This project is trying to find out about the experiences of patients and healthcare professionals in 15 Latin American countries who are part of a study (Latin SEQ) that is offering a type of genetic testing called whole exome sequencing (WES) to diagnose inherited muscle diseases. This type of test can also identify if a patient has other genetic conditions or risks of disease that have nothing to do with their muscle disease symptoms (because WES does not just look at muscle disease genes). The test may diagnose conditions that patients and their doctors do not expect and they are not prepared for. WES can also come up with uncertain answers that are difficult to interpret. There are many potential benefits of having a genetic diagnosis for muscle diseases. A diagnosis can help to tailor treatment or supportive care, it can help families to understand why their relative has a disease and answer questions that they may have asked for a long time, it can give other family members genetic information that they might use for their medical care or prenatal options for their future family. There are also some downsides and sometimes patients' can struggle to come to terms with a genetic diagnosis for many reasons. Parents may feel guilty once they know their child has inherited a condition or disease from them. A genetic diagnosis can cause family upset when family members, who may be at risk of the genetic condition, do not want to know. In some cultures, people may feel stigmatised by the information. It can sometimes affect financial arrangements like insurances and some career opportunities. These are issues, which a genetic counsellor would usually discuss with patients before testing. In many of the 15 LA countries, there is no genetic counselling available and healthcare professionals in the muscle disease service will inform patients about WES and the possible genetics of their disease and/or any unexpected findings. In addition, in LA countries access to supportive care services may vary. Some tailored therapies may not be available even when a genetic diagnosis is found. Prenatal testing may not be available because of legal, religious or cultural restrictions. In the UK, although we have genetic counselling, WES is also beginning to be offered to patients by doctors who are not geneticists. We can therefore learn from the experiences of healthcare professionals and patients in Latin America who do not have genetic counselling services. The findings of this study, when shared with the participating centres, can also help to support the development of genetic services in the Latin American countries. The study aims to evaluate patients', families' and HCP's experiences of: 1) Receiving and giving a genetic diagnosis, 2) How and if there are changes to patient care following WES 3)Pre-natal testing opportunities and uptake 4) Communicating genetic information within families 5) Receiving and giving unexpected findings 6) Dealing with variants of uncertain significance 7)Cultural contexts. The study objectives are to develop educational input and resources, highlight areas of good practice as measured against UK genetic counselling standards, share findings with LA partners to grow their genetics services and improve patient outcomes, share findings with Health Education England and Genome England to inform UK service development. The project will generate new knowledge about delivering effective genetic counselling to improve patient outcomes in Latin America and in the UK.

Seeing involves a complex set of processes that allow us to extract information from the physical world. As you read this, an image of the text is formed by the optical elements of your eye and this image is sensed by the light-sensitive cells that tile your retina. Neurons in your retina and brain process this sensory input, ultimately allowing you to extract meaning from the text. This happens in a fraction of second between jump-like movements of your eyes that shift your gaze across the text. Even during the periods when we think our eyes are still, they continually make microscopic movements that are fundamental to seeing anything at all. Disruption to the sensory input, such as by retinal degeneration or refractive errors, places a fundamental limit on the information available to the visual system. Visual disorders significantly impact on an individual's health, wellbeing and quality of life. Visual impairments in childhood can affect school performance, and in the elderly they can severely restrict everyday activities and affect independence. Visual disorders have their effect at many levels, from changes in the eye, to deficits in visual and cognitive processing, and alterations to the efficient movement of the eyes. Visual disorders are best tackled with a cross-disciplinary approach, working across these levels. Adaptive optics is a powerful technique originally developed for astronomy that has revolutionised the study of the eye, allowing human vision to be characterised with extraordinary precision. By correcting for optical distortions, which are present in every eye, adaptive optics allows imaging of individual cells in the living human eye and provides exciting new capabilities for tracking the tiniest of eye movements with unprecedented accuracy. By manipulating the optical distortions of the eye, adaptive optics also allows investigation of the impact of refractive errors on sight. I will take an interdisciplinary approach, developing adaptive optics techniques in combination with precise experiments in human vision to understand how the visual system processes information and how this is disrupted by visual impairments. I will address these fundamental questions through targeted investigation of two leading causes of visual impairment: 1. Age-related macular degeneration affects around 600,000 people in the UK, severely affecting sight by causing loss of central vision - imagine the difficulty of having a blind spot follow wherever you look. Being incurable, treatments aim to preserve remaining sight and so early detection is crucial. I will investigate the relationship between degeneration in the retina, eye movements and visual function. This will inform interventions, such as visual aids and eye movement training, to make the best use of patients' remaining sight. The high precision of adaptive optics will allow me to make very sensitive measures of alterations to eye movements. I will look for characteristic changes that could be screened for, leading to very early detection of disease. 2. Refractive errors (e.g. myopia and astigmatism) affect around 1 in 7 children in the UK. Even in the healthy eye, there are more complex high-order optical distortions that are not correctable with spectacles. Optical distortions impair visual acuity - such as the ability to identify letters on a chart - but can cause further problems in more cognitively demanding tasks, such as reading. Our society makes heavy use of text to convey important information. My research will use adaptive optics to investigate how optical distortions impact on reading, for example by impairing recognition or disrupting eye movements. This will enable better accessibility to information, through improved visual aids or eye guidance training, or through designing fonts for educational materials that are more robust to refractive errors.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The emergence and re-emergence of infectious diseases is one of the greatest threats to human health. By their very nature, outbreaks of infectious disease can spread rapidly, causing enormous losses to health and livelihood. For example, an estimated 35-million people are HIV-infected, antibiotic resistant pathogens such as MRSA are a major global public health problem and pandemic influenza is rated as the greatest national risk on the UK government risk register (Cabinet Office 'National Risk Register for Civil Emergencies 2012 Edition'). Early diagnosis plays a vital role in the treatment, care and prevention of infectious diseases. However worldwide, many infections remain undiagnosed and untreated or are diagnosed at the late stage due to poor diagnostic tools, resulting in on-going transmission of serious infections or delay in the identification of emerging threats, leading to major human and economic consequences for millions of people. Our vision is to establish an EPSRC Interdisciplinary Research Centre to create a new generation of early-warning sensing systems to diagnose, monitor & prevent the spread of infectious diseases. This large scale collaboration will bring together scientists, engineers and computer scientists from University College London, Imperial College, London School of Hygiene and Tropical Medicine and the University of Newcastle together with NHS stakeholders, the Health Protection Agency and industry partners. Working across and beyond traditional research boundaries, the IRC will pioneer innovative nano-enabled mobile diagnostic tests which can be used in GP surgeries, community settings and developing countries, linked to smart digital-surveillance systems which search for information on the web to detect early indicators of diseases. The tremendous expansion in mobile phone technology with an estimated 6 billion users worldwide, provides new opportunities for point-of-care diagnostics with inbuilt capacity to securely transmit results to public healthcare systems. The challenge is to create robust multimarker sensor platforms that can diagnose early infections with high sensitivity and specificity. Our strategy will seamlessly integrate the scientific excellence underpinning recent breakthroughs by our team in diverse areas of biomarker discovery, capture coatings, nanoparticles, nanopatterning, sensor systems, wireless connectivity, data mining and health economic analysis of diagnostics. Moreover we will explore innovative new strategies to search for early indicators of infection (herein we coin the phrase "e-markers") by searching through millions of web-accessible information sources including Google, Facebook and Twitter to identify outbreaks even from people who do not attend clinics or from geographical regions that are invisible to traditional public health efforts. By providing doctors, community workers and public health organisations with real-time, geographically-linked information about emerging infections which will be visualised on a "dashboard" display, we will support more rapid, stratified, integrated evidence-based interventions, benefitting individuals and populations. Our disruptive early warning sensing capabilities will bring major human and economic benefits to the NHS and global healthcare systems. The ultimate beneficiaries will be patients since early diagnosis will empower them to gain faster access to better treatments, helping to reduce suffering and risk of death. Society will benefit by preventing the onwards spread of infection by people who are unaware of their infection and preserve the effectiveness of precious antimicrobial medicines for future generations. The NHS and healthcare systems will benefit by simplifying patient pathways allowing tests and results to be given in a single visit and so provide a more cost-effective solution of community based care. Our technologies will also provide new commercial opportunities for British industry.

Biofilms are microbial cells embedded within a self-secreted extracellular polymeric substance (EPS) matrix which adhere to substrates. Biofilms are central to some of the most urgent global challenges across diverse fields of application, from medicine to industry to the environment and exert considerable economic and social impact. For example, catheter-associated urinary tract infections (CAUTI) in hospitals has been estimated to cause additional health-care costs of £1-2.5 billion in the United Kingdom alone (Ramstedt et al, Macromolec. Biosci. 19, 2019) and to cause over 2000 deaths per year (Feneley et al, J. Med. Eng. Technol. 39, 2015). To combat biofilm growth on surfaces, chemical-based approaches using immobilization of antimicrobial agents (i.e. antibiotics, silver particles) can trigger antimicrobial resistance (AMR), but are often not sustainable. Alternatively, bio-inspired nanostructured surfaces (e.g. cicada wing, lotus leaf) can be used, but their effects often may not last. A recent innovation in creating slippery surfaces has been inspired by the slippery surface strategy of the carnivorous Nepenthes pitcher plant. These slippery surfaces involve the impregnation of a porous or textured solid surface with a liquid lubricant locked-in to the structure. Such liquid surfaces have been shown to have promise as antifouling surfaces by inhibiting the direct access to the solid surface for biofilm attachment, adhesion and growth. However, the antibiofilm performance of these new liquid surfaces under flow conditions remains a concern due to flow-induced depletion of lubricant. Here we propose a novel anti-biofilm surface by creating permanently bound slippery liquid-like solid surfaces. Success would transform our understanding about bacteria living on surfaces and open-up new design paradigms for the development of next generation antibiofilm surfaces for a wide range of applications (e.g. biomedical devices and ship hulls). To enable the successful delivery of this project, it requires us to combine cross-disciplinary skills ranging from materials chemistry, physical and chemical characterisations of materials surfaces, nanomechanics, microbiology, biomechanics, to computational mechanics. The project objectives well align with EPSRC Healthcare Technologies Grand Challenges, addressing the topics of controlling the amount of physical intervention required, optimizing treatment, and transforming community health and care. In parallel, we shall contribute to the advancement of Cross-Cutting Research Capabilities (e.g. advanced materials, future manufacturing technologies and sustainable design of medical devices) that are essential for delivering these Grand Challenges. In particular, this research will employ nanomechanical tests to determine bacteria adhesion and microfluidics techniques for biofilm characterisation, which enables us to create novel approaches in computational engineering through the formulation and validation of sophisticated numerical models of bacteria attachment and biofilm mechanics.