Gene therapies rely on engineered virus carriers as vehicles for the delivery of synthetic genes that allow correction of disease-altered changes in multiple organs of the human body. Viruses exploited in gene therapy approaches have been modified to remove harmful properties and carry the therapeutic gene of interest. Multiple gene therapy programmes are currently undertaken in research laboratories using relatively small-scale production of viruses which enables optimisation of the doses and administration routes as well as testing for the safety and therapeutic efficacy of interventions in animal models of disease. However, facilities required for the production of large quantities of clinical-grade viruses of consistent quality-controlled GMP grade are rare in the UK. Thus, it can easily take several years before clinical trials can be conducted. Currently, existing facilities cannot meet the escalating demand of academically-led research needs for clinical-grade virus carriers. This is significantly obstructing numerous UK-funded world-leading disease-modifying discoveries to be translated into clinical trials for human benefit. The lack of suitable GMP facilities seriously hinders the development of much-needed novel effective treatments for multiple incurable diseases which cannot be treated by conventional drug compounds. We propose to address the manufacturing shortage by creating a Gene Therapy Innovation and Manufacturing Centre (GTIMC) which includes provision of a new state-of-the-art GMP manufacturing facility to support gene therapy projects emerging from UK universities. GTIMC will also support the development of improved viral vectors, improved yield from the manufacturing process and will also provide essential regulatory and training support. Moreover, the GTIMC hub will allow new training and high-skilled employment opportunities through the ShefVec facility itself, and future start-up companies.

The Circular Economy (CE) is gaining mainstream attention, but not in all sectors. The linear model, from cradle to grave, still prevails for small Medical Devices (MDs). The perception of cross contamination dominates management and processing practice after first use, but studies show that only a minority of healthcare waste is infectious. Potential innovations in product design, materials, procedure management and post-use processing offer effective infection control to enable a far higher percentage of material to enter additional cycles of functionality beyond first use. With savings from reprocessing reported at around 50%, NHS costs would reduce by hundreds of millions of pounds if such circular use of resources is fully implemented. Additional cycles may be in closed loops of MD functionality, remaining legally compliant, or open loops, where material is used in other sectors. This project aims to develop these technical and non-technical solutions and bring them together in a coherent 'whole system' to demonstrate operation of the Circular Economy for four representative small MDs. This will require a multidisciplinary approach to utilise the expertise of product designers, manufacturers, clinical staff, waste management companies and waste processors. Wider adoption will need the engagement of professionals in health service procurement and intermediary organisations from the commercial and non-profit sectors, such as trade bodies, consultancies and health NGOs. The project will last 2.5 years. Based on a well-defined understanding of the problem, it will start with stakeholder workshops to conduct a deep dive on the planned innovations in product design (including materials) and reprocessing technologies as well as operational and management systems. Separate but coordinated work tracks and teams will then develop innovations in these fields and produce full specifications. These will then be brought together in proof-of-concept experiments to evaluate the whole circular system. The engineering innovations related to adapted or novel small MDs designs, materials and material selection methods, and reprocessing technologies (re-use, remanufacturing or recycling) will be encapsulated in targeted CE specifications for four reference products as well as more abstracted CE guidelines for application to each product category. The specifications for each part of the circular system and the evaluation results will be published in a variety of media and be available for project partners and others to develop into large scale systems. The project will expand knowledge of the principles of effective Circular Economy systems in a part of the healthcare sector and integrate learning from the few previous waste management projects on specific medical devices into a 'whole system' approach. In this way we hope to significantly influence the development of a UK circular Economy for small medical devices.

Hospital buildings are critical for supporting effective patient treatment. There is strong evidence that the design of patient environments influences well-being and comfort, recovery rates and can both cause and control transmission of infections, particularly those with an airborne component. Recent surveillance in England estimates 6% patients a year contract an infection while in hospital, which with hospital admissions of 15.9 million, totals almost 1 million people. Around 20% of infections are thought to be directly related to the environment. Hospital buildings have not progressed at the same rate as medical advances and many clinicians are treating patients in sub-optimal conditions. In addition recent scrutiny of healthcare buildings has been dominated by a focus on their energy usage, and there is increasing concern that decisions are made on energy and cost efficiency grounds without proper understanding of the risk to patients. This is counter-productive; efficiency savings in buildings leads to increased risks and hence costs in clinical delivery. With the NHS commitment to reduce recurrent revenue costs in supporting reduction of the national £22bn funding shortfall, it is essential that buildings are considered holistically and that the influence on patient outcomes is properly factored in. A major barrier to delivering good patient environments is having usable tools to assess risks and adapt the environment and operations in a responsive manner. Current tools for designing and operating healthcare buildings and selecting technology are good at modelling energy, but are very limited from a health and infection control perspective. Our previous research developed new methods for modelling hospital environments and their influence on infection risk. In this project we aim to build on these approaches to develop and test novel computational based tools to assess, monitor and control real patient environments in hospitals for infection control, comfort and well-being. We will develop and couple models of physical, environmental, microbial and human parameters together with environmental sensor data to build new tools to dynamically model hospital environments. These will focus on addressing challenges with existing wards which are often constrained by the current building design and in many cases are naturally ventilated via opening windows. We will build a system that links sensors with a real-time fluid dynamics simulation model to enable live monitoring of environmental conditions and allow predictions to be made for rapid adaption. This will inform and control aspects like window opening, heaters and additional cooling to optimise the patient environment for comfort and air quality parameters. Alongside this we will develop a quantitative pathogen exposure model that can enable comparison of the relative risk of air and surface transmission and likely effectiveness of different design and infection control strategies. This tool will support decision making and scenario testing, as well as provide a valuable interactive training tool to demonstrate the interactions between pathogens, people and the physical environment. The project has significant interaction with clinicians who manage complex ward environments and a wide range of patients, and expertise in industry in the design, specification and operation of hospitals. We will develop and test our approaches on real wards to understand their challenges, measure variability in conditions and evaluate how and where our models can best be used to inform practice. By working closely with industry partners we will understand how our pilot tools can be deployed in design and estates management and where they may inform guidance and governance. The project will deliver new risk based ways of assessing healthcare environments that support decisions, training, design and future guidance.

Mobility, wellbeing and the built environment: Wellbeing in later life is linked to the maintenance of independence, physical mobility itself and the sense of being able to get about. Mobility is vital for accessing services, resources and facilities, for social participation, and for avoiding loneliness. Thus mobility has been described more broadly as 'engagement with the world'. The design of the built environment has a key role to play in enabling - or frustrating - mobility. Thus appropriate design or redesign of the built environment can expand horizons and support wellbeing. However, this project focuses on complements or alternatives to physical design or redesign of the built environment. Design and adaptation are time and resource intensive. Many well-understood mobility barriers remain in place because of budget constraints. Design of the built environment is just one the determinants of mobility and wellbeing. Any one environment cannot meet all needs at once, and needs can vary even for an individual, as people pass through key physical and social transitions which may alter mobility and wellbeing. Based on participatory research, this project aims to create a suite of options and tools which may be able to meet contrasting needs, support mobility and wellbeing, and do so more quickly and affordably than adapting the built environment. The research aims to: 1) Explore mobility and wellbeing for older people going through critical but common life transitions; 2) Investigate and address variation and contradictions in needs of different groups of older people (and even for single individuals over time), and between different built environment agendas; and 3) To co-create practical tools which can act as complements or alternatives to redesign of the built environment. After a foundation stage the work will commence with interviews with national experts and stakeholders. We will select three contrasting local areas in which to base the rest of the research, and interview c15 local stakeholders in each area. We will then start a pioneering quarterly tracking study of mobility and wellbeing, working with c120 older people in the three sites who are experiencing critical but common life transitions such as losing a driving license, losing a partner, or becoming a carer. These transitions are often seen as key points for deterioration in mobility and wellbeing, and as key points for support and intervention. We will then work with a series of small groups of older people in workshops and co-design sessions, to explore the potential for interventions as alternatives and complements to promoting mobility and wellbeing via redesign. Each will involve a series of day-long meetings between researchers and older people, over about a year. One set of workshops will explore how well 'crowdsourcing' and Participatory Geographical Information Systems can add to and collate information about mobility wants and needs and barriers. Another will involve older people with varying interests in relation to the built environment, to explore conflicts and the potential for consensus on some issues. There will be co-design workshops with older people to explore mobile technologies based on SmartPhones, to help people avoid key blockages to mobility in particular areas. Other workshops will work with mobility scooter users, and manufacturers and those whose mobility may be threatened by scooters, to explore the feasibility of adapting scooters to reduce problems. The impact of participation itself will be tracked. Project outputs will include: a project website, accessible annual interim and summative reports to project stakeholders and others, a summative report, articles for academic journals across team member disciplines, trade press articles for relevant professionals, potentially video or new media, a local stakeholder and older person conference and national 'Roadshow', as well as other dissemination events.

Up to 1 in 5 patients hospitalised by COVID-19 have evidence of heart muscle injury as measured from a blood test. This is associated with a high death rate. Using an MRI scan of the heart we aim to investigate how often, and in what way, the heart becomes damaged, and how the heart recovers 6 months later. We need to know how heart muscle damage and recovery is affected by age, sex, ethnicity and other medical conditions (such as diabetes, high blood pressure, heart disease and narrowing of blood vessels), as these are also known to be associated with high death rates. We also want to see if we can improve the diagnosis of viral heart damage from a simple ECG, which may save patients having invasive heart tests which can be uncomfortable, are expensive and carry a small risk of serious complications and may put healthcare staff at increased risk of exposure to COVID-19.