This study will assess the impact on mental health of restricted access to arts and culture in a specific city region, and track, enable and enhance the value of innovation in arts provision in mitigating associated harms. Liverpool has one of the richest concentrations of culture in the UK, boasting the largest clustering of museums and galleries outside London. Cultural capital is critical to the city region's economy, contributing c10% (Culture Liverpool,2019). The city also has a pioneering history of harnessing arts for mental health care through partnerships between culture and health providers. Building on the University of Liverpool's strong alliance with organisations across these sectors, this project brings together an interdisciplinary team of arts and mental health researchers to devise and conduct, in consultation with cultural and health bodies, two surveys. Survey 1 (online interviews) will target 20 arts organisations (10 civic institutions, 10 community arts programmes, representing 'elite' and 'popular' arts) to capture (i)the impact of COVID-19 on public access to arts provision (including those who usually access the arts through formal healthcare routes) and on audience/beneficiary change over time (legacy losses and potential gains) (ii)the success of alternative (e.g. online/digital) modes of provision by arts organisations in reaching and communicating with established and/or new audiences. Survey 2 (online questionnaire and supplementary online/telephone interviews) will target c300 arts' audiences/beneficiaries to capture (i)the impact on mental health of restricted/non-existent access to usual provision (ii)the perceived value and accessibility of alternative arts provision and the latter's impact on mental health/wellbeing.

This proposal will develop novel silicone oil tamponades providing controlled drug delivery to the back of the eye to prevent proliferative vitreoretinopathy, a blinding condition with no gold standard for treatment. Proliferative vitreoretinopathy (PVR) is a disease that can develop following retinal detachment. It is the primary cause of failure following surgery to re-attach the retina and often results in poor visual outcome. Despite many strategies, there has been no improvement in outcome over the last 20 years and these patients can lose their sight. Complicated retinal detachments require silicone oil to re-attach the retina. Effective pharmacological treatment of PVR requires controlled, sustained release of a drug. A key challenge is that certain drugs that could be used to control PVR cannot dissolve in the oil. If injected into the eye they accumulate around the oil and cause toxicity to the retina. Furthermore, repeat injections increase the risk of complications. Thus, an entirely new approach is required. This proposal uniquely aims to develop a silicone oil tamponade with a dual role, firstly to act as a tamponade agent and secondly to be a novel drug-delivery system. It will use non-steroidal anti-inflammatory drugs (NSAIDS), which have the potential to address the inflammatory as well as the proliferative stages of PVR. The project will use novel chemical techniques to bind drugs to the silicone oil so that they will be released in a sustained, controlled manner. Preliminary data has demonstrated that drugs can be bound to silicone oil, and that the release profile of the drug can be changed by varying the blend of the oil. An in vitro model of the oil-filled eye, incorporating the flow of aqueous out of the eye, has also been developed. This will allow studies of drug clearance from the eye. This programme proposes the combined development and in vitro biological evaluation of a new drug delivery system, focussed on NSAIDS, with additional drug candidates for risk mitigation. Furthermore, it will develop a new approach to biological evaluation that will make future animal trials more efficient. Drugs will be bound to silicone oil using several strategies and release studies undertaken. The conditions required to release the drug under clinically relevant conditions, at a concentration identified as being non-toxic but effective at controlling cell behaviour, will be identified. Drug-oil products will also be assessed in a variety of laboratory models to assess how effective they are at controlling PVR-like behaviour, using techniques that are well-established in the host laboratories. The testing will be iterative, with results being fed back to inform the development of the prototype oils. The physical and optical properties of the drug-oil products, as well as suitable methods for sterilisation, will also be assessed. Development of new methods for drug delivery could have significant benefits for industry and the healthcare system. Furthermore, the repurposing of existing drugs for treatment of PVR would speed the translation of treatments to the clinic and represent a new stream of revenue for these drugs. The potential to protect any intellectual property from this project will be kept under review, with a view to future commercial exploitation. Results will also be shared with patient groups in St Paul's Eye Hospital, ensuring end-user engagement. Output from this project will stimulate research into novel routes of ocular drug delivery and further development of in vitro modelling of the eye. Both aspects of the research will be of great interest to academic and industrial researchers. This project will deliver a novel, drug-containing oil that can release drugs at therapeutic levels over several weeks and that will be ready to be tested in animals prior to human trials. This is designed to be an effective therapy for a sight-threatening condition that at the moment has no reliable treatment.

The IPS Fellow will coordinate the knowledge exchange strategy for Nuclear Physics, Particle Physics and Accelerator Science within the Department of Physics. Healthcare: The University of Liverpool, Department of Physics is one of only three national training providers for the new Modernising Scientific Careers (MSC) Medical Physics MSc, funded by the NHS. This was a highly successful bid, with Liverpool being ranked first against stiff competition. This MSc is delivered in collaboration with the Royal Liverpool University Hospital NHS Trust, the Clatterbridge Centre for Oncology (CCO) and Clinical Engineering with the University of Liverpool. The trainees come from throughout the UK. This provides a unique opportunity to build collaborative research and Continuing Professional Development (CPD) partnerships within the Healthcare sector. The fellow will coordinate these efforts and will help establish a new Medical Physics research institute within the University of Liverpool, which is a strategic goal of the University in its current planning. Security: The Fellow will help coordinate the exploitation of the sensor technology and associated instrumentation and techniques that exists within the research groups. The fellow will help consolidate existing relationships with partner organisations by showcasing the full breadth of STFC science activity. New opportunities for funding R+D will be identified together with establishing relationships with new companies. Energy: Liverpool scientists and engineers are working together as part of a new University Institute focused on research into energy. The Stephenson Institute is developing clean and sustainable energy technologies including hydrogen generation and storage, solar harvesting, wind and marine energy and fusion technology. The institute is in the process of developing expert networks, including policy-makers and management, to highlight global energy and sustainability issues. Making links with far eastern energy providers and attempting to attract a large investment from the University of Liverpool Energy campus we believe will be an important role of the fellow. The IPS Fellow will be fully engaged in this process, ensuring the opportunities for STFC science are fully exploited. The University of Liverpool Engineering, Electrical Engineering and Physics Departments are in the process of forming a Nuclear Engineering alliance which will maximise the exploitation of institutional expertise in autonomous systems, sensors and virtual engineering. The IPS Fellow will help coordinate the relationship between the alliance and external stakeholder organisations such as the National Nuclear Laboratory (NNL) and Sellafield Ltd. IT Developments: The Department was an early developer of large scale computing building the first large scale COTS cluster in n Europe in 2000 (MAP) and innovated specialized middleware . Subsequently the group invested in Grid computing and, at the same time founded the AiMeS Institute for commercial applications with NWDA and EW funding. This led to commercial spin-offs (AiMeS Grid Services) totally independent of the University currently delivering these Grid Services to the wider community. The Departments IT cluster activities, through also led to the introduction /choice of Force10 (now DELL) switches as the core switch technology at CERN; an example of beneficial relationship between industry and research. The group is now (separately from this request) bidding (with computer science partners) to develop a new generation of computers, based on a next generation of GPU chip and switch technology that aims to deliver a factor 1000:1 improvement in performance price of useable CPU cycles within the next decade. The IPS fellow will play a pivotal role in attracting commercial partners and carefully managing the IP issues that will arise.

Infection is the main cause of delayed healing in closed surgical wounds, traumatic and burn wounds, and chronic skin ulcers. Infection control for wounds is a contentious issue, particularly against a background of the antimicrobial resistance (AMR) epidemic. Furthermore, treatment of wound infections represents a significant economic burden on NHS resources and the quality of life of patients. Dressings and bandages have a major part to play in the modern management of wounds, with silver-containing dressings being the most commonly used for skin wounds. While these treatments have made great strides in reducing microbial bioburden, there may be potential cytotoxic issues regarding high concentrations of silver needed for reducing infection. Nitric oxide (NO) is a potent antimicrobial agent and has a proven role in wound repair which makes it an excellent candidate for the treatment of wound infections. The aim of this HIP is to improve upon the current silver technologies by embedding NO releasing silver nanoparticles (NP) into state of the art prototype bandages that will exploit NO's dual wound repair and antimicrobial function. These nanoparticles have been developed with previous EPSRC-funded funding (EP/M027325/1 Engineering Nitric Oxide Delivery Platforms for Wound Healing Applications) and we have shown the NO releasing nanoparticles to be extremely potent at killing bacteria present at very high concentrations. This proposal builds on this work by taking on a "personalised medicine" approach and tailoring release rates and concentrations of NO in different formulations for treating infections in the skin and eye. We have brought together clinical project partners with specific and complementary skills in skin wound infection and healing, and surface ocular wound infection and healing. Our commercial partners include a world leading US company that specialises in the fabrication, characterisation, and integration of nanomaterials into products and systems and a UK based SME that is at the forefront of reconstructed in vitro skin technologies that is innovating skincare research and development. Through this partnership, we will develop the clinical applicability, and the technical and commercial viability of antimicrobial NO releasing nanoparticles and their incorporation into bandages to accelerate the bench-to-clinic impact of the proposed research. NO-releasing nanoparticles will be fabricated and optimised to deliver a controlled and sustained release of the therapeutic. We have successfully tethered NO releasing functional groups to silver and gold nanoparticles with control over NO payload. These are first linked to a high molecular weight polymer coatings and then the polymer is conjugated to the particle to ensure high stability. We will optimise the rate of delivery and the amount of site-specific generated NO by controlling the size and shape of the NPs. All NP preparations will be evaluated for their antimicrobial activity against clinically relevant bacterial and fungal strains and their cytocompatibility. These nanoparticles will then be embedded into prototype bandages made from either electrospun polyurethane and alginate or peptide hydrogels depending on their potential application to skin or corneal wounds, respectively. The efficacy of the bandages containing the NO releasing NPs will be tested in in vitro assays and in ex vivo and in vitro 3D models. The development of this technology offers sustainable effective and economic solutions without contributing to the AMR epidemic while simultaneously participating in scientifically excellent, industrially relevant research.

This Healthcare Impact Partnership will use drug delivery technologies previously invented by us to develop novel, injectable devices to provide targeted, controlled and sustained drug delivery to the inside of the eye. These devices will address unmet clinical needs in two groups of patients. In addition, we will develop sophisticated benchtop and computer models of drug release in the eye, to allow us to speed up development and reduce the amount of animal testing required to use the devices in humans. Over 5.7 million people in the UK are living with sight-threatening eye conditions. These include conditions that can develop as a result of diabetes, macular degeneration and retinal detachment. The current best practice for treatment of the scarring that can follow retinal detachment is injection of silicone oil into the eye to replace the vitreous. It has been proposed that, in addition to the oil, sustained drug delivery could help reduce the development of scarring. We have previously developed technology to achieve controlled, extended release of drugs from silicone oils, and now wish to apply these technologies to silicone oils that are suitable for use in patients. Treatment for other sight-threatening conditions requires patients to have frequent injections of drugs directly into the eye over many years. This can be uncomfortable and inconvenient for patients, places a burden on the healthcare system and is not feasible in developing countries. A small number of drug delivery devices that reduce the number of injections needed are available, but these must either be removed once the drug release is complete, or, if the device is degradable, do not last much longer than standard injections. We have previously developed technology to make drugs into nanoparticles. We will develop a drug delivery system constructed of nanoparticles inside a material that forms a gel when it is injected into the eye. After the drug has been released, the gel would degrade into non-toxic components. The advantages of this over existing devices are that this technology could be tailored in terms of the drug and dosing, and that higher doses will be possible due to the use of nanoparticles. Both of our delivery devices are injectable, and will improve patient outcomes, particularly in developing countries and patients that present late. Our team is multidisciplinary, including academics specialising in ophthalmic biomaterials and drug delivery. A clinical ophthalmologist specialising in drug delivery will ensure that our technologies are suitable for clinical use. We will also engage with patients groups, who will help inform our development strategy. In order to accelerate the technologies towards the production of devices that are suitable for use in patients, we have partnered with a company who manufacture silicone oil products used to treat retinal detachment. With their expertise, we will be able to ensure that we include certain crucial aspects as we develop our technologies, such as how to scale up manufacture from the laboratory to that suitable for commercial use, and the generation of data that is required for the products to gain a licence for clinical use. Another commercial partner specialising in the production of models to replace animal testing will help us optimise our models, and promote their use to other organisations who are interested in reducing animal use. We will apply our silicone oil-based drug release technology to commercially-available oils, ensuring the resulting product has appropriate physical properties to remain functional in the eye, is not toxic, and has optimal drug release. We will also develop our nanoparticle system, optimising physical, drug-release and toxic properties. At the same time, we will develop existing benchtop and computer models so that they will be able to predict drug release from our devices.