Neurological diseases cause a substantial and increasing personal, social and economic burden. Although there have been exceptions, there is increasing frustration at the limitations of learning from animal models, emphasising the importance of studying human tissue. Neuropathologists work in NHS hospitals examining samples from the brain and related tissues derived from operations (biopsies) or post mortem examinations. Their job is to identify abnormalities, make a diagnosis and try to understand how the abnormalities arise. Neuropathology has existed as a specialty in the UK for 40-50 years and, as a consequence of this work, substantial archives of diagnostically verified tissue have been established nationwide. These archives contain a wealth of tissue from a great variety of neurological conditions, including common conditions such as stroke, head injury, tumours, infections, psychiatric disorders, developmental disorders and many rare conditions, and represent an underutilised resource for research. BRAIN UK (the UK BRain Archive Information Network) networks the tissue archives of neuropathology departments based in 26 regional NHS Clinical Neuroscience Centres to form a virtual brain bank, acting as a "matchmaker" linking researchers needing tissue to the appropriate samples. Through BRAIN UK researchers can gain access to >400,000 samples from a wide range of diseases affecting the brain, spinal cord, nerve, muscle and eye. BRAIN UK has ethical approval which covers the majority of projects, saving the researchers considerable time as they would otherwise have to obtain this approval independently. Over the past 4 years BRAIN UK has supported 48 research projects in many centres around the UK and overseas. In the coming 4 years we want to continue to provide tissue to researchers from existing resources and add newly obtained samples of which >16,000 are becoming available each year. We also aim to gather the results of researchers' studies performed on tissue obtained through BRAIN UK to form a central register of findings which will benefit new researchers wanting to perform new studies on these tissue samples. Finally, we will link BRAIN UK with UK Biobank, which has 500,000 intensively studied participants from the general population, in order to learn more about the origins of neurological disease. As far as we are aware, the BRAIN UK network is unique in the world and is very economical as it makes use of tissue samples already being stored in NHS archives which would otherwise be unused and unavailable to researchers.

Digital health technologies (DHT) comprise a broad range of applications such as telehealth, wearable devices and smart-phone and tablet applications (apps). However, whilst national and international policies present ambitious plans for DHT to revolutionise healthcare, there has been little consideration of how they can be successfully integrated into healthcare systems and processes. This is important as many reports show that even well designed DHT fail to be adopted or are quickly abandoned in clinical practice, meaning that their potential to transform healthcare is lost. Stroke rehabilitation presents an ideal opportunity to use DHT to improve patient outcomes. Pressures on services mean that the amount of rehabilitation that can be directly delivered by staff, particularly for the arm, falls far short of that known to be beneficial resulting in sub-optimal outcomes for many people and reduced quality of life. With the numbers of people surviving a stroke set to double in the next 15 years, DHT provides an attractive, innovative, practical and engaging way for staff to prescribe additional rehabilitation and improve recovery for people after stroke, within current service constraints. However, DHT are not widely used in rehabilitation and the factors that influence their use in clinical practice are not known. This project seeks to identify and understand the factors that will influence the use of DHT in healthcare. It will employ this knowledge to design, implement and evaluate a DHT intervention, using rehabilitation after stroke as a case example. The project has 3 initial phases. In phase 1, the evidence considering if and how DHT are used in healthcare will be reviewed, to explore the factors influencing their use. A national survey, observations of practice, questionnaires and interviews will describe current practice and explore the behaviours and beliefs of people after stroke, rehabilitation staff and service managers about using DHT. This information will be used to develop a theory about, and framework of, the factors influencing the use of DHT in healthcare rehabilitation. In phase 2, the theory and framework will be used to co-design, create and undertake initial testing of an app and intervention to supplement routine rehabilitation for the arm after stroke with rehabilitation staff, stroke survivors and DHT developers from our in-house innovation lab. In phase 3, the initial feasibility, acceptability and costs of the app and intervention to supplement stroke rehabilitation at a single NHS trust will be evaluated. Data from interviews, questionnaires and generated by the app will investigate how it was used in practice. These findings will be used to further refine the theory and framework developed in Phase 1 and the app and intervention developed in Phase 2. In the second period of the fellowship (Phase 4), a multi-site feasibility study of the app and intervention will be conducted. The project outputs will also be used to guide and assess the use of other forms of DHT (e.g. virtual reality) in stroke rehabilitation and their transferability to support and evaluate DHT in other healthcare settings will be evaluated. This project will transform how DHT can be used in healthcare by generating a clear theory and framework and providing practical tools which detail the factors that must be considered in the design, implementation and evaluation of DHT. It will provide guidance on how patients and healthcare staff can co-design DHT and design a future trial of the effectiveness of the app and intervention. Its results will benefit technology developers and researchers by helping them design and utilise DHT to improve patient outcomes and enable healthcare organisations and policy-makers to consider the vital processes and resources required to realise the vision of a truly innovative and DHT-enabled healthcare service.

Five percent of children have disabling hearing loss. These children often experience delayed speech and language development. Although the majority of these children attend mainstream schools in the UK, only 34% achieve two A-levels (or the equivalent), compared to 55% of their hearing peers. Mild-to-moderate hearing loss (MMHL) is the most common hearing impairment in children. However, despite the effect of their hearing impairment on development it is the least understood form of hearing loss in children. This means there is an urgent need for research on this group in order to meet the goal set by the National Deaf Children's Society (the UK's biggest children's hearing charity and a partner on this project) of making sure that "by 2030, no deaf child will be left behind". Children with MMHL are prescribed auditory technology (AT) to assist them. Hearing aids are more advanced and accessible than ever, and assisted listening devices - where a talker's speech is streamed directly to the hearing aid to reduce the effects of a noisy background - are now common in classrooms. However, AT is designed based on how adults communicate: adults generally look at the person they are talking with and ask for information to be repeated when they do not hear clearly. On the other hand, children with normal hearing do not look. It is unknown if children with MMHL look at the talker while they listen. This has an impact on the effectiveness of the AT algorithms. PI Stewart has shown that children with MMHL do not have the same improvements in attention, memory and learning as adults do when using AT. This could be due to 1) the children are not wearing their AT; 2) the ATs are "too much of a good thing" and have short- or long-term effects on key hearing and listening skills (e.g. children have found that they can hear without turning to look at the talker); or 3) the ATs are not appropriate for children. To test these hypotheses, we will first systematically review children's AT usage across the UK. Second, we will gather data on the developmental impact of ATs over an 18-month period. Key hearing and listening skills including working out where a sound came from and combining audio with visual information will be assessed. Third, we will assess how children with MMHL communicate with adults and children. We will do this in a research lab in the form of a classroom where eye and head movements and brain activity can be measured. This will allow iCAT to evaluate if AT algorithms (e.g. designed for the listener to look at the talker) are appropriate for children. iCAT will work with industry, audiologists and teachers of the deaf throughout the project to ensure change towards providing child-appropriate ATs for the benefit of children with MMHL. Through the publication of white papers, iCAT will work with UK-based charities and professional bodies to create evidence-based recommendations for policy regarding the use and fitting of the AT in children with MMHL.

A major part of the diagnosis of any disease but particularly various forms of cancer, is obtained though a biopsy. This involves removing a small sample of tissue, or a few cells, from the patient. These samples, either tissue or cells are then examined by a pathologist looking down an optical microscope. In most cases the sample is stained with a combination of dyes to help gain some contrast. In most cases, based upon visual inspection of the sample a diagnosis is made. This process if far from ideal since it relies on the expertise of the clinician concerned as is subject to intra in inter observer error. Recently a number of proof of concept studies have shown that molecular spectroscopic techniques such as infrared and Raman are capable of distinguishing diseased from non diseased cells and tissue based upon the inherent chemistry contained within the cells. The UK is at the forefront of these developments but there are many hurdles that need to be overcome if this technology is to move from the proof of concept stage through the translational stage and into the clinical setting. It is the belief of the academic community that we are much more likely to overcome these hurdles if we pool our resources, bring in both industrial and clinical partners and work on these generic problems together. This application is for funding to support such a network of partners for the next three years.

This proposal brings together a critical mass of scientists from the Universities of Cardiff, Lancaster, Liverpool and Manchester and clinicians from the Christie, Lancaster and Liverpool NHS Hospital Trusts with the complementary experience and expertise to advance the understanding, diagnosis and treatment of cervical, oesophageal and prostate cancers. Cervical and prostate cancer are very common and the incidence of oesophageal is rising rapidly. There are cytology, biopsy and endoscopy techniques for extracting tissue from individuals who are at risk of developing these diseases. However the analysis of tissue by the standard techniques is problematic and subjective. There is clearly a national and international need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal. Experiments will be conducted on specimens from all three diseases using four different infrared based techniques which have complementary strengths and weaknesses: hyperspectral imaging, Raman spectroscopy, a new instrument to be developed by combining atomic force microscopy with infrared spectroscopy and a scanning near field microscope recently installed on the free electron laser on the ALICE accelerator at Daresbury. The latter instrument has recently been shown to have considerable potential for the study of oesophageal cancer yielding images which show the chemical composition with unprecedented spatial resolution (0.1 microns) while hyperspectral imaging and Raman spectroscopy have been shown by members of the team to provide high resolution spectra that provide insight into the nature of cervical and prostate cancers. The new instrument will be installed on the free electron laser at Daresbury and will yield images on the nanoscale. This combination of techniques will allow the team to probe the physical and chemical structure of these three cancers with unprecedented accuracy and this should reveal important information about their character and the chemical processes that underlie their malignant behavior. The results of the research will be of interest to the study of cancer generally particularly if it reveals feature common to all three cancers. The infrared techniques have considerable medical potential and to differing extents are on the verge of finding practical applications. Newer terahertz techniques also have significant potential in this field and may be cheaper to implement. Unfortunately the development of cheap portable terahertz diagnositic instruments is being impeded by the weakness of existing sources of terahertz radiation. By exploiting the terahertz radiation from the ALICE accelerator, which is seven orders of magnitude more intense that conventional sources, the team will advance the design of two different terahertz instruments and assess their performance against the more developed infrared techniques in cancer diagnosis. However before any of these techniques can be used by medical professionals it is essential that their strengths and limitations of are fully understood. This is one of the objectives of the proposal and it will be realised by comparing the results of each technique in studies of specimens from the three cancers that are the primary focus of the research. This will be accompanied by developing data basis and algorithms for the automated analysis of spectral and imaging data thus removing subjectivity from the diagnostic procedure. Finally the team will explore a new approach to monitoring the interactions between pathogens, pharmaceuticals and relevant cells or tissues at the cellular and subcellular level using the instruments deployed on the free electron laser at Daresbury together with Raman microscopy. If this is successful, it will be important in the longer term in developing new treatments for cancer and other diseases.