One in four of us will suffer from some form of mental health problem in a given year. For the majority of us, this will be some form of anxiety or stress related problem. Some people's anxiety is so crippling that they end up housebound. Anxiety costs the UK economy over £14 billion a year. We currently have effective clinical treatments, both psychological (i.e. therapy) and pharmacological (i.e. medication), that can treat anxiety. However, we are not currently able to effectively target these treatments to people who will respond. In fact, for most people, the first treatment that they try will not work. Even more worrying is that for up to 25% of sufferers; none of our current treatments will work. There are at least two reasons that we have these problems targeting treatments: I) We do not know how our current treatments work at a biological level II) We do not know how debilitating feelings of anxiety emerge from the underlying biology. Without a better understanding of both of these issues we will not improve our ability to target treatments. This fellowship therefore seeks to improve our understanding of the biological basis of anxiety symptoms and treatments. It focuses on psychological treatments and aims to better understand 1) the neural circuitry by which psychological treatment works; 2) develop new psychological treatments; and 3) better refine our understanding of the biological bases of anxiety diagnosis. Specifically: 1) Neural Circuitry: Over the last decade, I have identified a brain circuit which drives feelings of anxiety but we do not know if it changes following treatment. In this project I will scan the brains of anxious people undergoing psychological treatment for anxiety and compare them to anxious people who are not. If we show that this same circuit is important for treatment response, it will enable us to better target treatments to individuals, and reduce the number of people who try treatments that do not work for them. 2) Treatments: In parallel with this I will attempt to develop a new computerised treatment for anxiety. This is possible because my advances in a new field known as computational psychiatry have given us tools that provide better insight into the computational process of the brain, and how they change in anxiety disorders. I will therefore develop a computerised training procedure that targets these computational processes and test it in a treatment study. If this works, it will provide a quick and cost effective treatment that could be delivered by smartphones and ultimately reduce the number of individuals suffering from anxiety. 3) Diagnosis: Finally, I will try to improve our understanding of how debilitating feelings of anxiety emerge in the first place. It is increasingly clear that our current diagnoses, which are based on symptom checklists, do not reflect truly separate biological categories. I will therefore search for 'trans-diagnostic' dimensions that drive anxiety but which cut across our current categories. I shall do this by getting thousands of people to complete a simple psychological task online that I have previously linked to debilitating anxiety. In addition, we will collect a wide range of other psychological tasks and questionnaires from these people. Applying state-of-the-art statistical methods to this 'big data' will enable us to identify trans-diagnostic dimensions that drive anxiety symptoms. In the long term these new trans-diagnostic dimensions will improve our ability to determine the biological factors driving symptoms and hence help us predict treatment response and develop new treatments. In sum, I will combine my unique inter-disciplinary skill-set, with my breakthroughs in delineating the neural and computational basis of anxiety, to develop new and more effective clinical tools for anxiety diagnosis and treatment, with the ultimate goal of improving the quality of life for millions of sufferers.

DPUK is a public-private partnership to accelerate the development of new treatments for dementia. Since inception (2014) DPUK has increased the UK capacity for dementia research through infrastructure development and strategic data collection, leveraging a further £74.4m for dementia research. The second phase of DPUK (DPUK2) focuses on developing UK capacity for dementia experimental medicine. A major challenge in developing new treatments is understanding the mechanisms through which a drug might operate. This involves precision studies where individuals of known vulnerability to specific causes of dementia are recruited to studies of cause-specific mechanistic pathways. These studies are very difficult to do as they require detailed assessment of volunteers before the study begins and standardising all the procedures in centres across the UK. These studies are also high risk in that there is no guarantee of success. DPUK2 addresses these issues head-on at two levels. First it uses the UK's rich legacy in population cohort studies to identify suitable volunteers by using and enhancing existing cohort data. Second it creates a pre-competitive environment that brings together industry, academic and third-sector entities into partnership. This not only shares the costs and risks of experimental medicine (EM) studies, it also shares the benefits amongst a wider spread of stakeholders, each able to exploit the findings. DPUK2 does this through 3 inter-dependent work-streams. 1. The Data Portal (DP): The DP is a world leading end-to-end dementia focused data management solution. It enables large and complex datasets to be accessed remotely from around the globe without compromising data security. The DP is being developed in partnership with Health Data Research UK (HDR UK) so that we can maximise the data available to dementia research. The DP is used to manage all the data and information systems necessary for conducting precision studies. It brings large and complex datasets together in order to test new ideas; it manages personal information securely to enable recruitment to precision studies; it manages many types of data so that genetics, brain imaging, cognitive performance; and questionnaire data can all be analysed together. 2. The Trials Delivery Framework (TDF): The TDF is the vehicle that enables the DPUK2 experimental medicine programme to be efficient. The TDF organises our Clinical Studies Register (CSR) through which cohort members can volunteer for experimental medicine studies. The CSR allows us to contact members to enrich their data in terms of background information, cognitive testing, and where necessary genetics. As part of the CSR, and in partnership with the Alzheimer's Society, we have a PPI programme to understand what best practice is in terms if recruitment to experimental medicine studies. The TDF also enables us to identify centres of excellence across the UK for conducting experimental studies rigorously. This not only assures data quality, but also means that volunteers do not have to travel too far to participate. 3. The EM Incubator: The incubator is where our partners meet to plan and execute the experimental medicine programme. It has three themes; the first is Vascular Health. This is important because so many factors that affect the heart also affect the brain. If any area is likely to have drugs that already exist and could be re-purposed for dementia, this is it.The second theme is Synaptic Health. Here we investigate factors that affect the loss of neuron synapses. This is important because unlike neurons, synapses (the connections between neurons), can be generated, which is critical to learning and maintaining memory. The third area is Neuroimmunology. This is important as inflammation is a systemic problem that is known to affect the brain and might have systemic solutions, and so represents a promising area for new treatments.

Society is battling with an explosion of health conditions that need long-term management. These chronic conditions occur at all ages: UK children have some of the world's highest levels of both asthma and type 1 diabetes and, with a third of the UK's school children leaving primary education obese, there are huge concerns over type 2 diabetes at all ages; in any year, working age men and women in the UK have a 12% chance of a diagnosed mental health issue such as anxiety, depression and post-natal depression; conditions including dementia, Parkinson's disease and frailty are rapidly increasing in later years. Low-cost, connected, digital technologies are increasingly seen as vital to the understanding, prevention, diagnosis and management of these conditions for months and years in the community. These digital technologies, such as smartphone apps, wearables, blood sugar monitors - and a near future of Internet of Things (IoT) devices such as smart home systems (e.g. Echo), smart meters and connected appliances - offer an unprecedented opportunity to monitor a patient's condition within their community. With the data processed by artificial intelligence they will deliver decision support to health and care professionals; predict or detect a patient's symptoms worsening; support independent living; deliver behavioural and even pharmaceutical interventions; and allow the efficacy of treatments to be monitored. This cannot be business as usual for doctoral education since a digital health technology is likely to require a highly multidisciplinary understanding of technologies spanning software engineering, microelectronics, data communication, signal processing, machine learning and visualisation. Achieving actual patient benefit requires user-centred/driven design, a broad understanding of health and care, psychology, physiology, ethics, regulation, health economics and the design of clinical trials. To meet the challenge and seize the opportunity, the UK needs to nurture leadership that will span this hugely multidisciplinary space - combining technological depth with broad appreciation of the health landscape; empathy with the patient's needs with an eye to business models that underpin adoption; ambition to accelerate innovation with a principled commitment to ethics, inclusivity, regulation, data security and privacy. The opportunity and the challenge for this Centre for Doctoral Training (CDT) in Digital Health and Care is to be bigger than the sum of its parts; to physically co-locate a cohort of students from Engineering & Computer Sciences and Health & Life Sciences; to bridge the disciplinary gaps, work with key external partners, foster better understandings and activate peer-to-peer learning within the cohort itself. Bristol is the perfect place to train future leaders at this disciplinary interface, building on £30M of digital health research at the University since 2013. Our proposed CDT will develop team-players with the skills to work effectively with experts from other disciplines, with patients and with the public. In a space where issues of trust, privacy, transparency, accountability and inclusion are absolutely fundamental, the CDT will not only embrace Responsible Innovation but influence and lead best practice nationally and internationally. The CDT will build on a variety of established relationships; with small and medium sized businesses, technology companies, big pharmaceutical companies, charities, universities, one of the UK's largest public science centres (WeTheCurious), Bristol City Council, and with the public. This CDT is therefore envisaged as a multidisciplinary community of students and academics that will create exciting research projects and will build networks of individuals across academia, industry and the NHS at all levels. It will sow the seeds of future collaborative research and of commercialisation activities.