Professor Kyle Pattinson from the Nuffield Department of Clinical Neurosciences explains how brain scanning could help doctors to personalise treatment for people with chronic breathing disorders.
Ever realised you’ve forgotten your inhaler and immediately felt your breathing become more difficult? Ever wanted to walk upstairs to get something, but the thought of becoming breathless has stopped you? You’re not alone! Our brains store a phenomenal amount of information about the world, based on our past experiences. This helps us to assess situations quickly and anticipate how our bodies will respond, such as when we will become breathless. These ideas are learned and updated constantly throughout our life, and quickly adapt if we develop something like a chronic breathing disorder.
These learned ideas, or ‘priors’, are thought to not only influence our actions (such as avoiding the stairs), but can materially alter the way we perceive a symptom like breathlessness. This theory is termed the ‘Bayesian brain hypothesis’, and it explains how our priors are compared to incoming sensory information in the brain, and both pieces of information are used to create our conscious perception.
Breathlessness can be experienced by people with a wide range of conditions: those with respiratory, cardiovascular or neuromuscular diseases, as well as some people with cancer or conditions such as panic disorder. Symptoms vary, but can include hunger for air, increased breathing effort, rapid breathing and chest tightness. These breathing symptoms have been known for a long time to be influenced by psychological states such as anxiety, but also by low mood, hormone status, gender, obesity and level of fitness. However, the influence of our previous experiences and learned associations has only more recently entered into the equation.
When we have repeated or frightening exposures to breathlessness, such as an asthma attack or severe breathlessness, our brain can quickly learn and update our priors. This system is designed to help us to avoid threats and keep us safe, but generating very strong expectations (priors) about breathlessness can then exacerbate our symptoms on future occasions. What’s more, certain personailty traits such as higher anxiety, or greater body awareness may also influence this system, making some people more susceptible to developing strong expectations about their breathlessness. Once these expectations are embedded, they can be difficult to ‘un-learn’ – the brain can easily catastrophise about the potential worst case scenario, such as having another asthma attack.
Scientists at the University of Oxford are at the cutting-edge of a continually improving brain imaging technology that is being used to shed some light on what exactly is happening when we anticipate and experience breathlessness (see some examples here and here). Over the last eight years our research team has been steadily chipping away at these brain mysteries, in the hope that their findings will lead to more carefully targeted and personalised treatments for people with chronic breathlessness.
In the Nuffield Department of Clinical Neurosciences, we are using high-field functional magnetic resonance imaging to look at the brain’s workings in incredible detail. This has enabled us to start uncovering the complex neural mechanisms involved in dealing with breathlessness.
The team have been exploring brain networks of breathlessness perception in people with chronic obstructive pulmonary disease (sometimes known as emphysema or bronchitis). The most successful currently available treatment for this condition is pulmonary rehabilitation: a programme of exercise, education, and support to help people with chronic breathing problems learn to breathe more easily again. This type of rehabilitation does not influence physical lung function. That means that it must instead work by helping people to change their learned priors, which make them overestimate the threat of breathlessness (we’re back to those stairs again).
Using functional magnetic resonance imaging, we have confirmed that the people who had benefitted from this rehabilitation programme had both higher initial brain activity and greater rehabilitation-induced changes in parts of the brain linked to body symptom evaluation and emotion – the insula and anterior cingulate cortex. They are now working towards studies that can help to increase these changes in breathlessness expectations, and to identify which people in particular are most amenable to the benefits of pulmonary rehabilitation. This was the focus of our recently published study, and will help to better understand how personalised therapy may be designed for each individual.
Treating the lungs AND the brain
Clearly there can’t be a ‘one size fits all’ approach to treating debilitating perceptions of breathlessness. Current attempts to treat the complexity of chronic breathing problems have been somewhat scattered, and we must now work towards understanding the individual ‘lived experience of breathlessness’ to lead us to more carefully nuanced interventions. The different factors at play in breathlessness all need to be targeted as part of a comprehensive treatment programme: What are the brain mechanisms at work in learned expectations? How do anxiety, stress and low mood impact on breathlessness? How closely are the observable physical symptoms actually linked to lung function? Imagine the discomfort that could be reduced and quality of life that could be improved, not to mention the money that could be saved (breathlessness due to COPD costs the NHS more than £4 billion per year), if breathlessness were approached in a more holistic way.
Pulmonary rehabilitation is just one in a raft of potential behavioural and drug therapies that could be used to ease the often crippling fear of breathlessness. Only 35% of people who are prescribed pulmonary rehabilitation actually take it up (for a variety of reasons, including not being able to get out to the venues where it is run); and only 60% of those who take it up actually benefit. Therefore, more research is needed to understand the specific mechanisms of breathlessness perception, and develop different treatments that would be suitable for different people. It is the details we are gleaning about the incredibly complex brain mechanisms of symptom perception that will equip us to design more successful treatment options for those whose symptoms do not match their lung function, to bring breathlessness back under control.
Oxford researchers have conducted a new analysis which reveals a surprising twist in the tale of how fish evolved.
The ray-finned fishes are the most numerous group of backboned animals. There are tens of thousands of different ray-finned species, from angelfish to zebrafish, making up 99% of all species of fish, and 50% of all vertebrates. They are useful to humans as a source of food, and sometimes even as pets, but they are also our distant cousins. We share a common ancestor, deep in evolutionary history. We know a lot about how the other major group of vertebrates, lobe-finned fishes, evolved as they began to move onto dry land, giving rise to birds, reptiles, amphibians and mammals, including humans. However, the early evolution of the ray-finned fishes’ side of the family tree is not so well understood.
Now, an international team including researchers from Oxford University’s Department of Earth Sciences have discovered a new piece of the puzzle. They looked at polypterids, bizarre fish which live in African freshwaters. Led by Dr Sam Giles from the University of Oxford, they used CT scanning to take a fresh look at the ancestors of modern polypterids, fossilised 250 million years ago.
Although polypterids are technically ray-finned fish, they have a curious combination of features, including thick scales, lungs and fleshy fins, which make them look very ancient - they have been referred to as “dinosaur fish”. They are so strange that scientists didn’t work out that they were ray-finned fish for more than a century after they were discovered. The polypterids seem to be out of place in time, more primitive in evolutionary terms than fossilised ray-finned fish from millions of years ago.
However, the researchers discovered that the “dinosaur fish” aren’t as primitive as they seem. Looking at modern polypterids alongside fossils of their ancestors, it appears that, in fact, they developed some of their odd characteristics later in time.
“Polypterids appear to have undergone several reversals in their evolution, which has clouded the view of their position in the fish family tree,” Dr Giles explained. “It’s as if your brand-new smartphone came with a rotary dialler and without Wi-Fi; we know it’s the latest handset, but its characteristics might lead us to think it’s an older model.”
Now we understand these outwardly “primitive” characteristics for what they were, the polypterids, and their position in the lineage of ray-finned fish, start to make more sense.
“With this new analysis, we were able to iron out a lot of the wrinkles in our understanding of the sequence of evolutionary events,” Dr Giles reflected. “These results change our understanding of when the largest living group of vertebrates evolved, and tell us that ray-finned fishes dominated the seas following a major mass extinction that eradicated their closest rivals.”
“Analyses like these are powerful tools, and go to show that palaeontology doesn’t always rely on the discovery of new fossils; re-examination of old fossils using new techniques is just as important for revitalising our understanding of vertebrate evolution.”
The full paper was published in Nature as “Early members of ‘living fossil’ lineage imply later origin of modern ray-finned fishes”: DOI: 10.1038/nature23654.
Simon Hooker is a Professor of Atomic and Laser Physics at the University of Oxford, and Chris Arran and Robert Shalloo are two of his graduate students. They discuss the group's work on developing plasma accelerators for real-world applications.
In our group at Oxford's Department of Physics, we combine high-intensity lasers and plasmas to build extremely compact particle accelerators. Our recent experimental results, published in Physical Review Letters, demonstrate a new way to do this - bringing us a step closer to seeing these accelerators widely used in commercial and medical applications.
When we think of particle accelerators - machines which accelerate particles such as electrons and protons to almost the speed of light, we tend to think of the Large Hadron Collider at CERN, which is the largest machine ever built at 27 km in circumference. But of the more than 30,000 particle accelerators in operation worldwide today, fewer than 10% are used for scientific research and only 1% specifically in high energy particle physics. So what are the rest used for?
Particle accelerators have been used to investigate new fuel sources and study holy relics - but the vast majority are used in medicine and industry. In medicine, accelerators are used for the diagnosis and treatment of cancer, to produce high quality beams of X-rays, and for advanced medical imaging. In industry, accelerators are an integral part of processing a broad range of products, from treating foodstuffs for increased shelf life to microelectronics inside smartphones. In fact, it is estimated that every year accelerators treat over £350 billion worth of products. But almost all of the accelerators used for these applications rely on technology developed nearly a century ago.
In recent years, scientists around the world have been working to develop new accelerators powered by the interaction of very intense laser pulses and plasmas. In these "laser wakefield accelerators" an intense laser pulse is fired into a gas, which ionizes it to form a mixture of negatively charged electrons and positively charged ions, at temperatures approaching a million degrees. As the laser pulse travels through the plasma it pushes the plasma electrons out of its way, setting up a "plasma wake" behind it - just as a boat moving across a lake creates a wake. The alternation of positive and negative charge densities within the plasma wake sets up huge electric fields, equivalent to a voltage difference of 10 million volts across the diameter of a human hair. These intense fields can be used to accelerate charged particles to high energies in a distance hundreds to thousands of times smaller than in a conventional particle accelerators, dramatically shrinking the size and cost.
Laser-plasma accelerators have already been used to generate electron beams with similar energies to that used in synchrotron light sources - like the Diamond Light Source near Oxford, but in an accelerator stage only a few centimetres long, rather than in a stadium-sized machine. However, the lasers used could only fire a few times per second, severely limiting the applications of these compact accelerators.
We recently proposed a new approach, called the "multiple-pulse laser wakefield accelerator" (MP-LWFA) which could increase the repetition rate of laser-plasma accelerators by a factor of a thousand.
The idea is to drive the plasma wake with a train of lower energy laser pulses, rather than with a single, high-energy pulse. If the pulses are spaced correctly they "kick" the plasma in time with the plasma motion driven by the earlier pulses, in just the same way that repeated, well-timed pushes of a swing result in a large amplitude oscillation. This change of approach allows very different types of laser to be used, which can deliver thousands of pulse trains per second and with high "wall-plug" efficiency. The ultimate goal is to generate synchrotron-like electron and X-ray beams from a laboratory-scale device.
A snapshot of a laser wakefield produced in our experiment. The image shows the wake created behind a laser pulse travelling left to right, leaving behind areas of alternating positive and negative charge.
Recently we demonstrated these ideas in an experiment performed at the Rutherford Appleton Laboratory near Oxford. In that work, we fired a train of laser pulses into a plasma and measured the size of the plasma wake which was driven. We found that, just as expected, the strength of the wake was maximized when the laser pulses were separated so that they kicked the plasma in time with the plasma oscillation driven by the earlier pulses. In contrast, if the pulse separation was mismatched to the plasma oscillation then the plasma wake disappeared. Detailed analysis showed that the experimental data was in very good agreement with our theoretical models, confirming that we have a clear understanding of the physics at play.
Having demonstrated the concept, future work will be aimed at generating electron beams and working with experts in laser physics to develop an architecture for a new generation of compact laser-driven accelerators with properties useful for real-world applications.
Faith Fordham is on a journey.
After serving almost seven years as a Royal Navy medic, in Afghanistan, she was discharged from service in 2011. Faith left the military with a number of physical injuries and a Post Traumatic Stress Disorder (PTSD) diagnosis.
Despite the challenges she has faced, Faith has just successfully completed a PGCE qualification in Chemistry at Pembroke College, and will soon take part in the Invictus Games Toronto 2017. Canadian-born Faith is set to compete in the rowing, powerlifting, athletics and swimming events at the international sporting competition for wounded, ill and injured military personnel and veterans.
She talks to Scienceblog about going from the military frontline to the classroom, and what taking part in the Games’ means to her.
What inspired you to become a science teacher?
When I left the military my world was torn apart. It was my life and all that I wanted my life to be.
I lost my identity and in searching for a new one, applied for a science PGCE. I got offered a place and with a lot of encouragement from friends and military peers, I decided to accept it. I’ve not looked back since.
My depression always clouded my future, which made it impossible to set any goals. Invictus has given me an escape and allowed to me to maintain bonds with my military peers. Having something to focus on has shown me that I do not need to be defined by my illness.
How has living with a mental health condition affected your studies?
A mental health condition changes your entire life outlook.
When I left the military I became severely depressed. There have been long periods of time where I have been unable to leave my house and at one point even attempted to take my own life. Over the last few years’ things have improved - but I still have dark days and always will.
My depression always clouded my future, which made it impossible to set any goals. However, having something to focus on has shown me that I do not need to be defined by my illness.
Pembroke College have always been supportive, giving me an extension when needed and acknowledging the needs of my condition even when I did not. I do not want my mental health to define me, so sometimes push myself to do things, like go to college, when I’m not in the right frame of mind. My Disability Mentor and I had a great relationship and at those times they would tell me that I shouldn’t be there, and to go home and take care of myself.
How has training and preparing for the Invictus Games supported your recovery?
Since starting training, my confidence has risen and I have found a reason to get up in the morning. I am slowly figuring out who I am and where I belong.
When I first started training my goal was to lose weight. But I hit my target and needed another goal to aim for, so decided to apply for the Games’.
What does taking part in the Invictus Games mean to you?
My Invictus experience has given me an escape and allowed to me to maintain bonds with my military peers. It was hard to adjust to society after active duty, but through the event I can get my fix and then come back to the real world.
Since leaving the Royal Navy I have had a number of surgeries, but when training for the Games’ I forget about it all. One of my rowing teammates has lost three limbs. But when we are competing you don’t notice his injuries, only his strength. When we are out in public I see how others look at him though, they fixate on his injuries. But that is not how he - or any of us, see ourselves.
Lots of my students are from disadvantaged backgrounds, I want them to hear my story and know that if you keep going and pushing, you can always turn a corner.
How have your experiences influenced your teaching style?
I’m definitely more understanding of their experiences.
Because of my hardships students find it very easy to relate to me. During my school teaching placement I noticed that being able to relate to a mentor is really important to young people. Lots of their role models, like the musician Eminem, have overcome their own circumstances.
I’m not afraid to open up to them or share my experiences. Lots of my students are from disadvantaged backgrounds - some are young carers etc. I want them to hear my story and know that if you keep going and pushing, you can always turn a corner. Even if you lose something you can progress and make something of your life in other areas.
Why did you choose to teach chemistry?
I always liked science as a child and chemistry was actually my worst subject. But the experimental side of things has always appealed to me.
What do you like most about teaching?
I enjoy helping young people to expand their horizons and discover new things - particularly young girls. I did my teaching placement at a mixed school and an all girls’ school, and noticed that in mixed science class rooms, girls seem to say less.
Young girls need to know that stereotypes do not matter. Science – particularly physics and chemistry, is for them too. I loved my time at Oxford University, and think their community outreach work, visiting schools and showing students what a career in science looks like, really helps in this area.
What is next for you?
In early September I start my Newly Qualified Teaching Year (NQT) at Rye Saint Anthony School, Oxfordshire, and of course have the Invictus Games in Toronto at the end of the month.
Long-term, I want to focus on my teaching career and hopefully progress to Head of Department one day. I also want to complete a Masters Degree in teaching and science – I’m just deciding which to do first.
Like anyone who has been in the military, I can never sit still for too long.
Mathematicians are known for having a brilliant way with numbers, but to have impact beyond their field they need to have an altogether different skill: the ability to communicate.
The George Pólya Prize for Mathematical Exposition, from the Society for Industrial and Applied Mathematics (SIAM), acknowledges and celebrates academics who are both great thinkers and writers.
This year’s recipient Professor Nick Trefethen, Head of the Numerical Analysis Group in the Oxford Mathematical Institute, has been celebrated for bridging the communication gap with his publications. The Society highlights the ‘exceptionally well-expressed accumulated insights found in his books, papers, essays, and talks... His enthusiastic approach to his subject, his leadership, and his delight at the enlightenment achieved are unique and inspirational, motivating others to learn and do applied mathematics through the practical combination of deep analysis and algorithmic dexterity.’
Professor Trefethen discusses receiving the honour and why his field is the fastest moving laboratory discipline in STEM.
Congratulations on your award, how did you react when you found out you had won?
I was thrilled. There are many accolades to dream of achieving in an academic career, but I am one of the relatively few mathematicians who love to write. So, to be acknowledged for mathematical exposition is important to me. My mother was a writer and I guess it is in my blood.
What is numerical analysis?
Much of science and engineering involves solving problems in mathematics, but these can rarely be solved on paper. They have to be solved with a computer, and to do this you need algorithms.
Numerical analysis is the field devoted to developing those algorithms. Its applications are everywhere. For example, weather forecasting and climate modelling, designing airplanes or power plants, creating new materials, studying biological populations, it is simply everywhere.
It is the hands-on exploratory way to do mathematics. I like to think of it as the fastest laboratory discipline. I can conceive an experiment and in the next 10 minutes, I can run it. You get the joy of being a scientist without the months of work setting up the experiment.
How does it work in practice?
Everything I do is exploratory through a computer and focused around solving problems such as differential equations, while still addressing basic issues. In my forthcoming book Exploring ODEs (Ordinary Differential Equations) for example, every concept measured is illustrated as you go using our automated software system, Chebfun.
How has your research advanced the field?
Most of my own research is not directly tied to applications, more to the development of fundamental algorithms and software.
But, I have been involved in two key physical applications in my career. One was in connection with transition to turbulence of fluid flows, such as flow in a pipe; and recently in explaining how a Faraday cage works, such as the screen on your microwave oven that keeps the microwaves inside the device, while letting the light escape so that you can keep an eye on your food.
You got a lot of attention for your alternative Body Mass Index (BMI) formula, how did you come up with it?
My alternative BMI formula was *not* based on scientific research. But, then again, the original BMI formula wasn’t based on much research either. I actually wrote a letter to The Economist with my theory. They published it and it spread through the media amazingly.
As a mathematician, unless you’re Professor Andrew Wiles or Stephen Hawking for example, you are fortunate to have the opportunity to be well known within the field and invisible to the general public at the same time. The BMI interest was all very uncomfortable and unexpected.
Why do you think so few mathematicians are strong communicators?
I don’t think this is necessarily the case. One of the reasons that British universities are so strong academically, is the Research Excellence Framework, through which contributions are measured. But, on the other hand the structure has exacerbated the myth that writing books is a waste of time for academic scientists. The irony is that in any real sense, writing books is what gives you longevity and impact.
At the last REF the two things that mattered most to me, that I felt had had the most impact, were my latest book and my software project, and neither were mentioned.
In academia we play a very conservative game and try to only talk about our latest research paper. The things that actually give you impact are not always measured.
What are you working on at the moment?
I just finished writing my latest book on ODEs (due to be published later this year), which I am very excited about.
Have you always had a passion for mathematics?
My father was an engineer and I sometimes think of myself as one too - or perhaps a physicist doing maths. Numerical Analysis is a combination of mathematics and computer science, so your motivations are slightly different. Like so many in my field, I have studied and held faculty positions in both areas.
What is next for you?
I am due to start a sabbatical in Lyon, France later this year. I'll be working on a new project, but if you don’t mind, I won’t go into detail. A lot of people say that they are driven by solving a certain applied problem, but I am really a curiosity-driven mathematician. I am driven by the way the field and the algorithms are moving. I am going to try and take the next step in a particular area. I just need to work on my French.
What do you think can be done to support public engagement with mathematics?
I think the change may come through technology, almost by accident. You will have noticed over the last few decades, that people have naturally become more comfortable with computers, and I think that may expand in other interesting directions.
The public’s love/hate relationship with mathematics has been pervasive throughout my career. As a Professor, whenever you get to border control you get asked about your title. ‘What are you a Professor of?’ When you reply, the general response is ‘oh I hated maths.’ But, sometimes you'll get ‘I loved maths, it was my best subject’, which is heartening.
What has been your career highlight to date?
Coming to Oxford was a big deal, as was being elected to the Royal Society. It meant a lot to me, especially because I am an American. It represented being accepted by my new country.
Are there any research problems that you wish you had solved first?
I’m actually going to a conference in California, where 60 people will try to prove a particular theorem; Crouzeix’s Conjecture. By the end of the week I will probably be kicking myself that I wasn’t the guy to find the final piece of the puzzle.