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How zebrafish could help unlock new approaches to treating human stress

In the thick of job hunting and her postdoc, Professor Soojin Ryu’s sleepless nights provided her first personal insight into the impact of stress on the brain and behaviour. The revelation would shape a research career that is transforming understanding of stress.

“One day it struck me – when I’m stressed I don’t sleep. I got to thinking about the impact of that on the body and on a person’s life, and the consequences are huge. If you’re stressed and not sleeping you can start behaving like an unpleasant human being – agitated and short-tempered, and ultimately you can become really sick. As a modern society, we’ve decided to ramp up our stress hormone to the point that it’s life-threatening. I find that fascinating.”

Now, Soojin has joined the University of Exeter as Mireille Gillings Professor of Neurobiology, heading up a group that studies zebrafish to examine how acute and chronic stress change behaviour and its longer term consequences on the body and brain.

In her early career, in Berkley, Soojin worked in cells, but found the research ultimately unsatisfying. “I spent a number of years working on cell culture, but then I’d ask myself – ‘ is that what’s really happening in the body’?”

She wanted to work in small vertebrate, in which changes in response to hormonal fluctuations occur quickly. She chose zebrafish as the best option, pioneering a new animal model to study stress by discovering important aspects of how they respond to stress.

“Of course, zebrafish are really very different from humans, but it’s important to recognise which aspects are similar,” Soojin said. “I realised that the evolutionarily ancient brain stress response is similar in both humans and zebrafish.”

At the Max Planck Institute in Germany, Soojin started her own research, creating a genetically-modified zebrafish in which scientists are able to manipulate stress hormone levels at will. Published in Nature Communications, the work helped address some of the difficulties researchers had encountered in studying stress. In her last post at the University of Mainz, Soojin was part of a network applying basic stress research to human resilience.

“Some level of stress hormone is beneficial, but once it hits a certain level, it becomes detrimental to the body and brain,” explained Soojin. “Stress can be life-saving. Our stress hormone levels rise shortly before we awake and it helps ensure our systems are ready to respond. The stress hormone is fundamental to animal survival. We need the right level of stress for the appropriate situation and our bodies need to be able to regulate that to be healthy. We know that depressed people have different patterns of stress hormone where that regulation can falter.

“For the first time, our zebrafish model allows us to precisely control both the stress hormone level and the duration which is necessary to understand different effects of stress. That’s why it’s so exciting for the future of stress research.”

One important aspect of securing the Gillings Fellowship was a commitment to promoting women in science, an issue close to the heart of philanthropist Mireille Gillings. Soojin has mentored a number of female scientists and has organised workshops and meetings for women in neuroscience, to discuss the issues they identified as important. Her interest also stems from a personal passion driven by her need to balance work with parenting her eight-year-old daughter Leia. “As a mother, I am deeply committed to helping women combine scientific career with family,” she said.

“I’m delighted to join Exeter. Having seen how successful our model is, I’m passionate about collaborating with people who are working on human health to form a translational network to ensure it benefits people as swiftly as possible. Exeter has a strong focus on mental health and has amazing growth potential. I’m looking forward to working with my new colleagues to explore new treatment targets.”

Mireille Gillings Fellow will innovate to improve lives of frail older people

Over her career, Professor Sallie Lamb has developed a huge respect for the older people she works with on her ground-breaking rehabilitation programmes.

Professor Lamb, Mireille Gillings Professor of Health Innovation, has recently joined Exeter, having worked with a wide range of patients over the years, and has a specialism in frailty.

“I really admire how tenacious so many older people are,” said Sallie, who joins Exeter from Oxford University. “They’re the most vulnerable, yet they’re the ones who try the hardest and complain the least. I think it’s because they already know what losing their mobility feels like. They want to do everything they can to prevent that further and to get better, and they’re willing to fight for it.”

Sallie’s Fellowship at Exeter will help her develop more tools for older people to combat frailty. She has already had huge success in other areas, developing a programme for the common and often debilitating issue of lower back pain that was acknowledged as one of the most successful innovations in the NHS. The programme uses a cognitive behavioural approach to promote appropriate physical activity, which can effectively reduce symptoms over the long term.

“If you’re in a lot of pain, you feel like you can’t move and that you should lie still in bed – but that creates a vicious cycle of making the symptoms worse. With back pain, you really need to move to relive the symptoms. Our programme teaches people how to pace themselves and what type of activities to select, plus what to do if you get a setback.”

As a marker of the success of the programme, thousands of health professionals have so far undertaken a free online learning course, known as a MOOC, to upskill in the programme.

At Exeter, Sallie’s research will focus on frailty, an area where the College of Medicine and Health has existing expertise including Professors Louise Allen and Vicki Goodwin. “It’s a really exciting opportunity,” said Sallie. “There’s a huge opportunity to drive forward innovation and improve the health and wellbeing of older people – and particularly to improve mobility, which is key to a healthy and active life.

“The funding from the Gillings Foundation is really going to accelerate the development of a strong research programme to complement the existing research going on at Exeter. It’s a huge boost and will really accelerate getting this research to a point where it benefits people in need.”

Sallie is known for her rigorous approach to research, previously leading the Oxford Clinical Trials Research Unit, and will contribute to expanding capacity and expertise in clinical trials and medical statistics in the South West. .

A key aspect of the Fellowship appointments is a commitment to promoting women, a passion shared by entrepreneur Mireille Gillings. Sallie said she found herself in a role model position by leading by example, and as mother to 7-year-old Emelia, she is passionate about promoting work-life balance while enabling career progression.

“I’m also really committed to promoting a culture of teamwork between academic and professional services staff,” said Sallie. “People in professional services roles are absolutely critical and it’s important that’s recognised and valued.

“I’m really excited to join so many excellent scholars at Exeter, at such a dynamic time of growth and development.”

New Fellowship will tackle overlap between cancer and diabetes

Around 415 million people worldwide have diabetes, while 100 million people have cancer. They are unequivocally two of today’s greatest global health challenges. In bringing her world-leading knowledge of cancer to Exeter’s renowned diabetes research team, Professor Chrissie Thirlwell aims to benefit people with both conditions.

The newly-appointed Mireille Gillings Professor of Cancer Genomics will investigate the increased risk of some cancers in type 2 diabetes and obesity.

“If you have type 2 diabetes, you have a 20 – 30 per cent increased risk of developing certain cancers including bowel, liver and pancreatic cancer. The potential mechanisms underlying this increased risk are complex and incorporate lifestyle, dietary and other known risk factors such as obesity. The first step will be to determine any specific mechanisms associated with type 2 diabetes or obesity individually.

“The Mireille Gillings Fellowship has given me the infrastructure and opportunity to bring together my experience of cancer genomics and the wealth of world class research in diabetes and obesity at Exeter. It will accelerate our understanding of the increased cancer risk through utilising genomic data that has already been generated while producing new epigenetic data which will inform us about the impact of lifestyle on cancer risk.”

Chrissie’s expertise neatly crosses over with several research strengths at Exeter’s College of Medicine and Health and the wider university. She has natural synergy with Professors Sian Ellard and Andrew Hattersley in genomics, including a shared involvement with Sian in the 100,000 Genomes Project. Chrissie will join the Genomic Medical Centre team bringing her cancer genomics experience at a pivotal time when the 100,000 genomes project is being completed and DNA sequencing is becoming a routine part of patient care through the delivery of the next 5 million genomes.

The research funded by the Mireille Gillings Fellowship dovetails with several other groups in the RILD allowing new and exciting collaborations including with Professor Tim Frayling in large-scale genome-wide association studies looking for patterns in genes, and Professors Jon Mill and Katie Lunnon in epigenetics, or the study of how genes are activated, and Prof Lorna Harries in how genes are transcribed. Like Professor Noel Morgan, she is also already looking at clusters of cells known as islets in the pancreas, and how they contribute to the development of pancreatic neuroendocrine tumours.

Chrissie plans to apply these burgeoning collaborations to her new research and her body of work studying neuroendocrine tumours – rare tumours that can grow in different body organs. The international collaborations she has established to aid understanding and improve treatment have made her a global authority.

A large aspect of the Gillings Fellowship, supported by entrepreneur Mireille Gillings, is a commitment to promoting women in leadership roles. Through her involvement in UCL Cancer Institute’s Athena SWAN team, where they secured a coveted silver award to recognise commitment to equality, Chrissie realised the extent of a problem that had been invisible to her. “I was at a stage in my career when I wasn’t even aware that so few senior roles were held by women. I naively thought a lot of it was down to personal choice around work-life balance and families. Through working with industry during the UCL Cancer Institute Athena SWAN process, I learned that there were many incredibly capable women who really wanted those opportunities – they just weren’t getting them. I was struck how the statistics are alarmingly similar across the public and private sectors in that only 20% of senior leadership roles are held by women.

“It has to be about the right person with the right skills to do the job, there’s so much evidence that having diversity across all areas in leadership roles and on executive boards, leads to a far more productive workforce.”

Now, the medical oncologist plans to continue her clinical work alongside her research, joining the Royal Devon & Exeter NHS Foundation Trust. She has bold ambitions for the region. “I’m really keen to link with other trusts and create a European Centre of Excellence for the management of neuroendocrine tumours in the South West. We have the expertise across the region and it would mean a huge benefit to patients.

“It always blows people away when I mention the statistic that one in two people born after 1960 will be diagnosed with cancer at some point in their lives. Yet I’ve seen through my working life that prognosis and treatments are continuously improving. We’re moving towards a time where cancer becomes a chronic disease that people live with, rather than die from. There have been recent improvements in early diagnosis, and Exeter’s research has contributed to that through Professor Willie Hamilton’s team, however there’s still more work to be done .
“We’ve also seen major advances in treatment, particularly through immunotherapy, which harnesses the patient’s own immune system to fight cancer cells. Being part of those advances make my job extremely rewarding. When a patient is referred to an oncologist, you generally look after them for life. You get to know them and their families really well, and these days, there’s so much more we can do to improve their prognosis and enable them to live as normal life as possible during and after treatment.”

Chrissie arrives at Exeter at an exciting time. The diabetes research team recently secured a major £6 million award as part of the Government’s modern industrial strategy. The award recognises excellence with capacity to grow, and aims to enable the research to reach the next level, through academic recruitment and investment in infrastructure and facilities.
A keen open water swimmer who swam the English Channel while completing her PhD, Chrissie is looking forward to exploring all that the South West can offer. “The lifestyle is the icing on the cake for me in moving to Exeter,” she said. “It’s such an amazing time to come here. I‘m passionate about education and the expanding Medical Sciences and Medicine programmes present some really exciting opportunities, alongside the many research opportunities. I’ve had an incredible welcome so far and I’m really looking forward to getting stuck in and making a difference.”

University of Exeter, University of Sanctuary Award Presentation, 20 November 2019

Welcome everyone, I’m Janice Kay, of the University of Exeter. It’s wonderful to see so many of you for this award ceremony. It is a moment of celebration, and one that has a very deep and important meaning. On behalf of the senior management team and our whole university community, we are absolutely delighted to have achieved University of Sanctuary status. This award is a clear marker of our commitment, our progress and our success in creating a welcoming and supportive environment for refugees and asylum seekers.

I quote directly from the Universities of Sanctuary organisation: Universities, as key institutions within our society, have a responsibility to support people from all walks of life to reach their potential. The notion of sanctuary fits with the values and strategic plans of most universities; it contributes towards progress in inclusivity, diversity, and sustainability. It means taking a practical, public step towards inclusion, and countering discourses of xenophobia and racism both within and outside university life.

The idea of Universities of Sanctuary has grown from the Cities of Sanctuary scheme. Exeter has had an active and engaged City of Sanctuary group since 2014 with a thriving network of supporters. I am extremely proud that our students and staff instrumental in setting up the City of Sanctuary group. Not only that, they have gone on take action here at the university to enable us to become a University of Sanctuary, a university that welcomes refugees into our community and actively supports them.

This award recognises the efforts of many members of our community. I would particularly like to  recognise the work of last year’s Guild and specifically the former Students’ Guild President Grace Frain and previous Vice-President for Welfare and Diversity Rose Ahier. They championed and drove forward our activities to become a University of Sanctuary. It is wonderful to see Grace here today. Working alongside them has been our Sanctuary Scholars, our academic lead Dr Nick Gill and our Head of Student Immigration Services Jim Price, as well as many others.  Our ongoing thanks go to all of our local partners who work with the university to provide advice, guidance and support to our scholars. I would especially like to thank Refugee Support Devon and our local City of Sanctuary group.

This is a moment for celebration but I want to reflect for a moment on how important it is that we provide a safe and welcoming university community for refugees and asylum seekers. Refugees come to our country to seek safety from fear and persecution, be it for reasons of race, religion, nationality, membership of a particular social group or political opinion. Latest government figures indicate that there have been over 32,000 applications for asylum in the last 12 months. These numbers include people for whom a higher education in their country of birth may have been an unattainable goal. For some, exploring and fulfilling their potential through academic exploration would never have been an option. Universities in our country can help. Higher education has a longstanding tradition of providing sanctuary to academics and students. We are proud to be able to continue this tradition. The University of Sanctuary status shows we are doing this, and our commitment to going further. Equal Access to Higher Education is of course a universal right under Article 26 of the Declaration of Human Rights.

We have very many initiatives at Exeter to support refugees either directly through education and training or indirectly through our research which contributes to the evidence base and body of knowledge about forced migration and frail and failed states. Our academics and students have set up language exchange programmes, they conduct outreach activities using drama as a medium of engagement and have set up new information resources. Dr Nick Gill will share more about these later.

One of our most fundamental initiatives is the Sanctuary Scholarship programme which started in 2017. The scholarships enable the cost of tuition to be waived and provide support for living costs. We have now supported nine studentships and we are fortunate to have one of our Sanctuary Scholars with us today.

One of our Sanctuary Scholars has taken part in a video project called Lost in the Noise, which has been pioneered by Harry Bishop, a former student and Vice President for Community and Welfare at our Cornwall campus and who is now a member of staff in Cornwall. This project has sought to profile individuals and students whose voices may otherwise indeed have become ‘lost in the noise’. It is vital that we hear these stories and that we start to understand the experiences of others. This is a powerful route to becoming a more diverse, compassionate, progressive and culturally competent community. Thank you to the scholar for sharing their experiences so candidly in this film and to Harry for your project which has enabled this to happen. This film extremely impactful and brings to life the importance of universities as a place of sanctuary.

So once again, thank you for joining us to mark our award as a University of Sanctuary. It is an important milestone for us as an institution and one from which we will continue to build.

The enemy of my enemy is my friend

The year is 2050, the stench of plague fills the air and 10 million people are dying from cuts and grazes due to an enemy that cannot be seen. You would be forgiven for believing that we had entered a dystopian, parallel future, but alas not. This is the current future of mankind if we do not address the ever-growing threat: antibiotic resistance.

Whether we want to face it or not, our antibiotics are failing. Drugs that we have relied upon to so effectively treat bacterial infections are no longer working due to these crafty bugs becoming resistant to them. Over time, bacteria have evolved to survive antibiotics, with this “survival of the fittest” process resulting in populations of menacing “superbugs”. No matter how many different antibiotics we throw at these resistant microbes, some can no longer be killed and so what were once minor infections become fatal.

So how can we fight back!?

One avenue is to discover and develop new antibiotics. However, this has proven to be extremely costly and difficult, so alternative options are being explored. Mankind’s possible saviour: bacteriophages.

Bacteriophages, or simply phages, are viruses that infect and kill bacteria. Just as humans get viruses like flu, bacteria suffer from their own invaders which hijack the bacterial cell and turn it into a virus making factory, before killing them. With their large bulbous head and spindly legs (think War of the Worlds alien invader fighting ships), they are perfectly adapted for attaching to bacteria. Phages are the optimal killing machines. Currently, phages are not widely used to treat infections in the Western world as not enough is known about them. If we want to be able to harness the power of these microscopic bacteria killers, then we need to know more about how they work.

Most research studying bacteria and phages use methods that involve growing billions of cells in a test tube, and looking at how fast the population grows and dies on average. But this is not always the most informative. Imagine you want to know how fast humans run 100m. Someone tells you the average time is 15 seconds. Although all humans, not everyone would take 15 seconds. Clearly if Usain Bolt ran the race he would be much quicker, and the man who decided to hop all the way much slower! This also applies to bacteria. Even though they should all be identical, individual bacteria can behave very differently.

My work lets us identify the Usain Bolts and the Hop-Alongs of the bacteria world, as well as many others in between. I want to know which responses occur when we expose bacteria to phages and how this may affect the killing ability of these viruses.

Erin Attrill, Living Systems Institute

I use technology called ‘microfluidics’ that allows me to isolate and experiment on individual bacteria. With ‘micro’ meaning small, and ‘fluidics’ relating to the movement of liquids, I perform experiments on bacteria with equipment no larger than a postage stamp. Using networks of thousands of tiny channels, I can trap single bacteria in their own tiny chamber under a microscope and watch what happens when I add phages. Over the course of a day, I can continually monitor and photograph the same cells and record whether they are growing, dividing and even the exact point at which they lyse – that is, when they burst open releasing hundreds more phages.

I have observed that although all identical, some bacteria die instantly, but others grow much faster and divide multiple times before finally lysing hours later. Perhaps most importantly, some bacteria in the experiments are not killed by the phages at all. These bacteria survive the exposure and fill their chambers with more bacteria offspring. What makes these cells special and able to survive is unclear, and one aim of my work is to use microfluidics to try and understand why.

It is important to understand these differences to be able to optimise how many phages would be needed to eradicate the bacteria in a human as a potential treatment. If most bacteria are killed with two hours of phage treatment, a person may begin to look healthy, but if the “Usain Bolt” variants survive, then they could cause the infection to return. A longer dose or a higher concentration of phages may be required to eradicate the entire population so we need to fully understand how the different cells behave.

There is no need to be afraid of the word ‘virus’ – the good news is that phages cannot infect human cells. These minuscule invaders are the enemy of bacteria and so we should harness their power to defeat our bacterial foes. As stated, the enemy of my enemy is my friend. So let’s welcome in the age of the phage.

Erin Attrill, Living Systems Institute, University of Exeter

This article was the runner up in Max Perutz Science Writing Competition 2019.
Read all the shortlisted articles here https://mrc.ukri.org/documents/pdf/max-p-shortlist-articles-2019/

Startup Weekend Exeter 2017

The weekend of November 17 – 19 saw the University of Exeter Business School transformed into an incubation space for Exeter’s brightest minds and entrepreneurial spirits. Now in its fourth year, Techstar’s Startup Weekend Exeter is a 54-hour startup sprint designed to guide entrepreneurs in shaping their innovative ideas into business realities over the course of just three days. The weekend captures the essence of the entrepreneurial journey; full of energy, hard work, camaraderie, and hours of high-intensity fun as teams compete to determine who wins 1st overall, people’s choice, or best purpose driven idea.

Sponsored by the University of Exeter Business School and SetSquared, many postgraduate students from the 2018 Exeter MBA cohort were in attendance, alongside a healthy mix of undergraduate students and members of the Exeter community. The weekend kicked off Friday evening, with a rousing welcome party hosted by TechStar facilitator David Andersen, followed by inspirational speeches from local social entrepreneur Kalkidan Lagasse and executive coach Ian Hale.

This year’s event centred around business with a purpose, and both Hale and Lagasse represented the power of purpose-led business by recounting their inspirational success stories. Lagasse began her retail business, Sancho’s Dress, as a way to bolster the income of her Aunt, a talented seamstress struggling to make ends meet in Lagasse’s home country of Ethiopia. Lagasse began her business as a student at the University of Exeter, selling her Aunt’s homemade scarves at a booth in the forum. She then engaged with the ThinkTryDo! Student Startup programme, and soon grew her business into a successful brick and mortar shop on Fore Street. Recently, Lagasse has expanded her business to fill a second retail space. She sells organic, cruelty-free clothing, jewellery and accessories.

Now it was time for Friday’s main event: the pitches! Participants were asked to come prepared with a business concept, and had only 60 seconds to present their idea to the Startup Weekend Exeter delegation. In all over 30 pitches showcased an incredible array of creative, innovative and inspiring ideas – from making a wood pulp substitute out of sugar cane, to creating building materials out of used plastic bottles, to stilettos capable of converting into flats by detaching the heels! Once all the pitches were heard, participants cast their votes for the top ideas.  In the end, a total of eight teams were formed, and it was the teams with representation of a variety of demographics and an expansive array of skills, that were most successful.

Once assembled, teams quickly got to work brainstorming on how to bring their ideas to life, and created their agendas for the weekend. The task: ideate, validate, create, and actuate! Typically, ideation begins with an expansive view, then focuses in on a realistic attainment, the creation of a prototype, or minimum viable product (MVP).

On Saturday, teams were expected to validate their ideas in the marketplace. This involved taking to the streets of Exeter, and discovering whether or not consumers would actually be interested in their business. Saturday also featured think tank sessions with an impressive array of mentors from all across the tech and entrepreneurial communities. Mentors conducted individual sessions with each team, offering tech support, logistics advisement, business development expertise, and much more.

Startup Weekend Exeter is a hectic, busy, and exciting time. Teams often find it hard to break away from the work to eat and relax. Thankfully, the amazing organising team had refreshments and relaxation covered with comfy couches, table tennis, and delicious free food all weekend long! Participants enjoyed the delights of Spanish paella, Mexican tacos, and authentic Sri Lankan cuisine, alongside sandwiches from Pret-a-Manger, snacks, and sweets to keep their energy levels up and brains firing on all cylinders.

On Sunday, teams continued their frenetic pace, turning their ideas into action. They finalised their MVPs, put the final touches on their presentations, and squeezed in a few more sessions with the mentors. By late afternoon, the judges arrived and it was time to compete!

Judges for Startup Weekend included:

Antonia Power, General Counsel for Blur Group

Richard Eckley, Senior Investment Analyst for Crowdcube

Christine Allison, Director of Roborough House Associates

Stuart Robinson, Director of the Exeter MBA

Ideas were assessed according to their validity in the market, strength of their business model, and execution and design. The judges then chose the team that had presented the most convincing business and awarded the prize for best purpose driven idea and also handed out the award for the People’s Choice.

In closing the event, TechStars facilitator David Andersen said:

“Startup Weekend Exeter was a really special experience. I think there were some great teams, with great energy and great ideas. Participants here were really open-minded and keen to do new things. Basically, everything we could throw at them, they took on with a positive mindset. It really says a lot about the community here in Exeter, and I would love to see that spread after the weekend. That’s what the Startup Weekend is all about: inspiring the participants to go out and change the world.”

Special thanks to the University of Exeter Business School, the ThinkTryDo Student Startups team, Bunzl catering, Pret-a-Manger, and all of our wonderful mentors, judges, and participants.

Written by Jessica Ilyas

Aphantasia: 10,000 people make contact over visual imagery

'Heartbeat 1', Susan Aldworth 2010

‘Heartbeat 1’, Susan Aldworth 2010

Since we coined the term ‘aphantasia’ in a brief scientific paper last year (Cortex 2015; 73:378-380: Read manuscript), there has been a remarkable surge of interest in the extremes of the human experience of visual imagery: both in those of us who lack the ability to visualise at will – with aphantasia – and in those with superabundant imagery – hyperphantasia. When asked to visualise a sunset, for example, people with aphantasia are unable to conjure any kind of image to mind, and will often have assumed that terms like the ‘mind’s eye’ are purely metaphorical. At the other end of the spectrum, people with hyperphantasia describe imagery so vivid that they can find it difficult to be sure whether an image was perceived or imagined. Coverage in the press, on TV, radio and the web throughout the world, including the BBC’s on-line vividness questionnaire, has led to over 10,000 contacts from interested individuals, most of them falling at one or other extreme of the vividness spectrum. We are tremendously grateful to the several thousand people who have by now completed and returned our questionnaires: these paint a much more detailed picture of these phenomena than we could provide before. Thank you so much for doing this!

The final analysis of this wealth of data will take a while, but some patterns have already emerged. A first reaction, which came as a welcome surprise, was gratitude: people with aphantasia, in particular, were glad to have a handy term to describe this subtle but distinctive feature of their experience. Many participants have told us how they found it hard to explain this to others: they often met with disbelief. The new term seems to be useful.

Some sub-groups have come to light. The scientific literature already spoke of a link between low imagery vividness and prosopagnosia – difficulty, often lifelong, in recognising faces. This link is a recurring theme in the questionnaires. We were not too surprised by a second association: a small proportion of participants have described a diagnosis of autistic spectrum disorder (asd). Alterations in the ability to imagine have long been regarded as a key feature of asd, and visualisation is a key ingredient of imagination (though not an indispensable one, as we will see).  A third sub-group also makes good intuitive sense: many folk with aphantasia report that their autobiographical memory, for personal events like holidays and weddings, is less rich that that of their friends and relations: for most of us visualisation is a big part of recollection. But none of these associations is true for everyone: there are many shades of aphantasia.

These shades have some other expressions. Some people with aphantasia, probably the majority, dream visually: but others do not. Some can ‘imagine’ in other modalities, hearing with the mind’s ear for example, but others can’t. Does this make a nonsense of the notion of aphantasia? We think not. We know that the brain activity involved in visualisation is complex and ‘distributed’, involving a widespread network of brain areas. Given this complexity, it is not too surprising that visualisation can be disrupted in a wide variety of ways. In particular, it is understandable, in neurological terms, that dreaming and wakeful imagery can behave differently in aphantasia.

We are learning other fascinating things from our participants. While most people with aphantasia describe this as a lifelong characteristic, others have reported the loss of imagery, due to brain injury or to psychological factors: we are very keen to learn more about these. We also hope to learn much more about the large group of highly creative individuals who have contacted us: I had not anticipated so much pleasure from looking at the art of aphantasic painters or from reading the prose of aphantasic novelists. Visualisation is clearly not a prerequisite for creativity.

Much has been written and broadcast about aphantasia over the past year. Our website gives links to several of these outputs . My personal favourites include James Gallagher’s original BBC broadcast, two personal accounts written by highly creative people with aphantasia, Blake Ross’s Facebook post (A personal account by Blake Ross) and Dustin Grinnell’s article in New Scientist (Dustin Grinnell in New Scientist) and a recent radio portrait by Sarah Jane Hall (The Mind’s Eye – BBC Radio 3 ‘Between the Ears’ programme).

So far most of our knowledge of aphantasia has come from first person testimony. This is the right (and really the only) place to start the exploration of this topic, but we are keen to ‘triangulate’ our knowledge by correlating first person evidence from questionnaires with data from neuropsychological tests – of autobiographical memory or face recognition for example – and from brain imaging techniques. We have begun a pilot study with local participants who are within striking distance of Exeter. We hope to have some preliminary answers over the coming year. At present the project is relying heavily on the enthusiasm of a small group of academic colleagues and undergraduate interns who have kept the project on the road: thanks to you, also! We are applying for research funds that will enable us to extend this work. We are considering a crowd funding appeal – you may be hearing from us 🙂

We have one further plan: at our Eye’s Mind project conference in May this year, in addition to a lively group of imagery researchers, we had probably the largest ever gathering of people with aphantasia from around the world, from Finland to the States. There was enthusiasm for a meeting dedicated to aphantasia: we hope to organise this sometime next year.

This research depends entirely on the generosity of those who are sharing their experience and time. This blog is an opportunity to report back on recent progress, and to thank you for your contributions. We aim to write regular updates as the story develops.

Aurel Sari: Biting the Bullet: Why the UK Is Free to Revoke Its Withdrawal Notification under Article 50 TEU

aurel-sari‘There is no going back.’ These were the words of Lord Pannick, uttered before the High Court in response to the question whether the United Kingdom could rescind its notification to withdraw from the European Union once issued under Article 50 TEU (Santos and M v Secretary of State for Exiting The European Union, uncorrected transcripts, p. 17). The claimants and the Government appear to agree on this point and accept that the UK cannot reverse its notification of withdrawal.

It is easy to see why this position should be attractive to both parties. For the Government, it means that once the notification has been issued in accordance with the UK’s constitutional requirements, it would be shielded from any subsequent domestic legal challenge. For the claimants, the irreversibility of the withdrawal notification is of ‘vital importance’ (uncorrected transcripts, p. 14). It is this irreversibility which, in their submission, pre-empts the powers of Parliament if the Government were to issue the notification without first obtaining the Parliament’s authorisation to do so.

The significance of this point was not lost on the Lord Chief Justice. He declined an invitation by counsel to assume that the withdrawal notification was irreversible and insisted that it was ‘absolutely essential’ for the Court to decide whether it was irrevocable or not (uncorrected transcripts, p. 192). In response, Lord Pannick confirmed that it was his position, as a matter of law, that there is no power to revoke the notification.

Earlier, Lord Pannick illustrated his position with the following analogy (uncorrected transcripts, p. 19):

I say my case is very simple. My case is that notification is the pulling of the trigger. And once you have pulled the trigger, the consequence follows. The bullet hits the target. It hits the target on the date specified in Article 50(3). The triggering leads to the consequence, inevitably leads to the consequence, as a matter of law, that the treatise cease to apply and that has a dramatic impact in domestic law.

Unfortunately for Lord Pannick, the analogy does not withstand closer scrutiny.

The applicable rules of interpretation

Whether a withdrawal notification is reversible or not is a question that turns on the interpretation of Article 50 TEU. Since Article 50 TEU forms part of an international agreement, its interpretation is governed not by English law, but by the rules of international law. Of course, as is well known, the Court of Justice of the European Union adopts a teleological approach to the interpretation of the EU’s founding Treaties which differs from the general rule of treaty interpretation laid down in Article 31 of the Vienna Convention on the Law of Treaties (VCLT). In particular, the Court lays greater emphasis on the aims and objectives of European integration than Article 31 VCLT might warrant (see Gardiner, Treaty Interpretation, pp. 136–137).

Leaving aside the longstanding doctrinal debates about the autonomous nature of the EU legal order, the fact remains that the founding Treaties of the EU are instruments of international law. It is therefore perfectly appropriate for a domestic court to construe Article 50 TEU by applying the rules of interpretation set out in the VCLT. In fact, this seems even more appropriate in the light of the subject matter of Article 50 TEU. It is no coincidence that the German Federal Constitutional Court interpreted Article 50 TEU against the background of the relevant provisions of the VCLT in its judgment in the Lisbon case (para 330).

What, then, are the applicable rules of interpretation? According to Article 31(1) VCLT,

A treaty shall be interpreted in good faith in accordance with the ordinary meaning to be given to the terms of the treaty in their context and in the light of its object and purpose.

Article 50(2) TEU stipulates that the Member State wishing to withdraw from the Union must notify the European Council of its intention. However, the text is silent as to whether a Member State subsequently may revoke its notification. In the absence of express terms, we have to consider whether an answer emerges from the text, context and the object and purpose of the treaty by implication.

The purpose of Article 50 TEU

According to Article 1 TEU,

By this Treaty, the HIGH CONTRACTING PARTIES establish among themselves a EUROPEAN UNION, hereinafter called “the Union”, on which the Member States confer competences to attain objectives they have in common.

It is difficult to find a more succinct statement of the object and purpose of the TEU: the establishment of an organisation upon which the Member States confer certain competences to attain certain shared objectives. These objectives are set out in greater detail in Article 3 TEU, while the scope of the EU’s competences is defined in Articles 3–6 of the Treaty on the Functioning of the European Union (TFEU). Article 5 TEU declares that the Union must act within the limits of the competences conferred upon it by the Member States and that competences not conferred upon the Union remain with the Member States. In Declaration 18 made appended to the Lisbon Treaty, the Member States recall these points and add that it is for them to increase or reduce the competences conferred upon the Union.

What emerges from these provisions is that the Union’s competences are based on the consent of its Member States and that the authority to increase or reduce these competences (sometimes described as Kompetenz-Kompetenz) remains firmly within their own hands. Article 50 TEU takes the principles of consent and conferral to their logical conclusion and confirms the right of a Member State to withdraw from the Union. In the words of the German Federal Constitutional Court, the ‘right to withdraw underlines the Member States’ sovereignty… If a Member State can withdraw based on a decision made on its own responsibility, the process of European integration is not irreversible.’ (Lisbon case, para 329). Against this background, we may conclude that the purpose of Article 50 TEU is to confirm in express terms the Member States’ ability to withdraw from the EU and to lay down the procedures for doing so.

The arguments against revoking the withdrawal

In his submissions before the High Court, Lord Pannick relied on three arguments to suggest that the UK would not be able to revoke its withdrawal notification once issued (uncorrected transcripts, p. 16–17):

Article 50 is deliberately designed to avoid any such consequence. There is no mention of a power to withdraw. And the very possibility of a power to withdraw a notification would frustrate, again, Article 50(3), which sets out in the clearest possible terms, what the consequences are of giving the notification under Article 50(2).

It is convenient to consider these arguments in reverse order.

  1. Frustrating the procedures

First, Lord Pannick suggests that revoking the withdrawal notification would frustrate the consequences attached to the notification by Article 50(3) TEU. According to that provision,

The Treaties shall cease to apply to the State in question from the date of entry into force of the withdrawal agreement or, failing that, two years after the notification referred to in paragraph 2, unless the European Council, in agreement with the Member State concerned, unanimously decides to extend this period.

Once notified, the withdrawal is inevitable, says Lord Pannick. That is the point of his bullet analogy: once fired, the bullet has to hit its target, either upon the entry into force of the withdrawal agreement, two years after the date of withdrawal notification or at the end of any extension period agreed between the UK and the European Council. There are two flaws with this reasoning. First, the completion of the procedures described in paragraphs (2) and (3) of Article 50 TEU is conditional upon the withdrawal notification. There is no logical reason why that withdrawal notification may not be revoked before those procedures are completed. To use Lord Pannick’s analogy, nothing prevents the UK from firing a blank round. Second, the procedures listed in Article 50(3) TEU need not reach their end point. Article 50(2) TEU imposes an obligation on the Union to negotiate and conclude an agreement with the withdrawing Member State. No corresponding duty is imposed on the withdrawing Member State itself. At first sight, it might seem reasonable to assume that such a duty must be implied. However, for the purposes of the withdrawal agreement, the withdrawing State is essentially treated as a ‘third country’ (cf Article 218(1) TFEU), as evidenced by the fact that pursuant to Article 50(4) TEU, the withdrawing State shall not participate in the discussions or decisions by the European Council or Council concerning the negotiation and conclusion of the withdrawal agreement. Consequently, it would be absurd if the withdrawing Member State were thought to be bound by the principle of sincere cooperation under Article 4(3) TEU in these matters. In any event, the terms of Article 50(3) TEU make clear that at most, the withdrawing Member State is under an obligation to negotiate, but not necessarily conclude, a withdrawal agreement with the EU (in other words, the duty is for a pactum de negotiando, not a pactum de contrahendo). This is so because Article 50(3) TEU envisages that the withdrawal agreement may fail to enter into force at all, which is precisely why it provides for the two-year time period as a fall-back solution. However, that two-year time period may be extended by the mutual agreement of the withdrawing Member State and the European Council. The extension is not subject to any conditions. Consequently, the two sides may agree to an indefinite extension of the two-year period if they so wish. To use the bullet analogy again, the target may keep on moving indefinitely and the bullet may never hit home.

Notifying an intention to withdraw from the Union does not necessarily mean that the procedures triggered thereby have to be completed. Nor do these procedures inevitably have to lead to the termination of the applicability of the Treaties to the withdrawing Member States.

  1. No express power to revoke

Lord Pannick also relies on the fact that Article 50 TEU does not provide for the power to revoke the withdrawal notification in express terms. This argument is unconvincing. The competences of the EU depend on the consent of the Member States. Competences not conferred upon the EU remain with the Member States. Consequently, in so far as Article 50 TEU recognises the unilateral right of a Member State to withdraw its consent, that withdrawal can only be subject to those conditions which are expressly stipulated in Article 50 TEU. Put differently, the burden of proof is not on the withdrawing Member State to demonstrate that it has the legal capacity and authority to retract its withdrawal notification, but on the EU or its remaining Member States to show that it lacks that capacity.

At this point, it is once again necessary to recall that the Treaties are instruments of international law. As the European Court of Justice has acknowledged, the EU must respect international law in the exercise of its powers (Case C-286/90, Poulsen and Diva, para. 9). Pursuant to Article 68 VCLT, a notification to withdraw from a treaty in accordance with its provisions may be revoked ‘at any time’ before the notification takes effect. In the present case, this means that the UK would be able to revoke its withdrawal notification before the withdrawal agreement it may conclude with the Union enters into effect or before the two-year time period or the extension period agreed with the European Council runs out. The EU is not a party to the VCLT and as such it is not directly bound by Article 68 VCLT. Whether the rule forms part of customary international law, which would be binding on the EU as such, is subject to debate. However, it is worth noting that the International Law Commission, which drafted what later became Article 68 VCLT, took the view that ‘the right to revoke the notice is really implicit in the fact that it is not to become effective until a certain date’ (Draft Articles on the Law of Treaties with Commentaries, p. 264). This point applies with full force to Article 50 TEU.

State practice offers several examples of States revoking their decision to terminate their membership in an international organization, though the exact legal characterisation of some of these examples is open to discussion (see Wessel, You Can Check Out Any Time You Like, But Can You Really Leave?, p. 6). Nevertheless, the practice of the International Labour Organisation in particular suggests that the possibility to retract a withdrawal notice before it takes effect is accepted. It is also useful to point out that States may withdraw their intent to be bound by an international agreement, as the United States did in relation to the Rome Statute, or withdraw their application to become members of an international organisation, as Switzerland recently did in relation to the EU. Of course, one should be careful not to read too much into these examples, even by way of analogy. However, they do underline that States enjoy a wide measure of discretion to withdraw instruments and notifications they make in relation to treaty actions.

  1. The design of Article 50 TEU

Finally, Lord Pannick argues that Article 50 TEU was deliberately designed to avoid the possibility that a Member State might revoke its withdrawal notice. There is no evidence to support this view. The preparatory work of the intergovernmental conference which drew up the Treaty of Lisbon is not in the public domain. However, Article 50 TEU reproduces verbatim, subject only to minor editorial changes, Article I-60 of the Treaty establishing a Constitution for Europe. The negotiating history of that provision establishes very clearly that the right to withdraw from the Union was intended to be unilateral. Amendments attempting to tie this right to substantive conditions or to the successful conclusion of a withdrawal agreement were rejected (see CONV 672/03, pp. 10–12). As a note from the Praesidium of the European Convention explained, ‘it was felt that such an agreement should not constitute a condition for withdrawal so as not to void the concept of voluntary withdrawal of its substance’ (CONV 648/03, p. 9). This desire was reflected in the very title of Article I-60, which read ‘Voluntary withdrawal from the Union’.

The significance of this negotiating history is that it fully confirms the interpretation and conclusions reached earlier. The unilateral nature of the right to withdraw means that it is for the United Kingdom to decide both when to notify the European Council of its intention to withdraw and whether or not to revoke that notification. This position may please neither the claimants nor the defendant, but this is where the law stands.

Aurel Sari is a Senior Lecturer in Law at the University of Exeter, specializing in public international law. His work focuses mainly on questions of operational law, including the law of armed conflict, the legal status of foreign armed forces and the application of human rights law in deployed operations. He is a Fellow of the Allied Rapid Reaction Corps.

(Suggested citation: A. Sari, ‘Biting the Bullet: Why the UK Is Free to Revoke Its Withdrawal Notification under Article 50 TEU’, U.K. Const. L. Blog (17th Oct 2016) (available at https://ukconstitutionallaw.org/))

Abstract Expressionism: how New York overtook Europe to become the epicentre of Western art

João Florêncio, University of Exeter

A new exhibition, Abstract Expressionism, opens at London’s Royal Academy this weekend. It is the first major survey of the movement since 1959. Abstract expressionism is often considered the first artistic movement to shift the centre of Western art from Europe to the US, and more precisely New York. But what is it, and how did this happen?

Associated with a group of artists working in New York in the 1940s, abstract expressionism came to be known as the quintessential American and modern art movement. Heirs to the progressive abandonment of figurative and naturalist painting styles that had been taking place in Europe since the early 20th century, the painters associated with the movement came to be known for their innovative use of new synthetic industrial paints, large scale canvases, and the development of very individual abstract styles.

Some of the most easily identifiable include Franz Kline’s quick and simple brushstrokes, at times likened to Japanese calligraphy; the drips and rapid splatters of Jackson Pollock; Robert Motherwell’s large repeated ovals and rectangles; and Mark Rothko’s large blocks of colour.

Franz Kline, Vawdavitch, 1955.
© ARS, NY and DACS, London 2016

Despite often being seen as “childish” painting that “anyone could do”, abstract expressionism has a history that is more interesting than we might suspect at first. Because the emergence of the movement in the 1940s and its internationalisation in the 1950s wasn’t only due to the work of its artists. It was also due to both the art criticism and political environments of its time. So much so that we cannot think abstract expressionism without considering the work of critics such as Clement Greenberg and the role of art as a cultural weapon during the Cold War.

A European story

Writing at the same time as the abstract expressionists were developing their signature styles, Greenberg became the critic that most famously endorsed the movement. He claimed it represented the most “advanced” form of Western art. To justify this, Greenberg looked at the work of older European artists such as Manet, Monet, Cézanne and Picasso, arguing that European painting had been progressively moving away from representations of the three-dimensional world outside. According to him, this was also accompanied by a progressive flattening of the pictorial space.

Greenberg argued that this showed an increasing concern with investigating the potential and limitations of the elements that belonged exclusively to the medium of painting: a flat canvas with specific dimensions (length and width) upon which paint is applied. All historic examples of paintings that give the impression of three-dimensional space on canvas, all painting that tries to mimic the world outside of it, were, for Greenberg, paintings that tried to conceal their true nature.

Mark Rothko, No. 15, 1957.
© 1998 Kate Rothko Prizel & Christopher Rothko ARS, NY and DACS, London

What is crucial here is that, by producing this narrative of European art, Greenberg was able to claim that, for the first time ever, the most “advanced” form of Western art was no longer being produced in Europe but instead in New York. For him, it was painters like Pollock, Motherwell, De Kooning, Rothko, Kline, and Newman that were now, thanks to the new abstract languages they were developing, carrying on the work that had begun with the European avant-gardes. European artists, he argued, had not been able to carry this to completion, due, in part, to the weight of tradition, something that America did not have to carry.

So it was in large part due to critics like Greenberg, but also collectors like Peggy Guggenheim, and curators like MoMA’s Alfred H Barr, that abstract expressionism eventually gained momentum among the art glitterati of New York in the 1950s, despite never being popular among the wider American public.

Lee Krasner. The Eye is the First Circle, 1960.
© ARS, NY and DACS, London 2016

Cold War art

But there is also politics to consider. Abstraction had been allowed to thrive in part due to the earlier sponsorship of Franklin Roosevelt’s New Deal, which saw an incredible amount of government funds being used to directly employ artists and commission new public artworks in the aftermath of the Great Depression. Most of the works funded by that programme were American regionalist paintings and large social realist murals. But some of the funds were also used to support the early work of some of the artists whose career would eventually progress towards what came to be known as abstract expressionism.

Willem De Kooning, Woman II, 1952.
© 2016 The Willem de Kooning Foundation/Artists Rights Society (ARS), New York and DACS, London 2016

But perhaps one of the most iconic contributors to the dissemination of the movement as the culmination of Western art history was the Cold War. In the 1950s, at the peak of the ferocious anti-Communist sentiment of the McCarthy era in the US, the agendas of institutions like MoMA in New York and critics like Greenberg converged with the political interests of the CIA. Such convergence led to a series of exhibitions that would tour Europe during the Cold War years. The most famous of those was MoMA’s The New American Painting, which came to Europe in 1958-59. This show was responsible for bringing abstract expressionism to all major European capitals, including West Berlin.

Whether or not these exhibitions were funded or facilitated by the CIA, as some have convincingly argued, they were certainly responsible for cementing the perception of America as the legitimate heir of European aesthetic and political values. Against a USSR perceived as totalitarian and oppressive, with state-sanctioned socialist realism coming across as kitsch and formulaic propaganda, abstract expressionism, with its variety of individual voices and painterly styles, would eventually become a symbol of the autonomy, liberty and creative freedom allegedly enjoyed by all in the West. These were values that, from then on, became manifest in the generalised perception of the US as the ultimate beacon of Western culture.

The Conversation

João Florêncio, Lecturer in History of Modern and Contemporary Art and Visual Culture, University of Exeter

This article was originally published on The Conversation. Read the original article.

Multiple sclerosis survivors swear by hyperbaric oxygen – but does it work?

Dr Paul Eggleton, Senior Lecturer in Immunology in University of Exeter Medical School and Visiting Professor University of Alberta writes about the use of oxygen therapy for patients with MS.

This article first appeared in The Conversation.  Conversation logo

Paul Eggleton, University of Exeter

There is no cure for multiple sclerosis (MS) yet. As a complex neurodegenerative disease of the brain, it is incredibly difficult to treat. Despite the development of new and sophisticated therapies to control the inflammation and physical symptoms of the disease, these treatments don’t work for everyone. This is because MS comes in many guises and one treatment does not fit all. Perhaps for this reason people with MS are turning to alternative means of controlling their condition.

Many of the 100,000 people with MS in the UK have taken charge of managing their treatment. With the assistance of 60 or more independent charitable MS therapy centres, people with the disease regularly enter a chamber and breathe oxygen under moderate pressure (hyperbaric oxygen). Some people have done so for more than 20 years.

The air we breathe contains 21% oxygen, but 100% oxygen is considered a drug and is prescribed in hospitals to aid people’s recovery. In the case of MS, people self-prescribe the hyperbaric oxygen, which is delivered to them by trained operators. But does breathing pure oxygen under pressure on a weekly basis do them any good?

The idea to use oxygen as a treatment for MS began over 45 years ago. In 1970, two Romanian doctors, Boschetty and Cernoch, treated patients with brain injuries with pressurised oxygen to help more oxygen enter their tissues – oxygen helps protect nerve cells from damage and maintains the integrity of the blood-brain barrier. In a study of MS patients, they found that symptoms in 15 out of 26 volunteers improved. This led to further interest in the use of hyperbaric oxygen to treat MS specifically.

Since Boschetty and Cernoch’s discovery, around 14 clinical trials have been conducted. The trials have been on relatively small numbers of people and have reported conflicting results, ranging from great improvements to none at all. This has led to a dilemma: should clinicians endorse the use of hyperbaric oxygen for MS or not?

Not officially sanctioned

The clinical regulatory bodies in the US and the UK, the FDA and NICE respectively, do not feel the clinical trial evidence is strong enough to endorse the procedure, yet thousands of people in the UK and elsewhere continue to treat themselves with hyperbaric oxygen. Between 1982 and 2011, over 20,000 people with MS in the UK used hyperbaric oxygen over 2.5m times.

Multiple sclerosis is a chronic inflammatory disease of the brain. It is usually diagnosed between the ages of 20 and 40. Lesions in the brain develop as a result of inflammatory autoimmune cells crossing the blood-brain barrier and destroying the protective protein coat (myelin) that surrounds the axon of some nerve cells. Over time MS develops into a neurodegenerative disease, leading to problems with vision, bladder control and mobility.

The brain’s ability to repair some of this damage helps people with MS to feel better for a while before relapsing once more. Eventually the disease becomes chronic and the ability to repair the damage and undergo remission declines. Most conventional treatments focus on the early phases of the disease. Unfortunately, there are few treatments for the later stages of MS.

Perhaps the inability of prescribed drugs that work for all people with MS, or indeed work for some but produce unpleasant side-effects, has driven people to seek other treatments. Despite the scepticism of some doctors, many people with MS claim that hyperbaric oxygen therapy has benefits. The benefits include improvements in mobility, bladder control, pain relief and gait. However, since the treatment is transient, regular exposure to pressurised oxygen is required to sustain any benefit.

The increase in oxygen to the brain may lead to a number of effects such as speeding repair to damaged tissue, or inhibiting the ability of immune cells to cross the blood-brain barrier and cause damage. These possibilities are being investigated.

Poorly designed trials

So why are many clinicians sceptical of hyperbaric oxygen? The main reason is various MS disability-status scores are used to judge improvement. In the former clinical trials, hyperbaric oxygen was not used over a sustained periods of time (only a few weeks) and often people with irreversible damage were used, so no or very little improvement in scores was seen.

So are poorly controlled clinical trials to blame for the conflict of opinion? Probably, yes. Until we understand more at the molecular level about how oxygen under pressure can make sustained changes to various biological processes in the brain, people with MS will continue to use the treatment and the majority of the medical community will remain unconvinced of its merits.

The Conversation

Paul Eggleton, Senior lecturer in Immunology, University of Exeter

This article was originally published on The Conversation. Read the original article.