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Illustration of the brain

It might sound alarmingly similar to the prehistoric procedure of trepanning, but decompressive craniectomy – the removal of a large part of the skull to reduce swelling in the brain – is still used as a last-resort treatment for traumatic brain injury or stroke by surgeons around the world.

Perhaps unsurprisingly, the complication rate of this major operation is high. As the brain 'mushrooms' out of the skull following the removal of bone from the skull, stresses and stretches placed on other parts of the brain can lead to neuronal damage and potential long-term disability.

But this is no longer just a challenge for neurosurgeons. Mathematicians are now able to study and model the impact of surgery at organ level, developing a more specific picture across the whole brain. Professor Alain Goriely of Oxford Mathematics and Stanford colleagues Professor Ellen Kuhl and Dr Johannes Weickenmeier have looked at the issue by studying a standard physical problem: the problem of bulging in soft solids.

Bulging takes place when a material swells while constrained – except at an opening, as seen when the skull is opened during decompressive craniectomy and the brain bulges out of the newly created hole. This can create deformations in another part of the brain, away from the immediate incision.

Brain imagingResearchers used high-resolution magnetic resonance imaging to create craniectomy models.

Image credit: Alain Goriely

To quantify possible deformations inside the brain, the team created a personalised craniectomy model from high-resolution medical resonance imaging. Their study reveals three mechanisms of failure that could denote damage beyond the initial incision point: axonal stretch in the centre of the bulge (axons are nerve fibres that carry impulses away from nerve cells), axonal compression at the edge of the craniectomy, and axonal shear around the opening. Strikingly, even small amounts of swelling can induce axonal strain in excess of 30% above reported damage thresholds in patients.

Professor Goriely said: 'This research points towards a possible way of proving and identifying long-term damage to the brain following decompressive craniectomy. Indeed, this theoretical study is a first step towards gaining better insight into the complex mechanisms underlying craniectomy and opens the door for systematic personalised studies of craniectomy in patients. The next step is to combine this theoretical work with experimental and clinical work to enable surgeons to provide better-informed and more successful treatments.'

Fish oil and aspirin

On World Alzheimer's Day (21 September), Oxford scientists are beginning a new study in the battle to beat the increasing issue of dementia.

Dementia is a truly global issue and to tackle it, we need a joined-up approach. Oxford is leading the way in dementia research and this funding will help us to continue to make progress for all those affected.

Professor Richard Wade-Martins, Coordinator, Oxford Alzheimer's Research UK Network Centre 

Charity Alzheimer's Research UK, the UK’s leading dementia research charity, have increased their support for Oxford dementia research with two awards. One will support the community of dementia researchers in Oxford to work together towards the goal of defeating dementia. The second award will allow a team to study whether taking aspirin and omega-3 fish oils can improve people's memory and thinking skills.

Dementia is one of the greatest challenges facing modern medicine and there are currently 850,000 people in the UK living with dementia. For example, Oxfordshire alone has more than 8,000 people with dementia.

In the first ever project awarded by Alzheimer's Research UK's Global Clinical Trials Fund, Professor Jane Armitage at the University of Oxford will study whether aspirin or omega-3 fish oils have an effect on memory and thinking skills in people with diabetes. As an add-on to an existing clinical trial called ASCEND, funded by the British Heart Foundation, Prof Armitage and her team will test the memory and thinking skills in around 10,000 people who have taken aspirin, omega-3 fish oils or a placebo for 6.5 years.

Having poor heart health is associated with an increased risk of dementia, and diabetes is a risk factor for both heart health and dementia. Both aspirin and omega-3 fish oils are thought to reduce complications resulting from poor heart health, such as heart attacks and stroke, but previous studies looking at their effects on memory and thinking have been too small to detect what may be small but worthwhile benefits.

We are beginning to unravel the links between cardiovascular health, diabetes and dementia, and this trial will provide important insight into this relationship.

Professor Jane Armitage, Nuffield Department of Population Health

Prof Jane Armitage explains: 'We are beginning to unravel the links between cardiovascular health, diabetes and dementia, and this trial will provide important insight into this relationship. This is an excellent opportunity to study an existing group of around 10,000 people who have been taking aspirin or omega-3 fish oils for 6.5 years and examine the effects on their memory and thinking skills. Although these drugs are not being investigated for their potential to treat dementia, if they are found to reduce the risk of developing the condition then this could be of significant benefit in supporting healthy ageing.'

Oxford is home to the Alzheimer's Research UK Oxford Research Network Centre. The charity’s Research Network is the largest community of dementia researchers in the UK, with over 1,000 members across 15 virtual Research Centres. Being part of the Network provides researchers with unique access to funding for small grants to support travel, equipment and networking.

Prof Richard Wade-Martins, Coordinator of the Oxford Network Centre, welcomed the new funding. He said: 'We are delighted that Alzheimer's Research UK has continued to support pioneering research in the city. Being part of a UK-wide Network of dementia researchers is a real boost to us, enabling us to collaborate with other scientists and explore new avenues of research. Dementia is a truly global issue and to tackle it, we need a joined-up approach. Oxford is leading the way in dementia research and this funding will help us to continue to make progress for all those affected.'

Dr Rosa Sancho, Head of Research at Alzheimer's Research UK, said: 'We are dedicated to funding the best minds and forging the most effective partnerships, and so are very glad to be supporting the vital work of scientists in Oxford. There is currently no way to prevent dementia, and so research into the factors that affect a person’s risk of the condition is crucial if we are to help people achieve a better quality of life for longer. Dr Armitage has a wealth of experience of clinical trials relating to diabetes and cardiovascular disease, and it’s fantastic that she is now applying her skills to addressing important questions in dementia research.

'We know that we will not defeat dementia in isolation, which is why initiatives such as the Research Network are crucial to support researchers at a grass-roots level. Sharing of ideas and resources will spur scientists on to think more ambitiously and help us progress faster towards our goal.'

Cecil the lion

A little over a year ago, Professor David Macdonald of Oxford University's Wildlife Conservation Research Unit (WildCRU) spoke of his desire to harness the global interest in the killing of Cecil the lion, creating a movement rather than simply a moment.

That journey continues this week with the Cecil Summit, a workshop held in Oxford that will bring together leading figures from across the world to consider future initiatives to preserve the African lion.

The summit will culminate in a free public event on Wednesday 7 September at the Blavatnik School of Government in which anyone interested in conservation will be able to hear the thoughts of top lion experts, as well as a variety of innovative thinkers from fields as diverse as economics, development, international relations and ethics.

The discussion, to be introduced with an illustrated talk by Professor Macdonald, will be chaired by Alan Rusbridger, Principal of Lady Margaret Hall, Oxford and former editor of The Guardian. It will take place from 5pm to 7pm. The summit follows more than a year of sustained interest in the story of Cecil, who was killed by a big game hunter outside Hwange National Park, Zimbabwe on 2 July 2015. Researchers from WildCRU were studying and tracking Cecil and his pride as part of their lion conservation research.

Professor Macdonald, the founding Director of WildCRU, explained the context for the summit: 'Lions, arguably the most iconic species in the world, are doing badly. That understatement captures the shocking fact that wild lions nowadays roam in only 8% of their historic range. Last year, researchers from WildCRU and Panthera, the big cat charity based in New York, published the finding that whereas a hundred years ago it is widely thought there were about 200,000 lions, today there are closer to 20,000.

'Against this distressing but widely ignored background, suddenly everything changed with the killing of Cecil, a fascinating elderly male Zimbabwean lion that WildCRU had been satellite tracking since 2008. Cecil's death prompted unprecedented media interest globally, and so with the world's attention focused on lions, WildCRU and Panthera resolved to hold the Cecil Summit with the purpose of asking whether the morbid trajectory of the lion's fate could be reversed, breaking the mould of conservation by seeking new, innovative approaches from beyond the realms of dedicated field biologists.'

The summit is a joint venture between Oxford and Panthera, whose President Luke Hunter said: 'The tragedy of Cecil's death spurred a unique sea change moment for global awareness of the lion's precarious state. But over a year later, the species is still in freefall in many places. The lion is running out of time.

'We hope that the Cecil Summit's brain trust of conservationists and innovators can spur a new infusion of support for African governments and people working to save the magnificent African lion.'

Speaking from WildCRU's centre at Tubney House near Oxford, Professor Macdonald said: 'In my experience, this summit is unique: we take 30 innovative minds, present them with a new problem, mix them with some conservation specialists, shake and stir, and hope for a breakthrough. It may work, it may not, but at least we will have tried. We'll have grasped the unique Cecil moment and challenged ourselves to find a new way ahead for the Cecil movement.

'Perhaps the unique feature of our approach, forcing inter-disciplinarity between those who know about lions and those who know about delivering high-level change to the human enterprise, will itself become a way ahead in conservation: the Tubney Format!'

He added: 'We believe that the more brains are involved the better, which is why we've arranged a public session in which Alan Rusbridger will lead a conversation with such guests as Rory Stewart, the UK's Minister for International Development; Achim Steiner, Director of the Oxford Martin School and recently head of the United Nations Environment Programme; Wilson Mutinhima, the Director General of Zimbabwe's National Parks; Craig Packer, the world's leading lion biologist; and Tom Kaplan, WildCRU's patron and the greatest benefactor in history to big cat conservation.'

The Cecil Summit's public event will take place at the Blavatnik School of Government from 5pm UK time on Wednesday 7 September. Attendance is free, but booking is required via the Oxford University website. The event will also be live-streamed on WildCRU's YouTube channel.

Drugs

It probably isn't surprising to read that pharmaceutical drugs don't always do what they're supposed to. Adverse side effects are a well-known phenomenon and something many of us will have experienced when taking medicines.

Sometimes, these side effects can be caused when a drug hits the wrong target, binding to the wrong protein. However, the difficulty of tracking this process means that little research has been carried out.

Now, a new study led by scientists at the University of Oxford and published in Nature Chemistry has shown how a series of anti-HIV protein inhibitor drugs can interfere with the processing of a protein known as prelamin A, essential for maintaining the shape of human cells and directly related to ageing.

The researchers used mass spectrometry – a long-established way of identifying molecules by measuring their mass – to observe directly the drugs' 'hitchhiking' on the wrong protein.

Professor Dame Carol Robinson of Oxford's Department of Chemistry, corresponding author on the paper, said: 'The "hitchhiking" of drugs on incorrect targets is a common problem but isn't much studied, as it can be difficult to observe directly. You have to know which proteins to look for, and only then can you target these proteins for further research.

'The results of this study surprised us, as the drugs target HIV proteases and were not thought to bind the human metalloprotease that is involved in processing prelamin A.'

The researchers found that the anti-HIV drugs lopinavir, ritonavir and amprenavir each blocked the processing of prelamin A.

Professor Robinson added: 'The association between some anti-HIV drugs and premature ageing has been suspected for some time through observation of patients undergoing treatment, but it hasn't been proved at the molecular level. There have also been other highly publicised drugs with off-target protein side effects, including an anti-diabetes drug that caused heart attacks in some patients.

'Now that we have developed this mass spectrometry-based approach, we anticipate that it will have widespread application, since it is likely that many drugs that are designed with a specific target in mind end up hitchhiking on other protein targets. It could even be used during the drug development process to determine if drugs are binding to the wrong targets at the molecular level.'

red dwarf

Why are we now?

Stuart Gillespie | 23 Aug 2016

We know that the universe is roughly 14 billion years old, and that someday it is likely to end – perhaps because of a Big Freeze, Big Rip or Big Crunch.

But what can we learn by considering our own place in the history of the universe? Why does life on Earth exist now, rather than at some point in the distant past or future?

A team of researchers including astrophysicists from the University of Oxford has set about trying to answer these questions – and their results raise the possibility that we Earthlings might be the first to arrive at the cosmic party.

The paper, led by Professor Avi Loeb of Harvard University and published in the Journal of Cosmology and Astroparticle Physics, suggests that life in the universe is much more likely in the future than it is now. That's partly because the necessary elements for life, such as carbon and oxygen, took tens of millions of years to develop following the Big Bang, and partly because the lower-mass stars best suited to hosting life can glow for trillions of years, giving ample time for life to evolve in the future.

Dr Rafael Alves Batista of Oxford's Department of Physics, one of the study's authors, says: 'The main result of our research is that life seems to be more likely in the future than it is now. That doesn't necessarily mean we are currently alone, and it is important to note that our numbers are relative: one civilisation now and 1,000 in the future is equivalent to 1,000 now and 1,000,000 in the future.

'Given this knowledge, the question is therefore why we find ourselves living now rather than in the future. Our results depend on the lifetime of stars, which in turn depend on their mass – the larger the star, the shorter its lifespan.'

In order to arrive at the probability of finding a habitable planet, the team came up with a master equation involving the number of habitable planets around stars, the number of stars in the universe at a given time (including their lifespan and birth rate, and the typical mass of newly born stars.

Dr Batista adds: 'We folded in some extra information, such as the time it takes for life to evolve on a planet, and for that we can only use what we know about life on Earth. That limits the mass of stars that can host life, as high-mass stars don’t live long enough for that.

'So unless there are hazards associated with low-mass red dwarf stars that prevent life springing up around them – such as high levels of radiation – then a typical civilisation would likely find itself living at some point in the future. We may be too early.'

Co-author Dr David Sloan, also of Oxford's Department of Physics, adds: 'This is, to our knowledge, the first study that takes into account the long-term future of our universe – often, examinations of questions like this focus on why we arrived so late.

'Our next steps are towards refining our understanding of this topic. Now that we have knowledge of a wide catalogue of exoplanets, the issue of whether or not we are alone becomes ever more pressing.'

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