Thromboembolic disease and associated blood coagulation abnormalities cause significant morbidity and mortality in Western society, with stroke being the third leading cause of death in the UK. The incidence of stroke increases markedly with age and is often higher in socially deprived areas. In stroke, the processes of endothelial and vascular damage, activation of the coagulation cascade and decreased fibrinolysis result in abnormal clots, often with excessively cross-linked fibrin networks. An unsatisfactory aspect of work in this area is that the microstructures of such clots are usually reported in only adjectival terms (e.g., dense or tight ) - usually on the basis of a visual inspection of fragments of dessicated clots in SEM micrographs. Early detection of clots is vital. Early clotting events may contribute to a pro-thrombotic state which exacerbates the disease state and thrombotic states can be followed rapidly by haemorrhagic states due to adverse changes in clot structure. The available therapeutic options informed by early detection and characterisation are greatly enhanced.New technology is essential to address shortcomings in this area. This project will exploit our recent advances in blood clot detection and ultra-sensitive nanomaterials development for device applications to overcome these shortcomings. Under a Royal Society Brian Mercer Award and an EPSRC Portfolio Partnership Award, in collaboration with the NHS, we have developed a new haemorheological technique for the early detection and characterisation of blood clots. This has led to the discovery that the incipient clot's fractal microstructure is a biomarker for the conditions of clot formation, including therapeutic intervention. The significance of this discovery stems from the incipient clot's role as the microstructural template for ensuing clot development. In parallel work we have demonstrated the controlled reproducible growth of vertical arrays of ZnO nanowires and have confirmed their electrical current generation capabilities. Our Grand Challenge proposal involves combining this nanotechnology with our haemorheological work to develop the first point of care (POC) device capable of the early detection and characterisation of abnormal clots. By a point of care device we refer to technology suitable for widespread use outside hospitals (i.e., within pharmacies and surgeries) and which will ultimately be developed for use by patients at home. This will exploit the piezoelectric properties of ZnO nanowire arrays as a transducer to detect shear wave propagation within coagulating blood. Our aim is to drastically improve the sensitivity of early clot detection for more accurate assessments of (i) coagulation abnormalities and (ii) therapeutic targeting of abnormal clots at the earliest stage of development. The project involves in vivo and in vitro disease model (Stroke) work at University of London, and work intended to enable our device to perform a therapeutic function. In this way we propose to lay the foundations for a POC system for Patient Self Assessment and Patient Self Management in anticoagulant applications, in addition to a new technological basis for thromboembolic disease screening. The project also includes anticoagulated Stroke patient volunteers at Morriston NHS Hospital.We have a highly multidisciplinary Team with internationally leading expertise in rheometry and haemorheology; nanotechnology, nanomaterials and nanofabrication; nanomedicine and drug delivery; and human-device interaction aspects of medical instrument design. We have two partners. The first is the NHS who will provide clinical facilities and governance of clinical research. Our second partner is Boots Centre for Innovation (BCI) whose involvement anticipates healthcare provision involving POC applications in next-generation pharmacies. BCI's role is to inform design relating to customer needs/experience, the POC market and environment.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

This project will explore the largely unknown international history of British healthcare and beauty, using Boots the Chemists, Britain's most recognised chain pharmacist, as the central case study. The project spans the period from 1919, when the company posted its first sales agent overseas, to the streamlining of its divisions in 1980. It examines how Boots established itself as a prospector, retailer and manufacturer overseas, but also how it continually absorbed international influences as part of its home marketing strategies. Drawing on Boots' vast, underexplored archive (c.5,000 boxes of approximately 500,000 items), this project bridges medical, social, cultural, business, colonial and transnational history. The project team are not interested in writing a classic business biography of Boots' success and growth, rather they are interested in exploring what the Boots story reveals about the international dynamics of the British health and beauty industries. The central research question asks: How does Boots' international archive allow us to map the global networks that moulded and sustained British experiences of healthcare and beauty both at home and abroad? To answer this, thematically focused work packages will recreate the life-cycles of key products within six product domains (pain management, personal hygiene, surgical supplies, vitamins, perfumes, and skincare) across local, national and international spaces. These six focal areas have been selected because of their ample archival resources and their potential to illustrate how complex imperial and other global networks of materials, knowledge and people underpinned the development of British healthcare and beauty, both at home and overseas. This pioneering research will appear in leading academic journals across the historical humanities and in a co-authored book. It will advance early career capacity by employing a full-time postdoctoral researcher, and provide additional opportunities for an already funded M4C doctoral student. Three interdisciplinary academic workshops will explore new perspectives on the internationalisation of the UK beauty and healthcare industries and will open the project to colleagues in geography, pharmacy, medicine, literature and linguistics. The project team will showcase findings via an easily navigable website featuring information about the project, links to relevant resources and quarterly updated project stories, attractively illustrated with archival images. Some of these stories will be authored by the project team and some by 'citizen researchers'. These contributors will be identified through call outs via social media, Boots newsletters, and the local press, and might be local history enthusiasts, former Boots employees or business people reflecting on historical context. Additional outreach will include two pieces of popular history, a high-profile public exhibition, with a touring component and accompanying public talks, timed to coincide with Boots' 175th anniversary in 2024. A further outreach strategy targets professional archivists via three initiatives i) working with Boots Archive staff to help inform their cataloguing and digitisation strategies; ii) holding three innovative 'Archive Roadshows' where team members visit other significant business archives (Unilever, Marks and Spencer, John Lewis) to reflect on the usefulness and accessibility of their resources; iii) hosting an Archive Study Day to bring together company archivists throughout the UK. Finally, team members will work with Nottinghamshire County Council to run two 'Knowledge Labs' to consider how this research might stimulate creative thinking about current issues facing the UK high street. Sessions will discuss not only how local growth is internationally informed, but also how international markets are heavily influenced by smaller local developments.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

At the forefront of global pharmaceutical research is the development of "intelligent" medicines which are effective, affordable and safe, for diseases that are poorly treated (for example, cancer, infections, cardiovascular disease and neurodegeneration). The ideal medicine could be taken by a variety of means (pill, injection or inhaler), but should only act on diseased tissue at a 'specific' site in the body. However, the ability to direct a drug to particular desired locations in the body is still a major scientific challenge. Drugs can easily be degraded en route to their target leading to quickly decreasing drug levels. Higher levels of medication do not circumvent this problem due to potentially increased side effects or toxicity. Some drugs can simply not be delivered to their target due to barriers within the body: the ability to reach specific disease sites while leaving healthy cells intact would mean not only better therapeutic outcomes, but better qualities of life for patients and carers. Benefits through better formulation and targeting will be very apparent for those diseases that are increasing in ageing populations, such as cancer, which is predicted to affect (directly or indirectly) 1 in 3 in the European population by 2020. For these and other devastating diseases new therapeutic regimens are urgently needed. Research into Advanced Therapeutics requires not just scientific innovation but also a changed training paradigm for the scientists involved. Many advanced therapeutic formulations are inherently in the 'nano' size range i.e. larger than conventional drugs such as ibuprofen and paracetamol, but smaller than human cells, and thus spanning the traditional domains of chemistry, biology and medicine. Developing the science of these emergent nanomedicines towards clinical products requires a new generation of researchers trained across multiple scientific disciplines. The Centre for Doctoral Training we propose builds on our existing close partnerships with leading industry and academic institutions world-wide to offer training in the diverse and challenging disciplines underlying pharmaceutical science. The proposed Centre will combine expertise in analytical and medicinal chemistry, with materials science, engineering, biology and industrial pharmaceutics, to equip researchers with the skills they need to develop the next generation of pharmaceutical products. Accordingly, the CDT offers wider benefits to society as researchers trained in the Centre will be attractive to the chemicals, engineering and materials sectors as well as healthcare and medicine. Within the proposed CDT we aim to continue our broad-based training approach, such that researchers will have innovation and entrepreneurial skills, so vital for the developing industry sector. This focus on translational and business skills helped a team from Nottingham in the existing CDT to be winners of the NanoCom business competition in 2012. Ultimately, improvements in the industry and practice of therapeutics combined with enhanced academy / industry pathways to translation offer many future advantages, not just to the science, industry and medical base, but to patients, carers and society as a whole.