Over the last decade excellent non-invasive sensing platforms have become available for capturing real-time health and lifestyle data, with the fitbit and Apple Watch being well known examples. However, current 'wearable' sensors all have major limitations: they connect to the body using straps and similar which do not maintain a good connection over long time periods; they have high power consumptions meaning the device must be taken off and recharged, at best, every couple of days; they contribute a significant amount to electronic waste. They are thus far from realising their true potential. This challenge is recognised by the EPSRC, with 'Disruptive technologies for sensing & analysis' being a core part of the 2015 Healthcare Technologies strategy. We propose to tackle this challenge by advancing novel material manufacturing approaches to realise next generation 'conformal' sensor nodes. This will make a disruptive next generation sensor platform for the very long term monitoring of a number of body parameters (motion, electrophysiological and temperature data) which is very different to current bio-sensing approaches. Our novel manufacturing will enable sensors which are: - Mounted on a conformal substrate, attaching directly to the skin without a strap, and maintaining contact for several days at a time. - Manufactured using inkjet printing to allow minimal waste and responsive manufacturing, potentially tailoring each sensor to each person. Graphene nanoparticle based inks will replace current silver nanoparticle inks which, due to the inert nature of graphene, avoids the electronic waste issues associated with silver inks. - Tailored with new ink and substrate formulations so that both the graphene ink and conformal substrate are 'transient'. That is, they work for a period of time and then naturally decompose into safe, inert and easily removed components, enabling easy use and disposal. - 3D in nature by using 'popup' structures manufactured on pre-stressed substrates. This will allow 'actuated antennas', coupling the mechanical and electromagnetic properties of a 3D antenna in order to allow simultaneous sensing and transmission using the antenna component, significantly reducing the device size as conventional instrumentation can be removed. - Ultra low power using a novel switching strategy to allow secure digital transmission over an RFID wireless link without the need for a dedicated, high power, analogue-to-digital converter microchip. - Increased in wireless powering range, by devising reduced size epidermal antennas that exploit magnetically coupled loops in tattoo antennas with under 3 times the surface area of current approaches, reducing ink use for digital fabrication. - Optimized for robustness to motion interference, allowing the collection of high quality signals in real-world, out-of-the-lab situations. - Suitable for scale-up manufacturing with roll-to-roll and/or sheet fed printing of key elements, integrating with pick and place capabilities. - Integrated into initial complete system demonstrators which will be showcased to our partners, covering the use of long term sensor nodes with people who are elderly and with children. Collectively these represent a step change beyond 'wearable' devices available today. Our new sensors will be customisable battery-less RFID tags that can operate more than a metre from a powered reader, stay attached for many days at a time, and with a controlled lifetime set by the transient nature of the manufacturing. At this early stage we do not propose to target any one clinical application area, but rather to make the next generation of technologies for conformal on-body sensor nodes that collect longitudinal information relevant to a number of disease areas. We will work with our partners through pathways to impact activities to maximise the possibility of exposure to relevant end users in healthcare scenarios.

Neuromuscular diseases (NMD) are an important group of disabling conditions affecting about 150,000 children and adults in the UK. They are caused by impairment of peripheral nerve and/or skeletal muscle function. Patients with these diseases develop muscle weakness and the severity can range from death in childhood or early adult life through to life long disability & dependence. Many patients also have heart and breathing muscle weakness which can add to disability and sometimes be fatal. These NMD conditions are commonly genetic and may run in families. They can also be acquired-for example through antibody attack as in "autoimmune" NMD or due to premature degeneration of muscle. Genetic examples include muscular dystrophy (~1 in 3500), Charcot Marie Tooth (CMT) neuropathy (~1 in 2500) and mitochondrial diseases (~1 in 5000). Acquired examples include chronic nerve inflammation (~1 in 1500) and a muscle degeneration/inflammation condition called inclusion body myositis (~1 in 10,000). It is clear that NMD represent an important unmet health burden for the nation. However, relative to other neurological diseases such as epilepsy and multiple sclerosis, NMD have received less attention by government and other UK funding bodies. This is despite the excellent clinical infrastructure provided by several large clinical neuromuscular centres and the nationally commissioned NHS funding for care and diagnosis of some NMD lead by MRC Centre PI's (eg congenital muscular dystrophy, channelopathies and mitochondrial diseases). Furthermore, there has been significant progress in NMD discovery science, frequently lead by internationally high profile UK clinicians and scientists, but translation of this scientific discovery into clear benefit for UK patients has been disappointing so far. We set up this MRC Centre to develop ways to bridge this "translational gap" between scientific discovery and patient benefit. We identified six main reasons (obstacles) why scientific discoveries were not clearly benefiting patients. We developed specific core activities to overcome each obstacle. Most notably we found there was a lack of UK trials culture for these conditions. That means that there were not many trials happening, doctors treating patients did not think there was much that could be done, and patients were not being given the opportunity to get involved in the research & trials that were happening. By setting up key core activites, in just four years, we have shifted the situation towards a trial and experimental medicine culture in the UK. Key activities we developed & which are now valuable UK available resources: 1. Stratified cohorts: collections of patients eligible for entry into trials and research 2. Experimental trials support: a system of coordination and support to enable testing of new therapies in patients 3. Neuromuscular human cell biobank: collecting muscle cells from patients to test new therapies 4. MRI biomarker studies: using MRI scans to accurately measure muscles and assess if experimental treatments are working 5. Training programmes to train more young scientists to undertake trials and develop new therapies 6. Getting clinicians & animal scientists working closely together to work out which are the best cell & animal models on which to test new therapies These core activities & our clinician scientist networks have resulted in a ten-fold increase in clinical trials & an even larger increase in patients entered into research cohorts. We now want to build on this success to embed a trials culture in UK practice. In the UK there is no other centre that focuses on systematically linking discovery research to experimental medicine for NMD. This MRC Centre has lead the UK efforts in the last four years. The mission of a renewed MRC Centre is to achieve impact by translating science into experimental medicine & find treatments for adults & children with disabling/fatal neuromuscular diseases.

The UK Longitudinal Linkage Collaboration (UK LLC) has been set up to bring together data from longitudinal study participants with their routine records. This is done in a secure way to help researchers work to improve health and wellbeing throughout and beyond the COVID-19 pandemic. What does this mean and why is it important? Longitudinal studies gather data about people's lives over time. This data can lead to discoveries that improve people's lives. Linking study data with health and administrative records will help researchers deliver public benefit research. Continued funding of UK LLC will allow us to use what we learned from the pandemic and offer the resource as a long-term service for UK longitudinal research. It will make possible research into our biggest health/socio-economic challenges and widening health inequalities. The large scale, diverse linked data will provide the numbers for researchers to study rarer outcomes and harder-to-reach populations. How does UK LLC work and how is it unique? UK LLC will support a national move to standardise and regulate data access for all Longitudinal Population Studies (LPS). We are a national Trusted Research Environment (TRE) for longitudinal research. A TRE is a secure computer system that allows researchers to analyse data from within the environment. Our TRE holds data from 280,000 study participants from across the UK. The data itself is held within the TRE - it never leaves, and it's never sold on. Data is linked to regularly refreshed NHS and environmental records (eg, air pollution, noise pollution). We have secured approvals to link to employment, earnings, benefits and education records from the UK Government organisations who own this data. We are working with studies to make sure participants are aware of this use of their data and can discuss any concerns with their study team. We know that some studies may choose not to permit all linkage options. This new resource has been made possible by providing an easy and consistent way for studies to join and by centralising our operations. Our processes were built from the ground up with particular focus on safeguards and security. Who is involved in UK LLC? Our partnership includes UK LLC, lead researchers from 24 studies and many other key individuals and organisations working with health data. We will support parts of the UKRI Population Research UK (PRUK) vision to centralise support for studies. This will unlock new scientific opportunities. We have public contributors, including study participants, who form an important part of our existing and planned activities. They focus on representing the views of publics and study participants, working to make sure the way we talk and promote the resource is transparent, clear and demonstrates the public benefit. What will this funding allow UK LLC to do? It will allow us to continue to offer this valuable national resource for research and to make it better. It will enable UK-wide analyses, allowing research results and effects on policies to be measured and compared. We will quickly be able to bring on new and existing study data. As researchers use the resource, it will create an ever-increasing knowledge base to build and improve on. Importantly, we will be able to learn from the coronavirus pandemic and use the TRE to support a quick response to future crises and NHS/UK Government needs. Continued funding will deliver our three core objectives to a) make UK LLC a globally unique resource in the breadth and depth of its capability, b) provide a route for studies to move to working with their data in TREs and c) empower researchers to get the best out of the available data and continue to build and grow its capacity and improve its quality as a high value research resource for the UK. By bringing this data together, we're providing a way for research to meet the needs of people across all our communities.

a. aim(s) of the research: It seems that some children and young people (CYP) remain ill for a long time after infection with COVID virus. They are said to have ‘long COVID’. Something similar can follow a common childhood infection called glandular fever. Doctors don’t know how to diagnose long COVID, how common it is or how long it goes on for. There is no simple test for long COVID. We need to know more about it if we want to treat it. b. background to the research: Little is known about long COVID in adults or CYP. Risk factors for worse COVID in CYP include obesity, pre-existing diseases, learning disabilities, diseases of the brain, mental health problems and coming from an ethnic minority. The CYP likely to be most at risk of long COVID are teenagers who are more at risk of persistent fatigue and mental health problems after other viral infections. c. design and methods used: We will approach 30,000 CYP, half of whom we know had COVID. We expect 6,000 to agree to help us and we will ask them whether they still have physical or mental problems at 3, 6,12 and 24 months afterwards. We can compare the 3,000 responders who had a positive COVID test with the 3,000 responders who didn’t test positive. We can then agree on what is a medical diagnosis of long COVID and how we might treat it. d. patient and public involvement: (PPI): We will have a paid PPI lead who will ensure co-production with carers and CYP. We will also use some funds to encourage busy carers and CYP to give their valuable time to complete the survey s.e. Complete transparency: We will share all our results ASAP for free with anyone who wants to see them, especially the CYP who take part.

Childhood arthritis, classified under the umbrella term juvenile idiopathic arthritis, JIA, and its associated eye inflammation, JIA-uveitis, can be devastating for both child and family, and impose significant long-term economic burden on society. Despite improvements in the management of JIA, and increasing availability of new medicines, many children still undergo prolonged treatment with multiple drugs that may not work, leaving them exposed to uncontrolled inflammation, side effects, and the damaging effects of disease, which include disability, vision loss, lower quality of life and reduced chances of employment. Early control of childhood arthritis and JIA-uveitis translates to better longterm outcomes and economic benefit. However, current JIA classification does not inform choice of drug for most children, and there are no verified clinical or biological tools with which to predict disease course, select treatment or predict response. Effective strategies allowing doctors to choose the right medicine, at the right time for each child ('stratified medicine'), would increase early remission rates, reduce suffering, improve long-term outcomes and avoid years of treatment with ineffective drugs. To start to address these unmet needs, we established a partnership between 4 large UK JIA cohort studies, the Childhood Arthritis Response to Treatment (CHART) Consortium, representing 5000 children with JIA, with clinical information, biological samples, and new data. Building on our success, and strengthened by important new cohorts and investigators, we now propose an ambitious consortium, CLUSTER, bringing together internationally recognised leaders in childhood arthritis and JIA-uveitis, with new collaborators and industry partners to deliver stratified medicine for JIA. CLUSTER will include multidisciplinary expertise in clinical, molecular, genetic, immunological, and statistical sciences, with UK leaders in paediatric rheumatology and ophthalmology, and those designing and delivering clinical trials in JIA and its associated uveitis. The overall goal of CLUSTER is to define 'endotypes' (subgroups based on underlying disease mechanism) of childhood arthritis and JIA-uveitis, which more accurately reflect likely treatment response and disease course, linked to biomarkers that are feasible to measure in children, to allow targeted treatment decisions. We will adopt a P4 (predict, prevent, personalise, participatory) approach; our key scientific aims are to: 1. Identify 'biomarkers' (clinical, genetic, protein, gene expression or immune factor) that help predict treatment response in JIA, to allow a more targeted approach to medicine choices and prevent poor long-term outcomes; 2. Identify predictors (clinical, genetic, auto-antibody) of getting uveitis for children with JIA, to improve screening protocols and prevent vision loss; 3. Using specimens from both blood and inflamed joints, undertake state of the art analysis of cells, proteins and gene expression in JIA to define mechanisms of response to treatment and different disease types, and identify new treatments; 4. Integrate and explore all CLUSTER data together to define endotypes in JIA, that predict disease type or treatment response, with associated markers that can be measured, to enable personalised treatment and facilitate patient/parent participation in treatment choices; 5. Establish collaborative agreements with Industry and international partners to ensure that high-quality bio-sample collection and stratification design are used in future trials in childhood arthritis and uveitis. Our programme of work will speed up the introduction of 'stratified' medicine for children with JIA. Earlier control of inflammation and reduced exposure to side effects will allow children to return to their education and full sporting and family life activities, prevent life long disability and blindness, and reduce costs to the health service and society as a whole.