The need to keep Britain's ageing population economically active has prompted government policies aimed at extending working lives. However, working beyond the traditional retirement age may not be feasible for those with major health problems of ageing and, depending on occupational and personal circumstances (e.g. savings, retirement intentions, domestic responsibilities, whether work is arduous, rewarding), might be either good or bad for health. Non-medical circumstances, including the design of work and workplace policies, may also hinder or harm prospects of job retention. Better information on these questions has many potential uses - e.g. to optimise government and employer policies; to identify interventions that may help older workers with health problems to remain in work; to alert doctors to medical problems associated with poor vocation outcomes; and to inform fitness for work decisions; to improve the design of work for older people; evidence on health, ageing, and risk of occupational injury can be used to ensure older workers are placed in safe work and that, where possible, their employment opportunities are not restricted without good justification. We are being funded by the charity Arthritis Research UK to recruit and follow 6,000 men and women aged 50-64 years from some 18 general practices in England. The practices contribute to the Clinical Practice Research Datalink (CPRD), a research database maintained by the government's Medicines and Healthcare Products Regulatory Agency (MHRA). The CPRD contains a log of every medical consultation episode associated with significant events, illnesses, or medical activity (diagnosis, referral, prescription, death etc) among the patients of participating general practices. These data are pseudo-anonymised (only identifiable by an ID code) and collected by MHRA from 250 practices in England and Wales, from which we will sample practices. CPRD linkage offers compelling scientific and logistic advantages. In particular, because we will access the entire GP medical records of participants in selected areas of inquiry, we can pursue our study questions using a hugely detailed database in which many health events and their timings are objectively corroborated. This will enable us to explore the effect of health on work, and vice versa, at a level of detail that is not feasible in periodic interviewer-administered or postal surveys. Moreover, the data will be captured at very low cost relative to alternative means of acquiring the same information. ARUK has provided funding only to investigate the impact of common musculoskeletal disorders (MSDs) of ageing on work retention and the effect of deferring retirement on musculoskeletal health. This leaves us short, particularly in respect of research assistant time to develop the cohort and computing and statistical time to analyse the many non-MSD problems that the dataset offers. We hope through this bid to maximise the value of the cohort, and the efforts of participants, by extending our analysis to a much broader range of health conditions and their impact on work participation. Funding will be used to purchase more research assistant, data programmer and statistical time, but many of the other costs (eg mailing, clerical, payment to practices) are already met and many of the practical hurdles (eg ethics and governance permissions, access rights to CPRD data) have already been resolved. The MHRA's research director is a collaborator in this application. Patients from participating general practices who agree to be studied will complete questionnaires about their work and home circumstances, initially over a 3-year follow-up. With their written permission, we will access their health data via the CPRD and link this to their questionnaire data. The inter-relation of changes in employment (with reasons) and changes in health (eg major new illnesses, new treatments, mortality) will be examined statistically.

While it has been recognised for some time that small particles from vehicle exhausts and other traffic related pollutants cause a range of health effects, policy within the UK and Europe has not directly targeted these. Emissions from vehicles and ambient air itself are regulated in terms of total particles, with no specific targeting of one component or another. While this is clearly prudent in that it potentially drives reductions in all types of particles, it is also inefficient as it is likely that some particles (or particle components) are more toxic than others. This project seeks to elucidate the more toxic components of the pollution mix in London, with particular emphasis on traffic generated particles. If successful this will inform a more focussed and more efficient policy process for regulating vehicle emissions and ambient air quality. As well as regulating vehicle emissions and ambient air, policy makers - particularly at local and regional government level-can influence air pollution impacts through traffic management and wider planning decisions. Here the project will provide better information on spatial and temporal exposures and their relation to adverse impacts of air quality. This dynamic exposure information will be a major step forward in assessing the scope for more focussed traffic and infrastructure planning and management in London, with possible applications elsewhere in the UK. Even though there is a substantial literature confirming the impact of traffic pollution on health there are still substantial gaps. There is very strong evidence that exposure to traffic pollution causes asthma exacerbations in children and reasonably strong evidence that it may cause other health effects including the onset of childhood asthma, non asthma respiratory symptoms, impaired lung function, total and cardiovascular mortality and cardiovascular morbidity. In this project we will undertake a number of new investigations to examine the relationship between chronic exposure to traffic pollution and health. These will include studies of mothers in pregnancy right through to senior citizens. These innovative studies will include health outcomes rarely if ever available for investigation of air pollution effects (e.g. primary care data, child cardiovascular risk factors). The use of exposure metrics on a fine spatial scale that are in routine use for policy in London will enable exposure response relationships to be used for quantifying policy options in terms of health impact. Further this will enable us to evaluate the health impact of trends in exposure to traffic related air pollution, most specifically the Low Emission Zone for London (LEZ).

Regenerative devices (scaffolds, biomaterials and interventions) which can repair and regenerate tissues using the patients` own cells, can be translated into successful clinical products and deliver patient benefit at much lower cost and risk and in shorter timescales then other regenerative therapies such as culture expanded cell therapies or molecular (drug) therapies. It is estimated that the global market for regenerative devices will grow to £50bn by 2020 and this offers a real opportunity to grow a £1bn per year industry in the UK in this field. The UK has genuine research strengths in the areas of biomaterials and tissue engineering, musculoskeletal mechanics (prioritised by EPSRC) and regenerative medicine. Regenerative medicine is one of the eight great technologies prioritised across the Research Councils. Research discoveries, new knowledge, outputs and outcomes are often not ready for uptake by industry to take forward through product development to the market and patient benefit. New technologies need to be advanced and de-risked. The clinical needs, potential products and markets need to be defined in order to make them attractive for investment, product development and clinical trials by industry. In the Medical Technologies Innovation and Knowledge Centre (MTIKC) Phase 1, working with industry and clinical partners, we have developed a professional innovation team and a unique innovation and translation process, creating a multidisciplinary research and innovation ecosystem. We have successfully identified research outcomes and new knowledge and created, advanced and translated technology across the innovation valley of death, enabling successful investment (over £100m) by industry and the private sector in new product development. Some products have already progressed to clinical trials and commercialisation and are realising patient benefits. We have established a continuous innovation pipeline of over fifty proofs of concept technology projects. Over the next five years in MTIKC Phase 2, we will address unmet clinical needs and market opportunities in wound repair, cardiovascular repair, musculoskeletal tissue repair, maxillofacial reconstruction, dental reconstruction and general surgery and diversify our research supply chain to over ten other Universities. We will support 150 collaborative projects with industry and initiate forty new industry inspired and academically led proof of concept projects, which are predicted to lead to a further £100m investment by the private sector in subsequent product development. This will enable a sustainable research and product development pipeline to be established in the UK which will support a £1bn / year industry in regenerative devices beyond 2020.

Regenerative medicine (RM) is a convergence of conventional pharmaceutical sciences, medical devices and surgical intervention employing novel cell and biomaterial based therapies. RM products replace or regenerate damaged or defective tissues such as skin, bone, and even more complex organs, to restore or establish normal function. They can also be used to improve drug testing and disease modelling. RM is an emerging industry with a unique opportunity to contribute to the health and wealth of the UK. It is a high value science-based manufacturing industry whose products will reduce the economic and social impact of an aging population and increasing chronic disease.The clinical and product opportunities for RM have become clear and a broad portfolio of products have now entered the translational pipeline from the science bench to commercialisation and clinical application. The primary current focus for firms introducing these products is first in man studies; however, success at this stage is followed by a requirement for a rapid expansion of delivery capability - the 'one-to-many' translation process. This demands increasing attention to regulatory pathways, product reimbursement and refinement of the business model, a point emphasised by recent regulatory decisions demanding more clarity in the criteria that define product performance, and regulator initiatives to improve control of manufacturing quality. The IMRC will reduce the attrition of businesses at this critical point in product development through an industry facing portfolio of business driven research activities focussed on these translational challenges. The IMRC will consist of a platform activity and two related research themes. The platform activity will incorporate studies designed to influence public policy, regulation and the value system; to explore highly speculative and high value ideas (particularly clinically driven studies); and manufacturing-led feasibility and pilot studies using state of the art production platforms and control. The research themes will focus on areas identified as particular bottlenecks in RM product translation. The first theme will explore the delivery, manufacturing and supply processes i.e. the end to end production of an RM product. Specifically this theme will explore using novel pharmaceutical technology to control the packaged environment of a living RM product during shipping, and the design of a modular solution for manufacturing different cell based therapies to the required quality in a clinical setting. The second research theme will apply quality by design methods to characterise the quality of highly complex RM products incorporating cells and carrier materials. In particular it will consider optical methods for non-invasive process and product quality control and physicochemical methods for process monitoring.The IMRC will be proactively managed under the direction of a Board and Liaison Group consisting of leading industrialists to ensure that the Centre delivers maximum value to the requirements of the business model and assisting the growth of this emerging industry.

The lifETIME CDT will focus on the development of non-animal technologies (NATs) for use in drug development, toxicology and regenerative medicine. The industrial life sciences sector accounts for 22% of all business R&D spend and generates £64B turnover within the UK with growth expected at 10% pa over the next decade. Analysis from multiple sources [1,2] have highlighted the limitations imposed on the sector by skills shortages, particularly in the engineering and physical sciences area. Our success in attracting pay-in partners to invest in training of the skills to deliver next-generation drug development, toxicology and regenerative medicine (advanced therapeutic medicine product, ATMP) solutions in the form of NATs demonstrates UK need in this growth area. The CDT is timely as it is not just the science that needs to be developed, but the whole NAT ecosystem - science, manufacture, regulation, policy and communication. Thus, the CDT model of producing a connected community of skilled field leaders is required to facilitate UK economic growth in the sector. Our stakeholder partners and industry club have agreed to help us deliver the training needed to achieve our goals. Their willingness, again, demonstrates the need for our graduates in the sector. This CDT's training will address all aspects of priority area 7 - 'Engineering for the Bioeconomy'. Specifically, we will: (1) Deliver training that is developed in collaboration with and is relevant to industry. - We align to the needs of the sector by working with our industrial partners from the biomaterials, cell manufacture, contract research organisation and Pharma sectors. (2) Facilitate multidisciplinary engineering and physical sciences training to enable students to exploit the emerging opportunities. - We build in multidisciplinarity through our supervisor pool who have backgrounds ranging from bioengineering, cell engineering, on-chip technology, physics, electronic engineering, -omic technologies, life sciences, clinical sciences, regenerative medicine and manufacturing; the cohort community will share this multidisciplinarity. Each student will have a physical science, a biomedical science and a stakeholder supervisor, again reinforcing multidisciplinarity. (3) Address key challenges associated with medicines manufacturing. - We will address medicines manufacturing challenges through stakeholder involvement from Pharma and CROs active in drug screening including Astra Zeneca, Charles River Laboratories, Cyprotex, LGC, Nissan Chemical, Reprocell, Sygnature Discovery and Tianjin. (4) Embed creative approaches to product scale-up and process development. - We will embed these approaches through close working with partners including the Centre for Process Innovation, the Cell and Gene Therapy Catapult and industrial partners delivering NATs to the marketplace e.g. Cytochroma, InSphero and OxSyBio. (5) Ensure students develop an understanding of responsible research and innovation (RRI), data issues, health economics, regulatory issues, and user-engagement strategies. - To ensure students develop an understanding of RRI, data issues, economics, regulatory issues and user-engagement strategies we have developed our professional skills training with the Entrepreneur Business School to deliver economics and entrepreneurship, use of TERRAIN for RRI, links to NC3Rs, SNBTS and MHRA to help with regulation training and involvement of the stakeholder partners as a whole to help with user-engagement. The statistics produced by Pharma, UKRI and industry, along with our stakeholder willingness to engage with the CDT provides ample proof of need in the sector for highly skilled graduates. Our training has been tailored to deliver these graduates and build an inclusive, cohesive community with well-developed science, professional and RRI skills. [1] https://goo.gl/qNMTTD [2] https://goo.gl/J9u9eQ