Cardiovascular diseases (CVDs), such as strokes and heart attacks, are the leading causes of death amongst women globally. A particular group of women at high risk of cardiovascular disease are those who experience a pregnancy complicated by gestational diabetes mellitus (GDM) and/or a hypertensive disorder of pregnancy (HDP). Following a pregnancy affected by GDM, within 5 years up to 50% of women will develop T2DM; and following HDP, 30% of women will develop hypertension. Both these conditions greatly increase risk for CVD, however with timely detection and management these risks can be greatly reduced. The importance of breaking this link between high-risk pregnancy and CVD is widely acknowledged, yet to date there have been no trials demonstrating this can be achieved, and importantly whether it can be done affordably and at scale. Three key actions are needed: (i) effective primary prevention; (ii) regular screening, and (iii) evidence-based management when disease is detected. India is experiencing an epidemic of type 2 diabetes mellitus (T2DM) and hypertension. 73 million people have diabetes, and 207 million hypertension (2017 data). Rates of GDM and HDP are high, affecting 20% and 10% of pregnancies, respectively. There is an urgent need for effective and affordable preventative strategies to reduce the economic, social and health consequences of these conditions for women in India. In the UK, GDM and HDP are the commonest complications of pregnancy. After a pregnancy with GDM, women should undergo screening with their GP 6 week after birth for persistent high blood glucose. Attendance however is generally poor, with rates between 30-70% across the country. Following HDP, evidence is needed to guide care. The Fellowship will enable me to lead connected programs of work across two countries: India and the UK, determining the role digital innovations could play to deliver post-partum interventions in women globally. I will conduct two clinical studies, with active engagement with policy makers, clinicians, digital health companies and social enterprises throughout the Fellowship. SMART Health is a digital platform, developed by the George Institute for Global Health, that has been implemented in India, Indonesia, China, and Myanmar, to improve detection and management of diabetes and hypertension. The platform is aimed at rural community health workers and primary care doctors, enabling task shifting, clinical decision support, automated referral, SMS reminders, and patient tracking. Since 2017, I have been leading the group adapting this platform to improve the detection and management of anaemia, GDM and HDP in pregnant women living in rural India: SMART Health Pregnancy (SHP). Through this Fellowship I will extend SHP to facilitate prevention, screening, and early treatment of hypertension and T2DM in the years after a pregnancy complicated by GDM and/or HDP. The effect of this on achieving target blood pressure and blood glucose control after high risk pregnancy will be assessed in a large clinical trial in rural India, following 960 women for 5 years. In the UK, I was part of the team of clinicians and researchers in Oxford who developed a remote monitoring system for women with GDM (GDmHealth). We demonstrated in a clinical trial that this approach was safe, convenient and preferred by women and health workers. The technology was licensed to a commercial company (Sensyne) in 2018, and since then thousands of women have benefited from this innovation across the UK. Through this Fellowship I will lead a program of work adapting this approach for women in the year after birth, assessing whether remote monitoring improves screening attendance, deliver effective lifestyle support, offer a potential cost savings to the NHS, whilst being acceptable and more convenient for new mums. Theis approach could improve their health, for future pregnancies and lifelon

NICE requires research to help it decide which treatments and diagnostic methods should be funded by the NHS. NICE has highlighted the need for research into the methods for reviewing evidence from research. Identifying research studies underpins most NICE reviewing. Methodological search filters are widely used to identify specific research designs such as randomized controlled trials or economic evaluations. Search filters are carefully selected collections of words and phrases used to search databases to identify research. Little is known about how well search filters work in finding research. This means that their use as a standard tool for NICE researchers may not be informed by adequate information to indicate how search filters perform across different subjects, questions and databases. Our proposal is to investigate how search filter performance can be measured and what measures are most useful to researchers. We also plan to investigate systems and approaches to provide better access to relevant and useful performance data on methodological search filters. The benefits of this research would be to enhance the tools and knowledge of the tools available to find research evidence to inform NICE appraisals, guidelines and other guidance. The research findings would also benefit other national technology assessment agencies, guidelines groups and related bodies.

Earlier detection is a high priority for patients and improves survival: 84% of people with myeloma survive for >5 years if diagnosed at the earliest stage, compared with only 26% if diagnosed at advanced stage. Myeloma is most frequently diagnosed late (>3-6 months post symptom presentation) and has the longest diagnostic delay of any cancer, with emergency presentations in >30% of newly diagnosed myeloma patients who have shortened survival, cancer arising from bone marrow, is the 20th most common cause of cancer deaths worldwide and remains incurable. Myeloma (MM) is often diagnosed at an advanced stage when it has multiple effects on patients' overall well-being, including bone disease, kidney disease, and a weakened immune system. Recent treatments have improved life expectancy and quality of life. The earlier that myeloma is diagnosed and treated, the more effectively symptoms are controlled, improving patient survival and reducing healthcare costs associated with treating late-stage myeloma and attendant co-morbidities. Every myeloma arises from a preceding, often symptomless and undiagnosed condition called Monoclonal Gammopathy of Undetermined Significance (MGUS), occurring in ~3% people aged 50 years and over. Screening >50s for MGUS and monitoring for progression using the existing inexpensive diagnostic blood test would enable myeloma early diagnosis but is unlikely to be cost-effective as most people with MGUS do not develop MM. Monoclonal gammopathy of clinical significance (MGCS) is a recently coined termed to capture a set of monoclonal gammopathy patients who have kidney impairment, nerve damage, bone fractures or skin lesions directly linked to the presence or deposition of the monoclonal protein. Lack of recognition of this clinical association leads to diagnostic delay and irreversible damage to organs involved. Therefore, we aim to specifically identify MGUS patients at high risk of progression to myeloma and / or MGCS. Objective 1: Understanding the symptom burden, and additional clinical parameters driving the test request, which lands an incidental diagnosis of MGUS is key. Using access to Clinical practice research data link (CPRD) primary care records on patients coded as monoclonal gammopathy to generate this dataset. We will identify set of predictors for transformation from MGUS to MM. CPRD data will also enable identification of clinical associations recently described as MGCS conditions. Objective 2: Oxford University Hospital, we have recently established the OxCom clinical service funded by Oxfordshire Clinical Commissioning Group to improve serial MGUS monitoring for patients in the Oxfordshire community. This funding has been allocated to address the lack of serial follow up of MGUS patients; patients are often lost to follow up, and GPs' are unable to address clinical concerns generated by MGUS patients in primary care. This OxCom infrastructure enables us to generate a prospective dataset with detailed clinical and laboratory data. Hypothesis generating observations generated from the CPRD datasets can be validate in this prospective MGUS database. We will validate the primary care prection model in the OxCom database. Objective 3: Recent observations have shown that aberrant changes to light chains secrete dby MGUS patients can help predict who would develop MGCS, and/or potentially transform to myeloma. Working with Department of Chemistry at Oxford we can prospectively evaluate these preliminary observations in the surplus patient samples obtained from the OxCom service. These shared research-enabling resources will help drive improvements in early diagnosis and MGUS/myeloma care in the NHS. My vision is to harness the multidisciplinary expertise in Oxford across big data analysis (primary care data), joined up secondary care clinical services and protein chemistry expertise to improve monitoring of MGUS patients, and enable early diagnosis of MGCS and myeloma.

For older adults, exercise improves fitness and health, maximises participation, increases functional independence and enhances quality of life. Higher fitness-levels are linked to lower levels of emotional distress and depression, improved mobility, functionality and independence encouraging a higher level of behavioural activation and social inclusion Adherence and compliance with recommended exercise guidelines remains poor amongst ageing adults who frequently avoid participation for fear of falling, exacerbating symptoms or provoking pain or fatigue. The shortage of appropriately qualified trainers means some institutionalised elderly are sedentary for over 12 hours a day, their only energy expenditure being when getting in and out of bed. We have created a series of bed and chair-based programs for older adults, some of whom may be resistant to exercise, providing a graduated course of physical activity suitable for everyone, from the very frail to the healthy agile. We will engage older adults who may be isolated, bedbound, frail, have multiple health conditions, physical disabilities, learning difficulties or mental health issues, and lead them through specialised bed and chair-based exercises given remotely, linked by a live-stream platform such as Webinar or Zoom, presented on large-screen TV, through their own smartphone, tablet or laptop enabling everyone to work in a group. The sessions will be supplemented by videos and an App. During the next 12 months we will complete the filming, select the live-stream platform and test the system in community settings with the aim of producing a solution ready to roll out to the Care Home sector.

Around a quarter of patients with the most common cause of thyroid gland overactivity (Graves' disease) develop a complication known as Graves' orbitopathy (GO). In GO, tissues in the space behind the eyeballs (the orbit) become inflamed, causing pressure to build up. This causes intense pain, restriction of eye movements, and in some cases permanent damage to sight. The pressure causes the eyeballs to bulge forward (proptosis), causing a startled, staring appearance which is disfiguring and a cause of great psychological harm (at least a third develop significant depression and anxiety). Following an initial highly active phase, patients with GO develop long lasting changes in the tissues of the orbit, which means the eyeballs remain projected forwards. Patients may be treated with high doses of steroids, and some require surgery to decompress the orbit, both to save sight and also to improve the appearance of the eyes. It is well established that antibodies targeting a receptor which stimulates the thyroid gland are the cause of its overactivity in Graves' disease. Whilst this antibody is also important in GO, the majority of GD patients do not develop this complication. Why this might be is unknown. We also don't know if different antibodies are important in GO, and whether they are made by inflammatory cells local to the eye. The reason some patients develop long term disfigurement is also not understood. In this project, we will use advanced techniques to analyse the makeup of the inflamed orbit, one cell at a time, from samples taken during decompression surgery. We will look at the antibody producing cells in the orbit and compare them to those in the blood, to see whether they are likely to be driving the disease. We will also look to see how the cells in the orbit are different between the initial and long term phases, and if there are subsets which may be responsible for this progression. Finally, we will perform experiments to see how antibodies and other inflammatory molecules cause changes in fibroblasts, important structural cells of the orbit.