The place where you grow up can determine your health throughout your life: those born and living in disadvantaged areas are at higher risk of poor health outcomes and reduced life opportunities. Although we know that early intervention can prevent adult health inequality there is a gap in the provision and understanding of adolescent needs within integrated care systems. This project speaks to this gap: it reimagines how we co-create and design pathways to health by placing young people (age 11-16) from deprived communities in Southampton at the heart of a network of academics, civic leaders, health professionals, NGOs, cultural organisations and young people themselves. Young people tell us that culture is important to their identities and their lives. We will work together to use culture to create alternative futures. Despite being in the so-called 'affluent south' Southampton is a place of great inequality: 1 in 5 children under the age of 16 live in low-income families and a similar proportion of the population aged under eighteen live within 10% of the most deprived areas nationally. The number of looked after children in Southampton is almost a third higher than the average in England. The effects of deprivation on young people in the city create specific health challenges which become exacerbated in the adult population. Most critically these relate to alcohol consumption, mental health, and obesity. Consultations undertaken in Southampton, as part of its bid to be UK City of Culture 2025, revealed that access to culture-based health and wellbeing opportunities for young people are widely divergent across the city. It also demonstrated that young people's understanding radically differed from that of the adult population and painted a different picture of the city - its strengths, its assets and opportunities. This project places this thinking, that challenges existing approaches and creates opportunities, at the centre as it develops innovative and creative pathways to change. We will work with young people to understand what culture is to them and how understanding culture through the eyes of young people might lead to a reconceptualisation of cultural provision within an integrated care system. We will work with young people to unlock 'hidden' or unofficial cultural assets in their communities. We will better understand which cultural assets are associated with positive and negative health behaviours, and how to support 'hidden' or unauthorised cultural assets that can foster positive community outcomes. Young people will be trained as researchers and advocates and will be placed at the centre of a consortium that includes senior researchers and non-academic partners. We will bring different services and providers together to learn from young people and from each other to develop best practice and tools for using cultural engagement to improve young people's health outcomes and life chances. The project will be guided by an experienced, balanced, transdisciplinary team representing the combination of skills and expertise needed to deliver our aims. We draw on established leaders with track records of innovation from academia, the third sector, local government, practitioners, and HIoW ICS, with a shared vision to put young people at the heart of the ICS to reduce health disparities. Together we will create a community cultural asset hub that explores new pathways to health for young people through the cultures of neighbourhoods.

Microbes continually evolve antibiotic-resistant strains despite the best efforts of biomedical scientists to combat them. This is taking us towards a future where routine operations and infections become high-risk, and where we cannot produce sufficient food globally (70% of antibiotics in the USA are used in animals for food production). A new strategy is needed to combat Antimicrobial Resistance (AMR). This network will take world-leading Engineering and Physical Science (EPS) researchers and introduce them into a new Network for Antimicrobial Resistance Action (NAMRA). In a series of structured events, they will share their expertise with clinicians from the NHS, with biomedical scientists, and researchers from Health and Life Sciences. These people can tell the EPS researchers about the AMR problems that need tackling, and how any solutions must be designed to work in a real-world environment for use by healthcare workers, farmers, industry and the workplace. To help in this, the Network also includes leading researchers from Social and Human Sciences who can explain how AMR solutions must fit in with human behaviour, with Geographers who are experts in how distribution of the waters supply, and how livestock practices, affect AMR; with experts in the Legal and Ethical issues in developing new solutions to AMR for use in the wider world; and with experts in Business who research how supply chain issues affect AMR. The EPS researchers have developed many world leading technologies, from the award-winning StarStream cleaning product, to surfaces that keep clean by mimicking shark skin. Such technologies were developed for other sectors (defence, nuclear etc.) and it is vital that such expertise be translated into the fight against AMR. Within NAMRA, the inventors can access the experts who understand AMR, and access laboratories and clinics to test the step-changing solutions they collaboratively identify. In return, world-leading work by current AMR researchers can be enhanced through NAMRA contacts to: -engineer solutions; -shape them for ready adoption by healthcare workers and others; -set out the behavioural, ethical and legal framework for their adoption; and -develop the business solutions so that, rather than staying on the laboratory bench, step-changing technologies can be fashioned into products that are available across the UK, and beyond. The project begins with a 'Start-up' conference for attendees to share expertise and identify possible collaborators. Break-out sessions facilitate collaborative bids for NAMRA to fund 3-6 month projects to explore new ideas. One year in, a 'Community expansion' conference reviews the success of the collaborations to date, plans new collaborations, and invites AMR workers from across the UK, and representatives from NHS, Gov and local Gov, to discuss progress. We will hold monthly meetings on particular AMR topics for smaller sub-groups within NAMRA. We will develop a Cognitive Computing facility to identify the knowledge gaps and possible fruitful areas of collaboration, working alongside the Steering Committee which performs its own assessment. We will also work hard to ensure that, after the two years of funding for NAMRA expires, we can sustain the network. Measures to do this include offering support, training and guidance: -to ensure that interdisciplinary researchers do not 'fall into the cracks' between disciplines when publishing or applying for grants; -to team-build an exhibit for public display on AMR, covering such issues as handwashing, biofilms and the use of antibiotics; -identify and apply for sources of funding to continue their collaborations (incl. peer-reviewing proposals); -to communicate their work to the public, via websites, school visits, Science Fairs; -to the next generation of leaders in AMR. The project ends with a 'Way Ahead' conference to ensure the good work continues after this funding ceases.

Digital Micromirror Devices (DMDs) are the heart of the image-projection technology used in the modern cinema projectors. They are a 2D array of several million, micro-sized, computer-controllable mirrors, where each mirror can flip on its axis many thousands of times per second. When combined with a RGB light source, such as in a cinema, the device enables the projection of full-colour videos onto a screen. However, in recent years this projection technology has moved out of the cinema and into laboratories across the world, where it is assisting scientists in many research fields. At the Optoelectronics Research Centre, at the University of Southampton, scientists have been using this DMD technology to generate micron-sized intricate patterns of laser light, for the development of a range of novel subtractive (removing material) and additive (adding material) laser-based manufacturing processes. In this 5-year project, the team will be working with a wide range of industrial and academic partners, who see the potential for new and exciting manufacturing processes, as summarised below: SPI Lasers, a UK fibre laser company: A major advantage of using DMDs for shaping a laser beam is the extremely high speed at which light patterns can be generated, updated and modified. The team will be combining fibre laser technology with DMD technology to enable extremely high-repetition-rate beam shape and energy control, for applications in a wide range of manufacturing areas including the marking of high-value objects. M-Solv, a UK laser-integrator: Here, the team will be testing and optimising their technology using a wide range of industrial manufacturing lasers, and will develop a range of novel additive manufacturing processes for the micro-scale. The outcome will be additional manufacturing capability for UK companies. University Hospital Southampton: Recent scientific results have shown the ability to control the specialisation of human stem cells (e.g. to bone or to muscle) via intricately designed 2D surface structures. Working with Prof. Richard Oreffo, a founder of this field, the team will be using their technique to produce a range of bespoke surface-textured substrates that will enable biologists to further understand and control stem-cell specialisation for applications in regenerative medicine. University of Southampton: Metamaterials are a family of materials that offer amazingly unusual properties, such as the ability to bend light (for use as invisibility cloaks) or even slow it right down. However, scientists have yet to develop a cost-effective method for making such devices on centimetre or larger size-scales. The team will be investigating whether the DMDs combined with high-repetition-rate lasers can speed up the process and enable cost-effective manufacturing of cm-sized devices. Oxsensis, a UK company that develops sensors for extreme environments: The team intends to develop new manufacturing processes that will enable a new range of sensors for applications in industries such as Aerospace, Power Generation, and Oil and Gas. Specifically, the team will be using their recently demonstrated ability to laser-machine very accurately and rapidly in diamond, in order to develop new techniques for making sensors in a range of difficult-to-machine materials.

Computational biomedicine offers many avenues for taking full advantage of emerging exascale computing resources and, as such, will provide a wealth of benefits as a use-case within the wider ExCALIBUR initiative. These benefits will be realised not just via the medical problems we elucidate but also through the technical developments we implement to enhance the underlying algorithmic performance and workflows supporting their deployment. Without the technical capacity to effectively utilise resources at such unprecedented scale - either in large monolithic simulations spread over the equivalent of many hundreds of thousands of cores, in coupled code settings, or being launched as massive sets of tasks to enhance drug discovery or probe a human population - the advances in hardware performance and scale cannot be fully capitalised on. Our project will seek to identify solutions to these challenges and communicate them throughout the ExCALIBUR community, bringing the field of computational biomedicine and its community of practitioners to join those disciplines that make regular use of high-performance computing and are also seeking to reach the exascale. In this project, we will be deploying applications in three key areas of computational biomedicine: molecular medicine, vascular modelling and cardiac simulation. This scope and diversity of our use cases mean that we shall appeal strongly to the biomedical community at large. We shall demonstrate how to develop and deploy applications on emerging exascale machines to achieve increasingly high-fidelity descriptions of the human body in health and disease. In the field of molecular modelling, we shall develop and deploy complex workflows built from a combination of machine learning and physics-based methods to accelerate the preclinical drug discovery pipeline and for personalised drug treatment. These methods will enable us to develop highly selective small molecule therapeutics for cell surface receptors that mediate key physiological responses. Our vascular studies will utilise a combination of 1D, 3D models and machine learning to examine blood flow through complex, personalised arterial and venous structures. We will seek to utilise these in the identification of risk factors in clinical applications such as aneurysm rupture and for the management of ischaemic stroke. Within the cardiac simulation domain, a new GPU accelerated code will be utilised to perform multiscale cardiac electrophysiology simulations. By running large populations based on large clinical datasets such as UK Biobank, we can identify individual at elevated risk of various forms of heart disease. Coupling heart models to simulations of vascular blood flow will allow us to assess how problems which arise in one part of the body (such as the heart) can cause pathologies on remote regions. This exchange of knowledge will form a key component of CompBioMedX. Through this focussed effort, we will engage with the broader ExCALIBUR initiative to ensure that we take advantage of the efforts already underway within the community and in return reciprocate through the advances made with our use case. Many biomedical experts remain unfamiliar with high-performance computing and need to be better informed of its advantages and capabilities. We shall engage pro-actively with medical students early in their career to illustrate the benefits of using modelling and supercomputers and encourage them to exploit them in their own medical research. We shall engage in a similar manner with undergraduate biosciences students to establish a culture and practice of using computational methods to inform the experimental work underpinning the basic science that is the first step in the translational pathway from bench to bedside.

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