NIHRDataInsights/HRCSData huggingface dataset:
Title: Reproductive Health, Nutritional Status, and Macroeconomic Shocks: A Multi-Level, Quasi-Natural Experimental Analysis of Food Commodity Prices
Funder: Economic and Social Research Council

Abstract: Global food price rises threaten to undermine progress in improving maternal and child health and nutrition. As the World Bank 2012 Global Monitoring Report titled 'Food prices, nutrition, and the MDGs' concluded "Even temporarily high food prices affect the long-term development of children...seemingly small shocks can exert great damage if they are not dealt with early." While there is strong evidence that maternal and fetal nutrition affect children's development, there is relatively little evidence linking aspects of reproductive health (e.g. breastfeeding, neonatal mortality) to the price and availability of nutritious food. Thus, our project aims to: (1) Assess the effects of food commodity prices on reproductive and child health, specifically maternal and childhood nutrition, fetal development, neonatal mortality, and early-childhood development; (2) Identify national, state and household policy responses which may mitigate or exacerbate the reproductive and child-health effects of rising food prices. To fulfil these aims, the initial phase of the project will provide a detailed qualitative and quantitative multi-level, case-study of India, which will then be extended as a cross-national analysis of Demographic and Health Surveys in 84 countries. The project will combine PopDev priority resources such as DFID Young Lives with multiple data sources and large-scale surveillance projects containing rich information on economic policy, food prices, nutrition, reproductive health. The project will build a collaborative exchange between Public Health Foundation of India (PHFI), Cambridge, and LSHTM, supported by a multi-disciplinary international advisory team. Its findings will reach a wide group of stakeholders through a proposed policy workshop and briefs at Chatham House, as well as through meetings with Indian stakeholders at PHFI, and through publications in population, development, and public health journals.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Translation of non-invasive pre-natal diagnosis (NIPD) for selected single gene disorders into a clinical setting.
Funder: Department of Health (England)

Abstract: Current prenatal genetic testing is by amniocentesis or chorionic villus sampling which each carry miscarriage risks. Recently developed tests, called "non-invasive" prenatal diagnosis (NIPD), do not have miscarriage risks. These are possible since the discovery that there is a small amount of a baby's genetic material, known as free fetal DNA, present in a pregnant mothers blood. Tests for some genetic disorders, such as the muscle disorders Duchenne and Becker muscular dystrophies, are currently being developed. However because there are thousands of different genetic disorders, many extremely rare, it is challenging to make these tests available to a wide range of different families. Scientists must show that the NIPD tests are accurate on stored blood samples for a range of conditions and then show that the tests are possible in the antenatal clinic and provide the same accurate results. Once proven the tests can be considered by the UKGTN (UK Genetic Testing Network) for implementation into routine NHS service. This project would accelerate the safe transfer of genetic research into improved patient care for many different genetic disorders. Removing the miscarriage risk with the introduction of NIPD will increase the acceptability, and therefore availability of prenatal genetic testing for many couples.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Assessing the potential of restorative approaches in work with families es
Funder: Health and Care Research Wales (Welsh Government)

Abstract: This research project will investigate the use of family-focused concepts and approaches in the Family First (FF) programme in Wales. The study will then proceed to explore the innovative use of Restorative Approaches (RA) as a framework for family- service provision in one local FF agency, and compare it’s efficacy to other evidence based family-focused methods and practices. FF is a new programme offering multi-agency family services throughout Wales via agencies set in every local authority. Each agency is mandated to tailor services to meet local need, and although this has created some inter-agency service variation, over-riding FF principles demand all agencies use family-family focused approaches and methods within practice. Although local agency plans show wide adoption of methods based on concepts associated with effective family-focused service provision, a few agencies plan to provide services embedded in a RA framework using RA skills. RAs stem from the same conceptual roots as restorative justice. RAs seek to address challenging behaviours and the needs of affected individuals through skills such as restorative discussions, mediation, family circles and restorative conferencing, set within organisations governed by holistic restorative values and principles. To date, RAs have achieved positive outcomes in many contexts including education and children’s residential services but, despite recognition that RAs could enhance family-service provision, very little research has been done in this area. The study will have three phases. Phase 1 will map and categorise the family-focused approaches and interventions utilised by FF agencies across Wales. Phase 2 will explore and compare the implementation of such methods, assess how family-focused they are in practice and how this affects service provision, receipt and family functioning. Phase 3 will investigate the holistic adoption and diffusion of RAs within Cardiff FF and how families receive and engage the RA as used by Cardiff FF. This phase will address a research gap by exploring the use of RAs in family service provision and their potential for application in further social care and other services.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Health Services that Deliver: Improving Care for Sick Newborns (HSD-N)
Funder: Medical Research Council

Abstract: A set of key health system challenges undermine newborn survival in low-income settings. These include limited access to quality care for sick newborns requiring inpatient services 24 hours a day throughout lengthy admissions and inadequate availability of appropriately skilled human resources. In three phases of work we will build on existing activities including formative ethnographic work to help understand nursing culture in hospitals and identify initial stakeholders and work to develop national neonatal guidelines to define core standards for care of sick newborns in hospitals. The second phase will begin with a formal stakeholder analysis and then comprise a set of distinct but inter-linked research activities using complementary approaches spanning different disciplines that address major thematic questions: 1. Epidemiology: What is the gap between capacity for providing an essential package of services for sick newborns and the likely magnitude of 'need' for this package (Gap 1)? 2. Ergonomics: What nursing time and skills are needed for effective delivery of interventions, are there gaps in the quantity or quality of tasks performed that place newborns at risk (Gap 2)? 3. Organisational science: How should context, including barriers, enablers and the cultures of facility based health worker teams guide possible task-shifting strategies? 4. Policy: Is task-shifting acceptable at regulatory, professional, team and user levels, in what forms and what are the implications for production and oversight of such service providers? Throughout this phase of work stakeholders will be regularly engaged to discuss research designs and progress and to share their thinking on the implications for workforce planning and task-shifting, process itself studied in a form of action research. In the third phase we will use illustrative economic models to help identify workforce interventions to optimize coverage with high quality neonatal care with key stakeholders.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Regulation of meiotic chromosome segregation by post-translational modifications
Funder: Medical Research Council

Abstract: Defects in meiosis lead to gametes with an incorrect number of chromosomes and this is one of the leading causes of miscarriage and birth defects in humans. In order to better understand how chromosomes segregate during meiosis, I will address the role of post-translational modifications during meiotic chromosome segregation using the model organism C. elegans, an important system for addressing the fundamental events of oocyte meiosis. In C. elegans oocytes, three structures are important for chromosome behaviour: a ring-shaped structure within the bivalents (Ring Complex), kinetochores, and spindle poles. Chromosomes achieve congression by the action of the Ring Complex while the kinetochore participates in chromosome orientation. Puzzlingly, kinetochores are not required for chromosome segregation. Thus, understanding how chromosome segregation occurs will not only be exciting to study but could also provide insights into putative 'back-up' mechanisms used in other species, including humans, to guarantee faithful chromosome segregation. The current lack of emphasizes the need for new experimental approaches. Given that Ring Complex-, kinetochore-, and spindle pole-localised proteins are actively involved in several aspects of chromosome dynamics during meiosis, it is crucial to understand their composition, structure, and dynamic regulation. This is exactly what I am proposing to do. I have recently found that sumoylation plays a crucial role during chromosome congression. On the basis of my previous results, I propose that the Ring Complex and kinetochore act as signalling hubs to guarantee proper chromosome dynamics throughout meiosis I. A key aspect I will address is how sumoylation and phosphorylation contribute to this process.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Mechanisms of lineage specification in human embryos and stem cells
Funder: The Francis Crick Institute

Abstract: The allocation of cells to a specific lineage is regulated by the activities of key signalling pathways and developmentally regulated transcription factors. The focus of our research is to understand the influence of signalling and transcription factors on differentiation during early human development. During preimplantation development totipotent human zygotes differentiate into pluripotent embryonic cells, which form the fetus, and extra-embryonic cells, which form the placenta and yolk sac. The central question we are addressing is what are the molecular mechanisms that regulate embryonic stem cell pluripotency and how is it disengaged during cellular differentiation? We seek to define the genetic hierarchy acting during differentiation, the influence of extracellular signalling and the extent to which these mechanisms are conserved between humans and mice. Towards this aim, we are characterizing the gene expression patterns throughout human preimplantation development. We are using novel genome editing technologies and modulation of signalling in human embryos with the aim of altering the expression of genes that may be important for early human development and investigating their functional role in preimplantation embryos. Using these approaches we seek to further dissect the genetic network and signalling environments that influence stem cell differentiation. This information will also be used to inform novel approaches to modulate conditions for in vitro establishment of alternative stem cells from human embryos, with the aim of expanding the repertoire of clinically relevant in vitro embryonic and extra-embryonic stem cells. The molecular basis of these early cell lineage decisions in human embryogenesis are of fundamental biological importance and have significant clinical implications for infertility, miscarriages, developmental disorders and therapeutic application of stem cells.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Harnessing cross-country administrative data to evaluate national policy impacts on maternal, infant and child health and health inequalities-MatCHNet
Funder: Medical Research Council

Abstract: The impact of fetal, infant and child health on NCDs is well-recognised. Upstream, structural factors, which are complex and inter-related, are likely to the the most fruitful for the prevention of NCDs and inequality reduction. However the evidence base to support this is limited due to difficulties in evaluating policies, which cannot be evaluated in trials. Innovations in linked, population-level administrative data (which span family members, disciplines and the lifecourse), variations between the UK countries, and continously advancing methodological options, provide unrivalled opportunities to identify which social and public health strategies are most likely to improve chronic disease and reduce health inequalities. The Maternal and Child Health Network (MatCH-Net) will develop a sustainable, multidisciplinary community of researchers and methodologists and key stakeholders: policy makers, service providers and multi-sectoral public and third sector organisations. This cross-country network is key, as data systems have evolved separately between the UK countries and policy contexts diverge with more devolution of powers. The network will lay essential foundations for future research, through three iterative objectives: 1) mapping policy variations over time and between countries and prioritising those for evaluation; 2) identifying comparable administrative data sources and indicators for national evaluation; and 3) consolidating and disseminating methods for robust evaluation of national policies. All network activities will be relevant and accessible to our key stakeholders to ensure maximum engagement of these potential beneficiaries. Network members will work together to prioritise research questions and pump prime funds will be used to pilot the most promising of these. The full funding applications that follow will request small amounts of funding to enable network activities to continue in longer term. This grant is funded by the UK Prevention Research Partnership (UKPRP) which is administered by the Medical Research Council on behalf of the UKPRP's 12 funding partners: British Heart Foundation; Cancer Research UK; Chief Scientist Office of the Scottish Government Health and Social Care Directorates; Engineering and Physical Sciences Research Council; Economic and Social Research Council; Health and Social Care Research and Development Division, Welsh Government; Health and Social Care Public Health Agency, Northern Ireland; Medical Research Council; Natural Environment Research Council; National Institute for Health Research; The Health Foundation; The Wellcome Trust.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Preventing aneuploidy in oocytes; mechanisms, markers and their potential use in clinic
Funder: Medical Research Council

Abstract: My research concerns cell cycle protein regulation in mammalian oocytes, in particular cyclin B1-CDK1 activity. In prometaphase, sufficient cyclin B1-CDK1 activity must be maintained while cells align their chromosomes. If chromosomes segregate before they are aligned, daughter cells may become aneuploid (contain incorrect chromosome numbers). Human oocytes are frequently aneuploid, this is the primary genetic cause of failed pregnancy, miscarriage and developmental disabilities in babies. My research has uncovered a novel mechanism of cyclin B1-CDK1 activity protection that prolongs prometaphase and so prevents aneuploidy in the oocytes of young mice. We find that an excess of free cyclin B1 is destroyed in preference to CDK1-bound cyclin B1 by a previously unidentified degron. Free cyclin B1 thereby acts as a decoy, occupying the cellular destruction machinery so that cyclin B1-CDK1 activity is preserved for long enough to correctly align chromosomes, preventing cell division errors in these oocytes. I aim to determine the molecular mechanism by which free cyclin B1 is preferentially destroyed, and to investigate whether this mechanism becomes compromised in aged mouse oocytes where aneuploidy rates increase significantly. I will then determine the contribution of this mechanism in preventing aneuploidy in human oocytes, using imaging mass cytometry (IMC) to simultaneously analyse cyclin B1 levels relative to proteins involved in chromosome alignment. This will reveal proteins which are aberrantly expressed in error prone oocytes, identifying potential points of intervention. In mouse I will take this further, analysing the waste polar body (PB) of the oocyte by IMC while fertilising the oocyte, relating subsequent embryo health to the protein content of the PB; developing a non-destructive protocol able to identify the most viable embryo for transfer following IVF.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Identification of key transcriptional and functional differences in adenomyotic lesions to determine novel therapeutic targets
Funder: Medical Research Council

Abstract: The aim of this project is to understand the pathogenesis of adenomyosis, identify therapeutic targets, and facilitate the development and testing of novel, fertility sparing treatments. There are 3 objectives: 1. To determine the transcriptional differences of cells within adenomyotic lesions compared with the specific anatomical regions of the correctly located (eutopic) endometrium. 2. To identify a specific panel of markers that characterise the epithelium and stroma of adenomyotic lesions, and determine their 3D microarchitecture. 3. To develop a novel in-vitro 3D culture model of adenomyosis. LCM will be used to isolate epithelial and stromal cells from the endometrium and the adenomyotic lesions, from 10 full thickness uterine wall biopsies obtained at hysterectomy from women with adenomyosis. RNA sequencing of endometrial cells from the aforesaid locations will reveal their key transcriptional differences, and potential surface markers specific to adenomyosis. The activity of functional pathways relevant to the candidate genes will be ascertained by immunostaining in full thickness uterine wall biopsies (n=10), and Hyperion IMC (n=3). A 3D reconstruction of adenomyosis will determine its microarchitecture and surrounding structures, using light sheet fluorescence microscopy and digital scanning of consecutive H&E stained endometrial biopsy sections from women with adenomyosis. Finally, a novel in-vitro 3D culture model of adenomyosis will be produced, for pre-clinical drug testing, using primary epithelial organoid cultures from women with adenomyosis (n=10), seeded into a collagen hydrogel containing endometrial stromal cells, and co-culturing these with a primary myometrial cells. The outcomes will inform on the key transcriptomic and phenotypic signature of cells within adenomyotic lesions, which could be targeted with novel therapeutic approaches such as nanotechnology, and can be tested on the 3D in-vitro cell culture model in the future.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Pre-conception health and contraception among migrant women in the UK: a mixed methods study
Funder: Medical Research Council

Abstract: My overarching aim is to develop an intervention to improve pre-conception health and access to preferred contraception among migrant women in the UK. Specifically, my objectives are to: 1. Explore outcomes and health indicators for pre-conception health and contraception among migrant women of reproductive age compared to UK-born women 2. Assess opportunities, needs and barriers to contraception and pre-conception health among migrant women 3. Develop an intervention to improve pre-conception health and contraceptive access among migrant women, and undertake initial piloting Methods A Community Advisory Group (CAG) has been formed (and will be expanded) to allow patient and public involvement throughout the research. Stage 1 A retrospective cohort study using Clinical Practice Research Datalink (CPRD) data will establish primary care attendance, health outcomes and behaviours related to contraception and pre-conception care/health among migrant women aged 15-49 registered with a GP. Differences between migrant and UK-born women will be determined to identify particular areas of need. Stage 2 Building on Stage 1 results, focus groups and interviews with migrant women and key stakeholders will explore, in-depth, facilitators and barriers to the use of and access to contraception and pre-conception care for migrant women of reproductive age. Women with higher needs identified from Stage 1 findings and the literature (e.g. refugees, asylum seekers, and undocumented migrants), and those not registered with a GP will be purposively sampled. Triangulation Stage 1 and 2 results will be integrated in a convergence coding matrix, allowing patterns to be identified and meta inferences across the data to be identified. Stage 3 Opportunities for change will be mapped and a list of issues and potential points for intervention prioritised. The top-scoring intervention option will be co-produced with the CAG.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH