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A trek to Everest base camp is helping Oxford University researchers investigate the links between heart failure and the low oxygen levels suffered by patients with a range of serious diseases.

Dr Cameron Holloway, Dr Nick Knight and Dr Andrew Murray from Oxford University's Department of Physiology, Anatomy and Genetics and the Oxford Centre for Clinical Magnetic Resonance Research were among several hundred volunteer hikers walking to the foot of Mount Everest to study the body’s response to the thin air.

The team wanted to simulate the condition of hypoxia – when the body or part of the body is deprived of sufficient oxygen. Patients with pneumonia, smoking-related diseases and some forms of heart failure suffer hypoxia.

It was Dr Holloway’s first experience of such a severe climate and he was startled by some of the findings. Among the most significant were changes to blood oxygen levels and energy synthesis.

‘I was amazed at how low the arterial oxygen levels fell in our blood,’ Dr Holloway said. ‘Saturation was in the 70 and 80 per cents during simple exercise at altitude when normally you would get worried if it dropped from normal at 98 per cent to 93 per cent.'

‘Usually that level isn’t compatible with life. If someone came in with levels that low we would rush them into intensive care.’

Another ‘huge shock’ was the 25 per cent drop in the cardiac phosocreatine/adenosine-triphosphate (PCr/ATP) ratio – a measure of the amount of energy available to the heart.

‘People with heart disease often have this ratio impaired. We experienced similar impairment, even reaching the levels of heart failure. We don’t know if it was due to adaptation to low oxygen or showed that our hearts were not coping.’

Dr Holloway’s study of 14 of the volunteers ran alongside a larger research project by Caudwell Xtreme Everest, part of the UCL Centre for Altitude, Space and Extreme environment medicine (CASE). The findings were published recently in The FASEB Journal.

Before leaving for Nepal, participants underwent wide-ranging tests, including assessments of heart, vascular, brain and exercise performance. Blood and other tests were carried out at several points during the 11-day ascent from Lukla’s Tenzing-Hilary Airport at 2,850m to 5,360m base camp.

The initial tests, which took place in Oxford, were repeated within 48 hours of the group’s return from Everest and carried out again six months after the trek ended. By then all changes to the heart and energy levels had returned to the pre-trek baseline.

Dr Holloway suspects that the findings witnessed during the Everest trip may have parallels with the cause of some forms of heart failure:

‘At base camp the symptoms we had, including breathlessness and exercise intolerance, were similar to those experienced by heart failure patients.'

‘Even a small amount of exercise was really difficult. That’s what people have to deal with when they have pneumonia or other diseases.’

Dr Holloway hopes the lessons from the study will improve care for critically ill adults and children, and even babies in incubators.

‘Now we are looking at heart failure patients to see if low oxygen is the problem and if changing oxygen pathways could improve the lives of heart failure patients. We also need to work out what is behind individual differences in the changes people experience as a result of low oxygen.’

The standard treatment for acute myeloid leukaemia, the most common type of leukaemia in adults, is chemotherapy. But in some people the cancer of the white blood cells can come back after initially successful treatment.

This is thought to be because some cancer stem cells – key cells able to drive the growth of cancers – have remained even after the chemotherapy.

Understanding more about the cancer stem cells present in leukaemia patients could help improve the ability of treatments to get rid of these cancer-driving cells.

Dr Paresh Vyas of the Weatherall Institute for Molecular Medicine at Oxford University and colleagues published a study in Cancer Cell last month that sheds new light on the different populations of stem cells present in leukaemia patients.

The work, funded by the MRC and the Oxford Biomedical Research Centre, could lead to tests that are able to track the presence of cancer stem cells in leukaemia patients, to monitor the progress of treatment or with the aim of preventing later relapse. We caught up with Paresh to learn more...

OxSciBlog: What are cancer stem cells and why are they important?
Paresh Vyas: Stem cells, in general, are primitive cells capable of continually renewing and producing many different types of cell in the body.

Cancer stem cells in particular are primitive cells that are thought to be the source of a cancer. Consequently lots of efforts are being made to characterise cancer stem cells in order to develop therapies that kill these cells and provide better treatments that cure more patients with fewer side effects.

OSB: What did you set out to investigate?
PV: We focused on one cancer called acute myeloid leukaemia. Around 2,200 people in the UK are diagnosed with this cancer every year. Unfortunately up to half of these patients relapse and the disease is very difficult to treat if it returns.

We set out to identify the leukaemic stem cells in acute myeloid leukaemia by studying bone marrow samples (the body’s factory for blood cells) from patients with the condition.

OSB: What did you find about leukaemia stem cells?
PV: We showed that the majority of patients had more than one type of stem-cell-like leukaemia cell in their bone marrow.

OSB: Does this tell us about how leukaemia arises or how the cancer persists?
PV: The confirmation that a single patient can have more than one type of cancerous stem cell driving the disease may explain why treatments for acute myeloid leukaemia are not effective in many cases.

OSB: Can we make use of this knowledge, either in treating patients or in coming up with new therapies?
PV: By identifying new cells that are responsible for driving this leukaemia, we can start to develop new and improved treatments that target these cells.

Most significantly for patients with acute myeloid leukaemia, we can also look at better ways of tracking the disease in individuals and preventing the disease returning.

We've been tracking the progress of the OuTrop Project looking to conserve the environment and wildlife of Borneo's forests.

One of the leaders of the project Susan Cheyne, of Oxford University's WildCRU, is back in the UK to talk about the progress being made and why these forests are vital to the survival of orang-utans, wild cats, and other rare species.

'We've now collected 14,000 hours of animal observations and the gibbon project has over 9,000 hours, making these among the largest studies of their kind,' Susan told us. 'The results are used for conservation purposes but are revealing many interesting discoveries on the behaviour, ecology, social structure and development of two of mankind's closest relatives.'

It's not just about apes, the team have found that Sabangau forest is a strong-hold for birds and mammals such as the elusive Bornean clouded leopard.

'We have data on 3 male clouded leopards and 1 female and we've been investigating threats to these cats including direct and indirect hunting and the possible long-term impacts of habitat loss through fires on the sustainability of the population,' Susan explains.

Along with studying the wildlife, OuTrop also funds a range of conservation activities including replanting areas of the forest and restoring natural water courses by damming artificial drainage canals. It also funds and works with local villagers to help prevent illegal logging and hunting and fight forest fires.

Susan Cheyne talks to BBC Radio Oxford about her work at 3pm on 14 February.

She is a member of WildCRU, part of Oxford's Department of Zoology.

Online stargazers have reported 90 potential new planets to Oxford University's planet seekers' website.

Planethunters.org was set up by Oxford’s Department of Physics to test NASA's Kepler project which is searching for planets in the 'Goldilocks zone', the region around a star in which planets can have liquid water and are neither too hot nor too cold for life to exist.

This week NASA confirmed the discovery of the 15th planet since the project began nearly two years ago.

The Kepler telescopes detect new planets by recording tiny changes in the brightness of stars. This dimming is caused by planets crossing in front of them. Volunteers visiting planethunters.org sort through thousands of images of stars searching for examples of these dimming events (known as 'transits') which NASA’s small team of experts may have missed.

The 90 planets, less than half of which have been picked up by NASA, are now in a queue for further observation probably using the world’s largest telescopes in Hawaii.

Arfon Smith, one of the Oxford University scientists behind planethunters.org, said: 'People have turned out to be very good at identifying potential planets and the 90 we’ve had reported so far could all be worthy of being on the Kepler list.'

'Astronomy is an incredibly competitive research area and in six months’ time someone else might claim credit for seeing one of our 90 candidates. All we are saying is that we saw them first.'

The naming of new planets is less straight forward and the International Astronomical Union [IAU] has yet to rule on how that will be done. 'Given that there are going to be millions of new planets eventually it’s highly unlikely that we will have one named after us,' Arfon said.

The findings have fuelled his passion for astronomy: 'I don’t believe in God and I’ve always wanted to know how the universe works.

'I’m interested in how good a fit are humans to living elsewhere. For example, we wouldn't necessarily need four fingers and a thumb because the pinching mechanism might be all we required.

'I think there’s a very real chance that if we met life from another planet we wouldn’t recognise it as life at all.'

Dr Arfon Smith is based at Oxford University’s Department of Physics.

The majority of hospital cases of Clostridium difficile at the John Radcliffe Hospital in Oxford are not caused by transmission of the bug within the hospital, so early results of a new project suggest.

It was one example used by Professor Peter Donnelly last night, in giving the first Oxford London Lecture at Church House in Westminster, to illustrate how the modern revolution in genetics is already beginning to affect healthcare for us all.

The research, carried out jointly by researchers at the University and the Oxford Radcliffe Hospitals through the Oxford Biomedical Research Centre, uses the latest genomic screening technologies to identify DNA variations present in the C difficile bugs causing the infection.

It works as a kind of ‘genetic fingerprinting for germs’, explained Peter Donnelly, allowing the researchers led by Professors Derrick Crook and Tim Peto to trace whether the same bug has been transmitted between patients.

C. difficile can cause infections that lead to diarrhoea and fever, often after antibiotics have been used to treat other health conditions, and can be serious or life-threatening. Significant efforts have been made by the NHS to reduce cases in hospitals and numbers have come down.

The research, taking place after these changes have been made in the NHS, are reassuring in showing most cases are from C. difficile bugs with different genetic profiles. That means these cases can’t have been down to the same bug being transmitted between patients in the hospital wards.

In his overview of recent advances in genetics for the Oxford London Lecture, Peter Donnelly looked at what we have learned since the human genome was decoded 10 years ago, and the research it had facilitated.

In particular, he outlined how technologies have allowed the identification of genetic variants –single changes in the DNA code – that are associated with increased risk of common diseases like diabetes, heart disease and many types of cancer.

Peter Donnelly has played a large role in these efforts himself as director of the Wellcome Trust Centre for Human Genetics at Oxford University.

The approach involves scanning the whole genomes of a large group of people with a condition at around 0.5m positions along the 3bn DNA letters in their genomes, and comparing these to the DNA letters found at the same positions in the genomes of a large number of healthy people. Any DNA variations that occur a lot more frequently in those with the condition can be considered to confer some kind of increased susceptibility to the condition.

The first genetic variant (associated with age-related macular degeneration) was discovered in this way in 2005. By 2007, only two years later, there had been an explosion in the genetic variants linked to different diseases, and by summer 2010 there were around 1000 variants known to be associated with 200 different diseases and conditions.

‘We know remarkably little about the biological causes of disease,’ said Peter Donnelly. ‘[Identifying these genetic variants] has given us a whole new set of clues about what is happening in the disease processes.’

The hope is that this will lead to new treatments and drugs targeted against the disease processes, and possibly new interventions to reduce someone’s risk of that disease.

Peter Donnelly noted the technological challenge in managing the huge amounts of data generated by this research – for example, 50 Tb of data will be created by a new project the Wellcome Trust Centre for Human Genetics is beginning, along with US collaborators, that will sequence the whole genomes of 2700 people with and without type 2 diabetes. But he said ‘the bigger challenge will be to translate [these new discoveries] into medical care’.

The real hope, he explained, is to be able to transform information about an individual’s genetic profile into a tailored treatment for them – personalising their medical care.

Our genetic profiles can influence how we react to drugs, including the side-effects we might experience, he said. Knowing these connections would mean clinicians could get the right dose or avoid drugs that would give that particular patient nasty side-effects.

‘Cancer is fundamentally a disease of the genome,’ explained Peter Donnelly. Underlying the development of any cancer are disruptions in the DNA in individual cells, allowing them to escape normal controls and grow without restriction to form tumours.

Just in the last year or two, it has been possible to catalogue the genetic changes found in cells taken from patients’ tumours. These early pictures of the large number of genetic changes that can build up in cancerous cells are also showing something else. Breast cancers in different people, for example, can look entirely different at the level of the genome – even though the cancers are of the same part of the body.

It may be possible soon to be able to classify patients’ tumours by their genetic profiles, suggested Peter Donnelly, enabling clinicians to make better decisions about the treatments that will work best for them.

And finally, Peter Donnelly illustrated what knowing more about our genetic profiles might mean for us as individuals. You can now send off samples of your DNA to various companies who will send back information, based on current understanding, on your relative personal risk of different diseases according to your genes.

Peter has done this himself and shared some of the results, as well as what is needed to interpret what the findings mean.

His results showed he was around 6 times more likely to suffer psoriasis during his lifetime than the general population. That’s a large increase in risk, but he pointed out that only around 2% of the population get psoriasis. If he is then at a 12-13% risk of the condition, there’s still a 90% chance of not getting it.

His risk of type 2 diabetes is a little bit greater – 1.2 times more – than the population as a whole. But he explained that this effect was more serious, as he was then at a 31% lifetime risk of diabetes because so many more people in the population develop diabetes. This finding, however, does allow him to take steps to reduce this genetic risk by making healthy lifestyle choices, something he said he is trying his best to do.

‘We live in exciting times,’ he concluded. ‘There’s a good chance that we’ll look back at the first part of the 21st century as the time when we started to understand ourselves by learning the language of genes.’