SummaryContinued improvement in the nation's health depends upon the efficient development of affordable replacement human tissue and related therapies; an acute shortage of willing organ donors and the shortcomings of conventional therapies leads to the preventable death of many patients each year. The next healthcare revolution will apply regenerative medicines, creating biological therapies or substitutes for the replacement or restoration of tissue function lost through failure or disease. However, whilst science has revealed the potential, and early products have shown the power of such therapies, there is now a need for the long term supply of people properly trained with the necessary skills to face the engineering and life science challenges before the predicted benefits in human healthcare can be realised. Because the products arising from this technology differ significantly from those made by mainstream pharmaceutical companies, training programmes currently available are poorly equipped to meet the demand for increasing numbers of appropriately trained personnel. We estimate that the number of engineers with the necessary skills to interact `on the same level' with cutting edge bioscientists and clinicians is very small, perhaps no more than 100 nationally; in such a small community 50 newly trained PhD's will have a very large impact. Here we propose a new UK based DTC in Regenerative Medicine integrated across three Universities with highly complementary expertise where students will be trained in the core skills needed to work at the life science/engineering interface and then engaged in strategic research programmes designed to address the major challenges in the field. This will ensure that the necessary people and enabling technologies are developed for the UK to lead in this rapidly growing worldwide marketplace.

Chronic diseases are a major challenge for human health in the 21st century. The UK and worldwide burden of chronic disease is expected to increase in future years. Chronic Obstructive Pulmonary Disease (COPD) is an important chronic disease of the chest and is a leading cause of disability among older people. Muscle wasting and weakness is an important feature of COPD. Patients with muscle wasting are more disabled, have a poorer prognosis and require more healthcare resources. Loss of muscle bulk and function is important because it may be a treatable consequence of a condition in which the underlying lung disease is usually irreversible. The value of this approach is illustrated by the benefits of physical training, which have been clearly demonstrated in COPD. However, little is known about the causes of muscle wasting and weakness or the mechanisms by which physical training improves muscle function in COPD. We have recently identified genes involved in the regulation of muscle wasting and growth in healthy young and elderly humans and demonstrated that the functioning of these genes is profoundly affected by periods of immobility and exercise. Recent work has also demonstrated that dietary supplementation of protein enhances muscle growth during exercise training in healthy humans. We will extend these observations to study muscle wasting and growth in the clinical setting of COPD. We will study the functioning of genes recently identified as important in the regulation of muscle growth and wasting in patients with COPD compared with healthy volunteers of the same age. We will also study the effects of an eight-week lower limb strength-training programme on the functioning of these genes. This will help us understand how training works and how training affects the genes that regulate muscle growth. It may be beneficial to supplement individuals with additional dietary protein at the time of training. We will test this theory by randomly allocating patients in the study to receive a protein rich drink or a non-nutritive placebo after each bout of training. We will also measure muscle bulk and muscle function during the study. This research will provide new insights into the genetic mechanisms of muscle wasting and weakness and how the functioning of these genes can be influenced by interventions such as training and nutrition. This information will be a significant advance in the development of new treatments aimed at improving muscle function in chronic diseases such as COPD.

The Office for Artificial Intelligence (AI) estimates that AI could add £232 billion to the UK economy by 2030, increasing productivity in some industries by 30%. However, to be truly transformational, the integration of AI throughout the global economy requires understanding and trust in the AI systems deployed. The super-human ability for decision-making in new AI systems requires huge volumes of data with thousands of variables, dependencies and uncertainties. Unregulated application of uncertified data-driven AI, limited by data bias and a lack of transparency, brings huge risks and necessitates a community-wide change. AI systems of the future must also be able to learn on-the-job to avoid becoming a high-interest credit card of huge technical debt. There is thus a timely and unmet need for a new theory and framework to enable the creation and analysis of data-driven AI systems that are adaptive, resilient, robust, explainable, and certifiable, with provable and practically relevant performance guarantees. This ambitious fellowship, ARaISE, will deliver a radically new framework for the creation of beneficial data-driven AI systems advancing far beyond classical theories by including certifiable robustness and learning in the problem setting. These new theories will enable a formal understanding of the fundamental limits of large-scale data-driven AI, independent of the application area and learning algorithms. This will enable AI practitioners, through understanding such limitations, to influence policy and prevent incidents before they occur. By connecting different and disparate areas of AI and Machine Learning, working with a world-class team of experts, and by engaging with stakeholders across strategic UK industries and sectors (Healthcare, Manufacturing, Space and Earth Observation, Smart Materials, and Security), ARaISE will create high-value, trustworthy, transformative and responsible AI, capable of reliably 'learning on-the-job' from humans to guarantee capability and trust. Novel human-centric AI, designed to function for the benefit of society, will complement and connect to existing work in the AI research arena, enabling co-development with project partners and focus on strategic industry challenges to ensure real-world relevance is built into research programme and its outputs, facilitating capacity and capability growth. ARaISE will generate gold standard tools for tasks that are currently heavily reliant upon human input and will support long-term global transformation. Impact and knowledge exchange activities, embedded throughout this programme of work, will support uptake of developed novel AI systems and, through leadership and ambassadorial activities, will support a step-change in how AI systems are built and maintained to ensure resilient, robust, adaptive and trustworthy operation. The inclusive research programme has been designed to support the career development of the project team and wider stakeholder group maximising the potential for flexible career paths whilst maintaining flexibility to creatively support the team to develop exciting new technology with real world relevance and guide future AI research. The issues of AI and ethics underpin the programme with responsible research and innovation embedded throughout its activities. Raising public and AI practitioners' awareness, and ultimately influencing policy by active engagement with the UK and AI ethics expertise and policymakers, will ensure that the outcomes are socially beneficial, ethical, trusted and deployable in real world situations. Planned engagement with the ATI, CDTs, partners, and their networks, the development of new partnerships, methodologies and applications, will encourage links between these organisations, build UK expertise, skills and capacity in AI and contribute to realising government investment in UK Societal Challenges and ensure that the UK remains at the forefront of the AI revolution.

NIMRC's research portfolio is at the heart of the national manufacturing agenda and is active in the generation of patents and the construction of full scale demonstrators to enhance technology transfer. The Centre has strong links with industry in a range of sectors including aerospace, automotive, instrumentation, power engineering, steel, textiles and clothing, and consumer product sectors. With the exception of a small number of blue-skies projects, all projects are driven by industrial need. During the past 3 years, the Nottingham Innovative Manufacturing Research Centre (NIMRC) has continued to succeed in its stated objectives. By exploiting synergies between themes and research strands within the Centre and with other academic groups and industry outside the Centre, NIMRC has continued to expand its world-leading research portfolio and develop new directions. From a start of 8 principal investigators in the IMRC, this year we have an additional 15 investigators participating in current projects within the portfolio, complemented by 22 researchers and 29 research students. In the past 3 years, 9 students have been been awarded a PhD and another 7 are currently submitting their dissertations.The quality, timeliness and novelty of NIMRC's research is highlighted by its publication record. Since the Centre began, staff have published widely in peer review journals and presented at prestigious international conferences.The IMRC status has attracted a wider research community both in the University and without. The NIMRC continues to develop strategic partnerships with research groups outside the University and include many internationally recognised centre's of manufacturing excellence. The Centre also has strong links with other IMRCs. Already, NIMRC has collaborative research projects with Warwick, Bath, Cranfield and Loughborough IMRCs. NIMRC is also participating in the Grand Challenge 3D Mintigration related to the economic Manufacture of 3D Miniaturised Devices . NIMRC has made excellent progress during the last 3 years towards its stated objectives. It believes that the future research strategy it has developed will continue to address both the immediate and longer term needs of the manufacturing industry and it looks forward to providing the enabling research needed to improve the competitiveness of UK plc. The importance of NIMRC's world-class research is demonstrated in the composition of the Industrial Advisory Board which includes 20 senior industrialists from well established UK manufacturing sectors. The Board is impressed with the work of the Centre and the rapport with the Board of PIs. Board members have their own examples of how their company has benefited from the work of the NIMRC. In summary, Rolls-Royce and the Industrial Advisory Board fully support the activities of the NIMRC and will continue to do so. Chair of NIMRC Industrial Advisory Board, Mr Stephen Burgess, Manufacturing Process and Technology Director, Rolls-Royce Plc.

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