NIHRDataInsights/HRCSData huggingface dataset:
Award Title: Improving cancer prevention, risk-stratification, and detection using large-scale prospective studies in diverse populations - Studentships
Funder: Cancer Research UK

Abstract: Background 
We have established, in China and the UK, some of the world’s largest prospective cohort studies. Their size, maturity, differing exposure patterns and ranges, and availability of genetic and biomarker data, provide an unprecedented opportunity to further advance our knowledge about causes of cancer in diverse populations, leading to improved strategies for prevention, early-detection and management.
Aims
Building on previously funded work, we aim to bring together the Million Women Study (MWS) and China Kadoorie Biobank (CKB), along with UK Biobank (UKB), to: (i) investigate the causal relevance of major modifiable risk factors (e.g. infections, adiposity, physical activity and diet) for cancers and important subtypes, and explore potential mechanisms and gene-environment interactions; (ii) assess the role of pre-existing morbidity in cancer incidence and detection; (iii) quantify breast cancer risks associated with clinical factors and develop risk stratification tools for breast and other cancers; (iv) assess the feasibility of large-scale recruitment and blood collection into a new MWS sub-cohort for validation of novel methods for early detection of cancer.
Methods
The MWS and CKB include more than 1.3 and 0.5 million participants, and, by 2023, will have ~200,000 and ~40,000 incident cancers. Integrated analyses in both cohorts, and in UKB, will utilise the vast array of exposures, many similarly recorded across studies, and well-phenotyped outcomes with unprecedented power to analyse cancers of unmet need (totalling e.g. 8000 oesophageal, 9000 pancreatic, and 7000 liver cancers). Evidence for mechanisms and causality will be assessed using available multi-omic biomarker and genetic data. In CKB, associations with 16 infectious pathogens will be examined in a case-cohort study of ~30,000 cancers and ~10,000 controls. In the MWS, the predictive value of breast density and other features will be investigated using ~500,000 mammographic images. Modelling of the joint effects of risk factors will provide estimates of absolute risk for specific subtypes of breast (ER-positive, triple-negative), and other cancers. Pilot studies of blood collection methods, and estimation of response rates, will inform protocol development and a future funding application for the proposed MWS sub-cohort of ~200,000 women.
How the results of this research will be used 
Our findings will inform global cancer prevention strategies, elucidate mechanisms, and enable identification of individuals who may benefit from targeted screening and preventive interventions. The new data collections will represent valuable resources for data sharing and future studies of machine-learning based predictors, omics-based biomarkers, and validation of early diagnostic tests.


Research Activity Codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health Categories: CANCER AND NEOPLASMS
Award Title: Improving early detection and diagnosis of breast cancer among multi-ethnic rural communities in Malaysia - implementation of the CENP
Funder: Medical Research Council

Abstract: Phase 1 will involve conducting an evidence synthesis of studies about community navigation programmes. The views of community advocates and stakeholder groups will be elicited via focus groups with women from different socioeconomic backgrounds and ethnic groups in rural areas of Segamat and individual interviews with key informants. Phase 2 will involve co-designing a culturally sensitive CENP, the selection of navigators and the development of training modules and health education materials. Phase 3 will test the appropriateness and acceptability of the new programme via FGs. Phase 4 will conduct a comparative evaluation in Segamat district which has 11 sub-districts, 5 of which provide data for the SEACO platform. The 5 sub-districts are approximately similar in terms of socio-demographic profile and health service profile. One intervention sub-district and two comparator sub-districts will be chosen randomly from the 5 rural sub-districts. SEACO completes an annual enumeration and multiple population-wide health surveys in these sub-districts. A sample of 466 at the 'intervention sub-district' and 466 at each 'comparator sub-district' will be drawn randomly from SEACO data to participate in the evaluation. A sample size of 1400 will allow 80% power to detect, as statistically significant at the 5% level, an increase of 8% or more in the proportion aware of a breast cancer symptom in the CENP site compared with comparator sites after the intervention (based upon baseline awareness of a breast lump as a cancer symptom of 65% from our previous Newton-funded study). The sample size of 1400 will also allow 80% power to detect an absolute increase in the proportion of women who visit a doctor in the 6 months following CENP of 8% in the CENP site compared with comparator sites. Phase 5 activities will involve dissemination and writing joined-up policy and practice briefs for the Ministry of Rural Development and the Ministry of Health.


Research Activity Codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health Categories: CANCER AND NEOPLASMS
Award Title: Improving empiric antibiotic prescribing by applying a Bayesian decision theory approach to phenotypic and genomic resistance data.
Funder: Medical Research Council

Abstract: The aim of this project is to provide a Baysian predictive tool that can be used by clinicians to decide on the best empiric choice of antimicrobial (AM) in a variety of clinical scenarios. The basis of this model will be phenotypic antimicrobial resistance (AMR), patient outcome, and whole genome sequence data for bloodstream infections. Severn pathology lab and Winpath LIMS serves 3 NHS trusts generating  about 2000 Gram-negative isolates per year from blood cultures with associated AMR and outcome data. We will collect up to 1000 of these isolates. Using the data extracted from LIMS, clinical, biochemical and microbiological data can be associated with each sample's unique identifier. These isolates will be sent in batches for WGS to the MicrobesNG facility in University of Birmingham. We will receive monthly data report on blood cultures sent from hospitals sharing Winpath LIMS. We will use the data within the R statistics environment to apply a Bayesian predictive modelling approach with Bayesian network decision theory to our local phenotypic AMR data. We will derive predictive probabilities for resistance and outcomes by assessing the extent of correlations at multiple levels: a) to derive estimates of co-resistance between AMs; b) to model correlations with metadata; c) to understand temporal effects on the model. Following collection of the WGS data and completion of the initial model we will compare our predictive model to our genomic data and integrate these results into our final model. This will be piloted at University Hospitals Bristol NHS Foundation Trust to assess and improve usability in a real-world context..


Research Activity Codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health Categories: INFECTION
Award Title: Improving haematopoietic reconstitution in blood stem cell transplantation procedures through the regulation of stem cells and their niches
Funder: Medical Research Council

Abstract: Haematopoietic stem cell (HSC) transplantation (HSCT) is routinely performed in patients with haematological, genetic or metabolic disorders. Regenerating haematopoiesis after HSCT requires: 1) harvesting sufficient donor HSCs, 2) optimal HSC homing to the bone marrow and 3) expansion and differentiation of donor HSCs in the recipient. However, HSC engraftment efficacy significantly decreases during ageing and in certain haematological diseases, hampering the use of HSCT as a therapeutic option. Among different HSC sources for transplantation, umbilical cord blood (CB) is an ideal source that can be non-invasively harvested, cryopreserved and is associated with reduced risk of disease transmission or acute graft-versus-host disease. However, several CB units are necessary for transplantation and engraftment is delayed. This proposal aims at understanding and modelling the regeneration process following HSCT. The main goal is to identify cell-intrinsic and -extrinsic mechanisms that regulate HSC proliferation and lineage commitment during bone marrow regeneration. Our translational aim is instructing HSC to more efficiently/rapidly/long-lastingly regenerate the haematopoietic and immune systems. We will use xenografts and ectopic bone ossicles to model human HSCT in a humanised niche environment. Human cells will be analysed by 10x scRNA-seq and scATAC-seq to generate a cell-cell communication network between human HSCs and niche cells. Metabolic profiling (glycolysis, OXPHOS, mitochondrial activity, ROS) will be complemented with and Mass Cytometry and imaging studies. Finally, the role and potential of novel regulators of HSC quiescence and emergency haematopoiesis will be tested. The complementary expertise of the four teams in the cellular and molecular heterogeneity of human HSCs, their regulation through inflammatory factors, cellular metabolism and microenvironmental cues could facilitate overcoming current limitations in HSCT.


Research Activity Codes: 5.2 CELLULAR AND GENE THERAPIES
Health Categories: BLOOD
Award Title: Improving mental health for marginalised groups at Oxford's Wellcome Centres
Funder: Wellcome Trust

Abstract: This proposal will address the intersection of mental health and Equality, Diversity & Inclusion (EDI) within Oxford’s three Wellcome Centres. Mental health concerns permeate a broad range of challenges relevant to EDI, including social exclusion, chronic illness and disability, and minoritised populations (detailed below) that are disproportionately affected by mental ill-health.
 
By identifying specific mental health challenges that different groups face, we can improve equality. Through normalisation of discussions around mental health in the workplace, and building an appreciation for how these issues affect people differently, we foster inclusion. If we can recruit and retain a broader range of researchers further into their careers, we improve diversity, and therefore our science. An increasingly inclusive, fair and kind research culture will lower the risk of mental ill-health for all our team and staff members within the high-impact but high-pressure academic environment.
 
Our specific objectives are to:
(i)  Conduct an in-depth, expert review of mental health as it relates to EDI within our Centre work environments.
(ii)  Implement recommendations arising from this review relating to policies, communication and practices.
(iii)  Build a broad, cross-Centre programme promoting positive research change around mental health and EDI.


Research Activity Codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health Categories: GENERIC HEALTH RELEVANCE;MENTAL HEALTH
Award Title: Improving our understanding of e-cigarette and refill packaging in the UK (E-PACKS): How is it used for product promotion, how is it perceived by consumers, and could it be changed to discourage youth while encouraging adult smokers to quit?
Funder: Cancer Research UK

Abstract: Background: There is limited research on e-cigarette packaging and labelling, particularly in comparison to cigarettes. Few studies have explored how e-cigarette packaging is being used by manufacturers to promote these products, whether the product information on packs complies with current regulations, and consumer perceptions of the warnings and messaging on e-cigarette packs.

Aims: The project aim is to determine whether further regulations on e-cigarette packaging are needed in the UK and, if this appears to be the case, provide recommendations to help the UK Government in developing guidelines that help make e-cigarette packaging more appealing to smokers and less appealing to young people and non-smokers.

Methods: Two studies will be conducted. The first will be a systematic analysis of e-cigarette packs currently on sale in the UK to document the types of pack design and promotional features used and to assess whether the packaging of e-cigarettes and refills in the UK complies with current regulations. The second study will involve sixteen focus groups in England and Scotland to explore how young people (11-17 year olds) and adults (non-smokers, smokers who do not use e-cigarettes, and smokers who do use e-cigarettes) view e-cigarette packaging, including flavour descriptors and health messaging, and their views on alternative health messages and possible further regulations on e-cigarette packaging. 

What value will the programme of work deliver? The work will help improve our knowledge of e-cigarette and refill packaging in the UK, including how is it used for product promotion and perceived by consumers. It will also allow an understanding of whether the pack could be used to promote healthier choices among smokers while protecting non-smokers.


Research Activity Codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health Categories: CANCER AND NEOPLASMS
Award Title: Improving sleep and circadian disruption in Dementia
Funder: Medical Research Council

Abstract: The UK Dementia Research Institute (UK DRI) is an initiative funded by the Medical Research Council, Alzheimer's Society and Alzheimer's Research UK.  Funding details for UK DRI programmes will be added from 2020. A common symptom for people living with dementia is disturbed sleep. However, there is still little known about whether sleep is just a consequence of dementia, and therefore could be utilised as an indicator of early disease, or a driver in pathogenesis of the disease. Both these explanations may be true but either way, there is a wealth of knowledge still to uncover in this field.  This UK DRI programme will validate and develop technology to quantify vigilance states, sleep symptoms and physiology across the 24-hour day (i.e. circadian rhythm).  The team will validate the new technologies developed under rigorous sleep lab conditions prior to testing in the home environment. Main objectives and research goals: 1. To validate and implement technology to characterise circadian and sleep disturbances in the home that can be scaled to be used in dementia and its preclinical phase. 2. To develop and validate approaches to integrating sleep and circadian disturbances with other sensor information to predict variation in behavioural and cognitive symptoms, and clinical events such as falls and disease progression. Four parallel research strands will be pursued: 1. Circadian Assessment: The team will validate accelerometers as a low-cost approach to assessing circadian sleep rhythms in order to facilitate their use in the monitoring of large populations and the evaluation of interventions. 2. Home EEG monitoring: The team will evaluate devices capable of prolonged (ideally 24 hours) home EEG recording. Requirements to be met are the accurate assessment of sleep stages (REM and NREM), sleep continuity and EEG features during sleep and wakefulness. 3. Contactless sleep and circadian assessment: In addition to the focus on wearable technology, they will develop passive monitoring for sleep and circadian rhythm that can be scaled independently of patient compliance. They will evaluate passive approaches to sleep assessment using movement sensors attached to beds and sheets, automated video analysis and integration of multi-modal data produced by a ‘Healthy Home system’ including home radar. 4. Technology evaluation: New technology will be evaluated in the Living Home, part of the Clinical Research Building at the University of Surrey.


Research Activity Codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health Categories: NEUROLOGICAL
Award Title: Improving the diet of pregnant women: a mixed methods study
Funder: Medical Research Council

Abstract: There are two UK dietary guidelines for pregnant women that aim to minimise ingestion of toxic metals, which flow freely through the placenta to the fetus with adverse effects on neurodevelopment. The guidance is not informed by up-to-date data on dietary intakes and exposure levels, nor has there been any evaluation of the effectiveness of current guidance.  A mixed methods observational cohort study of 400 healthy primigravid women will: (1) evaluate understanding of the UK guidance on fish and game/gamebird consumption in pregnant women and midwives; (2) compare dietary intakes with the guidance; (3) measure blood lead and mercury and urine arsenic concentrations; (4) estimate the contribution of diet to the biomarker concentrations. This will be achieved by quantitative assessment of dietary intakes with food-frequency questionnaires at 10- and 28-weeks' gestation and opportunistic blood and urine sampling at the same times through community antenatal clinics. Qualitative interview group studies with pregnant women will enable evaluation of knowledge and impact of the guidance. A questionnaire will be used to establish knowledge of the guidance by midwives, and how and when they disseminate information, with further in-depth data collection through qualitative interview groups. The research will provide an evidence-base for clarification and effective dissemination of dietary guidance related to toxic metals to enable women to make informed choices about their diet with optimisation of the health and development of the baby.


Research Activity Codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health Categories: REPRODUCTIVE HEALTH AND CHILDBIRTH
Award Title: Improving the outcome of children with congenital athymia.
Funder: Wellcome Trust

Abstract: Congenital athymia causes life-threatening T-cell immunodeficiency. The only definitive treatment is thymus transplantation (TT). Despite lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus, repopulated by recipient bone marrow-derived lymphoid progenitors, supports functional T-cell development restricted to host MHC alleles. Though lifesaving, TT results in subnormal circulating T-cell numbers and frequent autoimmune complications. I aim to dissect the cellular and molecular mechanisms of lympho-stromal crosstalk and thymopoiesis in the context of MHC-mismatched TT by using single-cell and spatial genomics on pre-transplantation cultured thymic tissue and post-transplantation graft biopsies. Donor thymocytes, possibly including long-lasting lymphoid progenitors, remaining at the time of transplantation despite lympho-depleting preparatory culture, may contribute to this crosstalk and assist thymic epithelial cell (TEC) homeostasis. Other recipient-derived haematopoietic cells may migrate into the graft to replace direct interactions between developing host thymocytes and TECs. Alternatively host TECs may develop in the transplanted thymus. I hypothesise that partial MHC-matching improves crosstalk signalling, achieving better immunoreconstitution and less autoimmunity. Optimising in vitro differentiation and maturation of TECs derived from pluripotent stem cells will make the in-depth investigation of MHC-TCR interactions and downstream signalling possible. New insights into TEC biology will advance alternative approaches to thymus replacement therapy.

Lay Abstract: The thymus gland produces white blood cells, called T-cells, an essential part of the immune system. Infants born without a thymus (athymia) lack T-cells, are extremely vulnerable to infections and may die. Thymus tissue necessarily removed from otherwise healthy infants during surgery for heart defects can be grown in the laboratory and transplanted into athymic infants. Although the tissue type of these infants is not matched with the thymus they receive, transplanted patients can fight infections and survive. However, T-cell numbers rarely reach normal levels and sometimes these cells mistakenly attack the patient’s own body causing autoimmune complications. This may be due to lack of tissue-type matching. Using new research techniques to investigate how non-matched thymuses can support T-cell development and the mechanisms underlying complications, I aim to gain fundamental insights into thymus functioning, paving the way for the development of alternative treatment approaches to improve patient outcomes.

Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: INFLAMMATORY AND IMMUNE SYSTEM
Award Title: Indigenous peoples responding to Covid-19 in Brazil: social arrangements in a Global Health emergency
Funder: Medical Research Council

Abstract: This proposal is focused on indigenous peoples' response to the COVID-19 pandemic in Brazil, a country which now has the second highest number of infected people in the world (2,962,442 cases by 7th August). In the absence of clear national public-health leadership, most of the 300 different indigenous peoples are taking responsibility to contain the spread of the new coronavirus among their communities into their own hands. They are at high risk as result of recent sociopolitical developments such as mining development and migration into remote areas. In addition, it is likely that many indigenous infections and deaths remain undocumented. Using anthropological knowledge and methodology, such as rapid appraisal and participatory ethnographies which includes online interviews, documentary, bibliographic and visual data, we will identify indigenous responses and mobilisation of strategies to mitigate risk and bear witness to undocumented impact on indigenous lives. We will work closely with the Secretaria Especial de Saúde Indigena (SESAI, attached to the Brazilian Ministry of Health) seeking to cooperate with global and public health agencies and policies, as well as engage decisionmakers to shape better responses to face this outbreak. In accordance with indigenous peoples' modes of existence, we propose three programme axes to frame the research and actions: 1. Health, Care and Death; 2. Mobility and Circulation; and 3. Gender. A digital platform 'Amerindian Response COVID-19 - Anthropology Platform' will also be developed and used as a tool to publish brief reports in real time, using different media, in addition to academic papers. Monthly reports will be addressed to SESAI and eight case studies will be conducted across Brazil's regions. key lessons will be drawn to reduce transmission and impact of this and future pandemics, in this and comparable countries.


Research Activity Codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health Categories: INFECTION