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MRI scans improve prostate cancer detection

MRI scans improve prostate cancer detection

The research, led by the National Institute for Health Research (NIHR) and Universities of Bristol, Ottawa, Exeter and Oxford, combined the results from seven studies covering 2,582 patients.

The researchers found that the use of pre-biopsy MRI combined with targeted prostate biopsy was better than a biopsy alone in detecting prostate cancers that are likely to need treatment, despite the differences between the seven individual studies. Using pre-biopsy MRI led to fewer biopsy cores being taken per procedure, which in turn reduced side effects, and may potentially lead to avoiding biopsies for some men.

Taken together, this new evidence supports the use of pre-biopsy MRI in diagnostic pathways for suspected prostate cancer.

Prostate biopsies can cause side effects, and do not always identify the severity of a cancer when it is present. MRI scans are increasingly being used before undertaking a prostate biopsy as part of the clinical pathway to diagnose prostate cancer, but their use isn’t yet widespread in many countries. In the UK, pre-biopsy MRI has recently been recommended by the National Institute for Health and Care Excellence (NICE).

The researchers looked at existing research in this area, focusing on men who had never had a prostate biopsy before.

Professor Richard Bryant, an Academic Consultant Urologist at the Nuffield Department of Surgical Sciences at Oxford University and one of the authors of the paper, said: ‘This research adds to the growing body of evidence that targeting biopsies through pre-biopsy MRI, in men being checked for possible prostate cancer, leads to a more accurate sampling of the prostate gland. It could also potentially lead to fewer biopsies and less chance of a misleading biopsy result, through better initial sampling.

‘Whilst there are obviously benefits for men to have a prostate biopsy if indicated, so that we can diagnose and then treat clinically significant prostate cancer, if we can reduce the potential side effects and increase the accuracy of the initial biopsy procedure, then that will be better for patients.’

Dr Martha Elwenspoek, Research Associate at the NIHR Collaboration for Leadership in Applied Health Research and Care West (NIHR CLAHRC West) and the University of Bristol, said: ‘Our findings suggest that using an MRI to guide prostate biopsies is superior to performing a biopsy alone. This is increasingly used in the UK but isn’t yet common practice in many other countries. However our work shows that this approach is better at detecting cancer that requires treatment, while also potentially avoiding some unnecessary biopsy procedures.

‘This chimes with the findings of another recent paper looking at this issue.’

The full publication, ‘Comparison of multiparametric magnet resonance imaging and targeted biopsy with systematic biopsy alone for the diagnosis of prostate cancer: a systematic review and meta-analysis‘, is available to read in the journal JAMA Network 

Materials provided by Oxford University

Blue Tang Fish

‘The Nemo effect’ is untrue: animal movies promote awareness, not harm

The emotive warnings were made because of global reports that its precursor Finding Nemo had inspired a surge in purchases of clownfish, which in turn caused environmental and animal harm. This became known as ‘the Nemo effect’.

The most high profile of the warnings came from the voice of ‘Little Dory’ herself – Ellen DeGeneres, and largely all the appeals focused on stopping viewers from buying pets linked with the movie.

Results from scientists at the University of Oxford published in the journal Ambio today show that the links between consumer-demand for wildlife and blockbuster movies are largely unfounded.

Their results suggest that exposure to these movies does not increase demand for live animals, but can instead drive information-seeking behaviour.

The researchers looked at data on online search patterns, from the Google Trends platform, fish purchase data from a major US importer of ornamental fish and visitation data from 20 Aquaria across the US.

Their results show that, counter to popular narratives, by focusing on lesser-known species, blockbuster movies can actually bring attention to species that would normally not receive attention, illuminating animal diversity and environmental threats that are of societal concern.

The scientists say it is hard to determine exactly how reports of ‘the Nemo effect’ originated, although past research mentions a number of press articles in the UK, USA and Australia, published shortly after the release of the movie. These were amplified by numerous other outlets around the world.

Allegations have also been made in the media linking the Harry Potter movie series and Zootopia to spikes in demand for certain species. In both cases separate studies found that these allegations have not been supported by the evidence. Similar allegations have been made for movies as diverse as the Teenage Mutant Ninja Turtles and Jurassic Park.

The scientists’ research suggests that there is no evidence that the ‘Nemo effect’ is real.

Lead researcher, Diogo Veríssimo, from the Department of Zoology, University of Oxford, said: ‘We think these narratives are so compelling because they are based on a clear causal link that is plausible, relating to events that are high profile – Finding Dory was one of the highest-grossing animated movies in history.

‘My research looks at demand for wildlife in multiple contexts. As such, I was intrigued as to whether the connection between these blockbusters and demand for wildlife was as straight-forward as had been described in the media. My experience is that human behaviour is hard to influence, particularly at scale and it seemed unlikely that movies like Finding NemoFinding Dory and the Harry Potter series indeed generated spikes in demand for the species they feature.

‘Our results suggest that the impact of movies is limited when it comes to the large-scale buying of animals. There is, however, a clear effect in terms of information-seeking which means that the media does play an important role in making wildlife and nature conservation more salient. This is particularly the case for animation movies which are viewed by a much more diverse group of people than, for example, nature documentaries.’

The researchers plan to follow up this study with an examination of the role of nature and wildlife documentaries in shaping behaviours towards nature: for example, the impact of the BBC Blue Planet series on behaviours around plastics and of the documentary Black Fish on attitudes towards cetacean captivity.

Diogo Veríssimo (Department of Zoology, University of Oxford) collaborated on this paper with Sean Anderson (Pacific Biological Station, Fisheries and Oceans Canada) and Michael Tlusty (School for the Environment, University of Massachusetts Boston).

Engineering new signalling networks to produce crops that need less fertiliser

Engineering new signalling networks to produce crops that need less fertiliser

Published in Nature Communications today, the team of plant scientists, microbiologists and chemists used synthetic biology techniques to design and then engineer a molecular dialogue between plants and the bacteria surrounding their roots in a zone called the rhizosphere. This synthetic signalling system could be a vital step towards successfully engineering nitrogen-fixing symbiosis in non-legume crops like wheat and maize.

Enhancing the root microbiota has enormous potential for improving crop yields in nutrient-poor soils and reducing chemical fertiliser use.

Joint lead author, Dr Barney Geddes, from Oxford’s Department of Plant Sciences, said: ‘Plants influence the microbiota of their rhizosphere by sending out chemical signals that attract or suppress specific microbes. Engineering cereal plants to produce a signal to communicate with and control the bacteria on their roots could potentially enable them to take advantage of the growth-promoting services of those bacteria, including nitrogen fixation.

‘To do this we selected a group of compounds normally produced by bacteria in legume nodules, called rhizopines. First, we had to discover the natural biosynthetic pathway for rhizopine production, and then design a synthetic pathway that was more readily transferred to plants. We were able to transfer the synthetic signalling pathway to a number of plants, including cereals, and engineer a response by rhizosphere bacteria to rhizopine.’

Joint lead author, Dr Amelie Joffrin, at Oxford developed a new stereoselective synthesis of key rhizopine. She said: ‘The synthetic chemistry was essential to provide compounds that enabled the investigation of rhizopine biosynthesis and its transfer from bacteria to plant. In particular, the rhizopines produced allowed us to confirm which was the naturally active enantiomer (“hand”) of a key bioactive compound.’

Dr Ponraj Paramasivan, joint lead author at Cambridge’s Sainsbury Laboratory, explained how the team transferred the rhizopine synthesis genes into barley to assess whether they could engineer rhizopine synthesis in cereals.

She said: ‘We confirmed the barley synthesised and then exuded rhizopine to its rhizosphere. We then measured the signalling between barley roots and rhizosphere bacteria and found a significant level of communication was occurring in most bacterial colonies. These results mean that we could potentially use this transkingdom signalling pathway to activate root microbiota to fix nitrogen, and a host of other plant growth-promoting services such as producing antibiotics or hormones or solubilising soil nutrients.

“A key advantage of this synthetic signalling pathway is that only the specific crop plant that is engineered to produce the signal will benefit. This means that weeds that currently benefit just as much as the target crop from the application of chemical fertilisers, will not benefit from these enhanced plant-microbe associations as they do not produce this novel signalling molecule to communicate with bacteria.”

Future work in the Poole, Oldroyd and Conway laboratories will focus on how plants can control key processes in root bacteria such as nitrogen fixation, phosphate solubilisation and plant growth promotion. This opens up the world of the bacterial microbiome and its diverse metabolism to control by plants and in particular the cereals. It is likely to be a key component in attempts to engineer nitrogen fixation into cereals.

Read the full paper in Nature Communications.

Materials provided by University of Oxford

New approach to reducing damage after a heart attack

New approach to reducing damage after a heart attack

During the emergency procedure used to reopen the blocked artery causing a heart attack, smaller “micro” blood vessels can remain constricted causing significant damage. A new study led by Associate Professor Neil Herring and published in the European Heart Journal has established a key cause behind this constriction and identified a potential therapeutic target to block the mechanism behind it.

Cardiovascular disease is the main cause of death in the UK and throughout the Western World. One of the most common ways in which that manifests is through heart attacks, which occurs when one of the heart’s arteries is blocked. During a heart attack part of the heart starts to die, which causes pain in the chest and can be life-threatening.

Large heart attacks are treated with an emergency procedure to reopen the blocked artery using a balloon and metal tube called a stent. Whilst this procedure is often life saving, in around one third of cases smaller “micro” blood vessels beyond the stent remain constricted causing significant damage. The cause of these micro-vessels being very tightly constricted has so far been unclear.

A new study led by Professor Neil Herring has shed light on why this may happen. Innovative new research has uncovered evidence that the issue relates to the amount of stress the patient experiences during the heart attack. As part of the stress response, a neurotransmitter called Neuropeptide-Y (NPY) is released which causes micro-vessels in the heart to constrict. Furthermore, their data has demonstrated that patients with high NPY levels tend to go on to experience more heart damage.

To establish these results, the team studied patients who had experienced large heart attacks. They measured the levels of NPY both within the heart and peripheral blood. Alongside this, they took accurate and sophisticated measures of how constricted the small blood vessels were at the time. Through state of the art scans at 48 hours and 6 months after heart attack, researchers were able to see how much damage had been done to the heart. ‘We were able to correlate quite nicely the levels of NPY in the heart with how constricted the blood vessels were and even how much damage was done to the heart 6 months later,’ said Professor Herring.

The next step was to understand the mechanism behind how NPY causes this constriction. By studying isolated blood vessels in an animal model, researchers identified a key receptor that NPY binds to to cause the construction. They were then able to compare these results with samples of human hearts taken at the time of surgery, which clearly demonstrated that the receptor is also present in the human heart.

The crucial finding at this stage indicated that drugs that block the NPY receptor can reduce the damage of a heart attack in an experimental model. ‘That gives us real impetus to say if we can come up with a drug that we can use in humans that can block that receptor, then this may be a really good new treatment that we may be able to give to heart attack patients,’ said Professor Herring. Further studies are needed to establish whether NPY blocking drugs reduce the damage caused by a heart attack in patients and help improve survival.

The study is in collaboration with the Herring Group, the Oxford Acute Myocardial Infarction (OxAMI) Study led by Professor Keith Channon from the Oxford Heart Centre and the Radcliffe Department of Medicine, and Professor Kim Dora at the Department of Pharmacology. The research was supported by the British Heart Foundation and has been published in the European Heart Journal.

The full publication, ‘Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction,’ can be read in the European Heart Journal.

Materials provided by University of Oxford

Scientists map huge variety of animal life cycles

Scientists map huge variety of animal life cycles

Their findings, published today in Nature Ecology and Evolution, come from a detailed assessment of 121 species ranging from humans to sponges, may have important implications for conservation strategies and for predicting which species will be the winners and losers from the global environmental crisis.

Pace of life” relates to how fast animals reach maturity, how long they can expect to live, and the rate at which they can replenish a population with offspring. “Shape of life”, meanwhile, relates to how an animal’s chance of breeding or dying is spread out across its lifespan.

The research is the result of a collaboration between scientists from Oxford University, the National University of Ireland Galway, Trinity College Dublin, the University of Southampton, and the University of Southern Denmark.

The wide range of animal life cycles

Animal life cycles vary to a staggering degree. Some animals, such as  the turquoise killifish (a small fish that can complete its life cycle in 14 days) grow fast and die young, while others, like the Greenland shark (a fish that glides around for up to 500 years), grow slowly and have extraordinarily long lifespans.

Similarly, the spread of death and reproduction across animal life cycles also varies greatly. Salmon, for example, spawn over a short period of time with the probability of dying being particularly high both at the start of their life cycle and when they reproduce. Fulmars and some other sea birds, on the other hand, have wider time periods of reproduction and face relatively similar chances of dying throughout their lives.

Humans and Asian elephants have long lifespans and face a relatively low risk of mortality until later ages, but have a fairly narrow age range for reproduction due to having both long juvenile periods and as they can live after the reproductive part of their life-cycles. Both species share a similar lifespan with the Australian freshwater crocodile, but the crocodile has a completely different reproductive strategy – its reproduction is spread relatively evenly throughout its lifespan but its young have a low chance of reaching adulthood and reproducing.

The puzzle of different life cycles

Why animal life cycles vary so much has long been an important puzzle that scientists have sought to solve. Among the reasons are that understanding why animals age, reproduce and grow at different rates may:

1)    help shed light on the evolution of ageing itself

2)    help identify how species will respond to global environmental change

In their study, the scientists used population data to compare detailed life cycles for species ranging from sponges to corals, salmon to turtles, and vultures to humans. By mapping 121 life cycles, the scientists noticed that certain animal ecologies and physiologies were associated with certain life cycles.

Associate Professor in Ecology at the University of Oxford, Dr Rob Salguero-Gómez, co-senior author, said:

“Since the times of Aristotle, and much later also recapitulated by Darwin and many more to follow, biologists have been amazed by the amount of variation in strategies that organisms develop to live in different environments. How fast to grow (or not), how long to live (or not), and when/how much to reproduce (or not) are the building blocks that allow for different species to persist in their climates, past, current, and – importantly due to climate change – future. This work provides a comparative glance at the variation in life history strategies among animals, and it remarkably highlights important commonalities in the ways that both animals and plants go about making a living and adapting to different environments. Classical works in life history theory predicted a single way to structure life strategies. Recent work that we have done in my group, the SalGo Team, with plants and now here with animals shows the range of possibilities is much wider than previously suspected.

“The unparalleled wealth of animal demographic schedules used in this research opens up new exciting ways to explore what are the most common strategies used by different species to thrive in their environments, but also to use demographic models to make predictions about what species will be the winners and losers of climate change.”

Lead author, Dr Kevin Healy, who conducted the research at Trinity; now Lecturer of Zoology at the National University of Ireland Galway, said:

“When we mapped out the range of life cycles in the animal kingdom we saw that they follow general patterns. Whether you are a sponge, a fish or a human, your life cycle can, in general, be described by two things – how fast you live and how your reproduction and chance of dying is spread out across your lifespan.

“As we expected, species with low metabolic rates and slow modes-of-life were associated with slower life cycles. This makes sense; if you don’t burn much energy per second, you are restricted in how fast you can grow. Similarly, if you are an animal that doesn’t move around a lot, such as a sponge or a fish that lives on the sea bed, playing a longer game in terms of your pace of life makes sense as you may need to wait for food to come to you.”

Conservation implications

The scientists also investigated whether certain life cycles made animals more susceptible to ecological threats, by looking for associations between an animal’s life cycle and its position on the IUCN red list of endangered species.

Professor of Zoology and Head of the Zoology Department at Trinity, Yvonne Buckley, co-senior author, said:

“We found that extinction risks were not confined to particular types of life history for the 121 species. Despite these animals having very different ways of maintaining their populations, they faced similar levels of threat.

“Populations of a particular species, like the Chinook salmon or Freshwater crocodile, vary more in how mortality and reproduction are spread across their life-spans than they vary in their pace of life. This is important for the animal populations that we need to conserve as it suggests it may be wiser to consider actions that boost reproduction and/or impart bigger effects on the periods of the life cycles when mortality and reproduction are more likely – rather than simply aiming to extend the lifespans of these animals.”

Journal: https://www.nature.com/articles/s41559-019-0938-7

Materials provided by the University of Oxford

Magnetic monopoles - Particle physics

Magnetic monopoles make acoustic debut

Magnetic monopoles are fundamentally important but highly elusive elementary particles exhibiting quantized magnetic charge. The prospect for studying them has brightened in recent years with the theoretical realization that, in certain classes of magnetic insulators, the thermally excited states exhibit all the characteristics of magnetic monopoles.

Now, a collaboration led by Professor JC Séamus Davis and Professor Stephen J Blundell of the University of Oxford’s Department of Physics has developed a new approach to detecting and studying these ‘emergent’ magnetic monopoles – including the discovery that, when amplified, the noise they make is audible to humans. The findings are published in the journal Nature.

In 2018, Professor Blundell and his colleagues Dr. Franziska Kirschner and Dr. Felix Flicker predicted that the random motion of magnetic monopole inside these compounds would generate a very specific kind of magnetization noise.

This means that a crystal of one of these magnetic insulators should spontaneously generate wildly and randomly fluctuating magnetic fields both internally and externally, as the monopoles move around. The catch was that these fields vary rapidly and randomly at every point so that the net fluctuating field through a sample was predicted to be near one billionth of the Earth’s field.

In response, Professor Davis and colleague Dr Ritika Dusad built an exquisitely sensitive magnetic-field-noise spectrometer based on a superconducting quantum interference device – a SQUID.

Professor Davis said: “Virtually all the predicted features of the magnetic noise coming from a dense fluid of magnetic monopoles were then discovered emerging from crystals of Dy2Ti2O7. Extraordinarily, because this magnetic monopole noise occurs in the frequency range below 20kHz, when amplified by the SQUID it is actually audible to humans.”

Professor Blundell added: “What makes magnetic monopoles fascinating is that they ‘emerge’ from a dense lattice of magnetic monopoles, and this makes their motion highly constrained – very different from a typical gas of charged particles. This observation led us on a search for the signature of this constrained motion in the magnetic noise spectrum. These exciting results open up the possibility of using magnetic noise to study many other exotic magnetic systems containing different species of emergent particles.”