In the diagnosis and treatment of disease, clinicians base their decisions on understanding of the many factors that contribute to medical conditions, together with the particular circumstances of each patient. This is a "modelling" process, in which the patient's data are matched with an existing conceptual framework to guide selection of a treatment strategy based on experience. Now, after a long gestation, the world of in silico medicine is bringing sophisticated mathematics and computer simulation to this fundamental aspect of healthcare, adding to - and perhaps ultimately replacing - less structured approaches to disease representation. The in silico specialisation is now maturing into a separate engineering discipline, and is establishing sophisticated mathematical frameworks, both to describe the structures and interactions of the human body itself, and to solve the complex equations that represent the evolution of any particular biological process. So far the discipline has established excellent applications, but it has been slower to succeed in the more complex area of soft tissue behaviour, particularly across wide ranges of length scales (subcellular to organ). This EPSRC SoftMech initiative proposes to accelerate the development of multiscale soft-tissue modelling by constructing a generic mathematical multiscale framework. This will be a truly innovative step, as it will provide a common language with which all relevant materials, interactions and evolutions can be portrayed, and it will be designed from a standardised viewpoint to integrate with the totality of the work of the in silico community as a whole. In particular, it will integrate with the EPSRC MultiSim multiscale musculoskeletal simulation framework being developed by SoftMech partner Insigneo, and it will be validated in the two highest-mortality clinical areas of cardiac disease and cancer. The mathematics we will develop will have a vocabulary that is both rich and extensible, meaning that we will equip it for the majority of the known representations required but design it with an open architecture allowing others to contribute additional formulations as the need arises. It will already include novel constructions developed during the SoftMech project itself, and we will provide many detailed examples of usage drawn from our twin validation domains. The project will be seriously collaborative as we establish a strong network of interested parties across the UK. The key elements of the planned scientific advances relate to the feedback loop of the structural adaptations that cells make in response to mechanical and chemical stimuli. A major challenge is the current lack of models that operate across multiple length scales, and it is here that we will focus our developmental activities. Over recent years we have developed mathematical descriptions of the relevant mechanical properties of soft tissues (arteries, myocardium, cancer cells), and we have access to new experimental and statistical techniques (such as atomic force microscopy, MRI, DT-MRI and model selection), meaning that the resulting tools will bring much-need facilities and will be applicable across problems, including wound healing and cancer cell proliferation. The many detailed outputs of the work include, most importantly, the new mathematical framework, which will immediately enable all researchers to participate in fresh modelling activities. Beyond this our new methods of representation will simplify and extend the range of targets that can be modelled and, significantly, we will be devoting major effort to developing complex usage examples across cancer and cardiac domains. The tools will be ready for incorporation in commercial products, and our industrial partners plan extensions to their current systems. The practical results of improved modelling will be a better understanding of how our bodies work, leading to new therapies for cancer and cardiac disease.

Digital twins are a fusion of digital technologies considered by many leading advocates to be revolutionary in nature. Digital twins offer exciting new possibilities across a wide range of sectors from health, environment, transport, manufacturing, defence, and infrastructure. By connecting the virtual and physical worlds (e.g. cyber-physcial), digital twins are able to better support decisions, extend operational lives, and introduce multiple other efficiencies and benefits. As a result, digital twins have been identified by government, professional bodies and industry, as a key technology to help address many of the societal challenges we face. To date, digital twin (DT) innovation has been strongly driven by industry practitioners and commercial innovators. As would be expected with any early-adoption approach, projects have been bespoke & often isolated, and so there is a need for research to increase access, lower entry costs and develop interconnectivity. Furthermore, there are several major gaps in underpinning academic research relating to DT. The academic push has been significantly lagging behind the industry pull. As a result, there is an urgent need for a network that will fill gaps in the underpinning research for topics such as; uncertainty, interoperability, scaling, governance & societal effects. In terms of existing networking activities, there are several industry-led user groups and domain-specific consortia. However, there has never been a dedicated academic-led DT network that brings together academic research teams across the entire remit of UKRI with user-led groups. DTNet+ will address this gap with a consortium which has both sufficient breadth and depth to deliver transformative change.

Our vision is to use continuous photochemistry and electrochemistry to transform how fine chemicals, agrochemicals and pharmaceuticals are manufactured in the UK. We aim to minimize the amount of chemicals, solvents and processing steps needed to construct complex molecules. We will achieve this by exploiting light and/or electricity to promote more specific chemical transformations and cleaner processes. By linking continuous photochemistry and electro-chemistry with thermal flow chemistry and environmentally acceptable solvents, we will create a toolkit with the power to transform all aspects of chemical synthesis from initial discovery through to chemical manufacturing of high-value molecules. The objective is to increase efficiency in terms of both atoms and energy, resulting in lower cost, low waste, low solvent footprints and shorter manufacturing routes. Historically photo- and electro-chemistry have been under-utilised in academia and industry because they are perceived to be complicated to use, difficult to scale up and engineer into viable processes despite their obvious environmental, energy and cost benefits. We will combine the strategies and the skills needed to overcome these barriers and will open up new areas of science, and deliver a step-change (i) providing routes to novel molecular architectures, hard to reach or even inaccessible by conventional methodologies, (ii) eliminating many toxic reagents by rendering them unnecessary, (iii) minimizing solvent usage, (iv) promoting new methodologies for synthetic route planning. Our proposal is supported by 21 industrial partners covering a broad range of sectors of the chemistry-using industries who are offering £1.23M in-kind support. Therefore, we will study a broad range of reactions to provide a clear understanding of the most effective areas for applying our techniques; we will evaluate strategies for altering the underlying photophysics and kinetics so as to accelerate the efficiency of promising reactions; we will transform our current designs of photochemical and electrochemical reactors, with a combination of engineering, modelling and new fabrication techniques to maximize their efficiency and to provide clear opportunities for scale-up; we will exploit on-line analytics to accelerate the optimisation of continuous photochemical and electrochemical reactions; we will design and build a new generation of reactors for new applications; we will identify the most effective strategies for linking our reactors into integrated multi-step continuous processes with minimized waste; we will demonstrate this integration on at least one synthesis of a representative pharmaceutical target molecule on a larger scale; we will apply a robust series of sustainability metrics to benchmark our approaches against current manufacturing.