have identified a young star, located almost 11,000 light years away, which could help us understand how the most massive stars in the Universe are formed. This young star, already more than 30 times the mass of our Sun, is still in the process of gathering material from its parent molecular cloud, and may be even more massive when it finally reaches adulthood.

The researchers, led by a team at the University of Cambridge, have identified a key stage in the birth of a very massive star, and found that these stars form in a similar way to much smaller stars like our Sun – from a rotating disc of gas and dust. The results will be presented this week at the Star Formation 2016 conference at the University of Exeter, and are reported in the Monthly Notices of the Royal Astronomical Society.

In our galaxy, massive young stars – those with a mass at least eight times greater than the Sun – are much more difficult to study than smaller stars. This is because they live fast and die young, making them rare among the 100 billion stars in the Milky Way, and on average, they are much further away.

“An average star like our Sun is formed over a few million years, whereas massive stars are formed orders of magnitude faster — around 100,000 years,” said Dr John Ilee from Cambridge’s Institute of Astronomy, the study’s lead author. “These massive stars also burn through their fuel much more quickly, so they have shorter overall lifespans, making them harder to catch when they are infants.”

The protostar that Ilee and his colleagues identified resides in an infrared dark cloud – a very cold and dense region of space which makes for an ideal stellar nursery. However, this rich star-forming region is difficult to observe using conventional telescopes, since the young stars are surrounded by a thick, opaque cloud of gas and dust. But by using the Submillimeter Array (SMA) in Hawaii and the Karl G Jansky Very Large Array (VLA) in New Mexico, both of which use relatively long wavelengths of light to observe the sky, the researchers were able to ‘see’ through the cloud and into the stellar nursery itself.

By measuring the amount of radiation emitted by cold dust near the star, and by using unique fingerprints of various different molecules in the gas, the researchers were able to determine the presence of a ‘Keplerian’ disc – one which rotates more quickly at its centre than at its edge.

“This type of rotation is also seen in the Solar System – the inner planets rotate around the Sun more quickly than the outer planets,” said Ilee. “It’s exciting to find such a disc around a massive young star, because it suggests that massive stars form in a similar way to lower mass stars, like our Sun.”

The initial phases of this work were part of an undergraduate summer research project at the University of St Andrews, funded by the Royal Astronomical Society (RAS). The undergraduate carrying out the work, Pooneh Nazari, said, “My project involved an initial exploration of the observations, and writing a piece of software to ‘weigh’ the central star. I’m very grateful to the RAS for providing me with funding for the summer project — I’d encourage anyone interested in academic research to try one!”

From these observations, the team measured the mass of the protostar to be over 30 times the mass of the Sun. In addition, the disc surrounding the young star was also calculated to be relatively massive, between two and three times the mass of our Sun. Dr Duncan Forgan, also from St Andrews and lead author of a companion paper, said, “Our theoretical calculations suggest that the disc could in fact be hiding even more mass under layers of gas and dust. The disc may even be so massive that it can break up under its own gravity, forming a series of less massive companion protostars.”

The next step for the researchers will be to observe the region with the Atacama Large Millimetre Array (ALMA), located in Chile. This powerful instrument will allow any potential companions to be seen, and allow researchers to learn more about this intriguing young heavyweight in our galaxy.

This work has been supported by a grant from the European Research Council.

References:
J.D. Ilee et al. ‘G11.92-0361 MM1: A Keplerian disc around a massive young proto O-star.’ Monthly Notices of the Royal Astronomical Society (2016): DOI: 10.1093/mnras/stw1912

D. H. Forgan et al. ‘Self-gravitating disc candidates around massive young stars.’ Monthly Notices of the Royal Astronomical Society (2016): DOI: 10.1093/mnras/stw1917