NIHRDataInsights/HRCSData huggingface dataset:
Award Title: What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping.
Funder: Wellcome Trust

Abstract: BMI is a simplified measure of body composition/fatness based on your weight adjusted for height and there are clear correlations between BMI and health. However, it is extremely difficult to change BMI in many people and we still do not understand why BMI is a risk factor.   The processes of our bodies leave behind chemical bi-products which can be measured easily and efficiently. They provide a snap-shot of health status and the relationships between these “metabolites” and BMI can help understand the biological implications of being leaner or larger.   Using collections of metabolites measured in very different studies, I will characterise the downstream effects of BMI on a broad range of biological processes. I will then use very large studies of the general population to bring together evidence and generate a list of metabolites which are affected by BMI. Once done, I will use publicly available genetic studies of disease to help ask the really important question; if BMI has an effect on metabolites, then what do these do to disease risk? Where I find metabolites that do alter disease risk, this will inform future work looking closely at those metabolites rather than attempting to change BMI alone.


Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: CARDIOVASCULAR;ORAL AND GASTROINTESTINAL;METABOLIC AND ENDOCRINE;GENERIC HEALTH RELEVANCE;CANCER AND NEOPLASMS
Award Title: What makes us human?
Funder: Wellcome Trust

Abstract: The Human Developmental Biology Initiative (HDBI) will deliver a step-change in fundamental knowledge about human development leading to improved health outcomes in fertility, birth conditions and regenerative medicine. 
 
What makes us human? will enable a culture of engagement and new ways of working, allowing the science to anticipate, include and respond to a broad range of insights and perspectives. Importantly, this includes consideration of embryo and fetal donors, and staff - including the Human Developmental Biology Resource (HDBR) - who make our research possible, those who consider and regulate our work, and people and patients who (stand to) benefit from our progress. 
 
What makes us human? focuses on developing knowledge, skills and confidence of HDBI researchers and Public Engagement (PE) practitioners through an ongoing programme of training and support. It develops a significant long-term relationship with a multi-stakeholder Insights Group to inform and improve our research, engagement and communications. Built in is provision for responsive dialogue, to be identified by horizon scanning the emerging needs of our research, or changes in the healthcare policy or practice landscape. What makes us human? will raise awareness of and trust in HDB research with a range of public audiences across the UK.


Research Activity Codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health Categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH
Award Title: What’s at stake in the fake? Indian pharmaceuticals, African markets and global health
Funder: Wellcome Trust

Abstract: For the past several decades, global health researchers and policy-makers have raised the alarm about the growing threat that fake pharmaceuticals pose to global health. Often these concerns are framed in terms of particular places and people, for example, fake drugs from India imperil Africans’ health.
 
We subjected these high-profile and oft-repeated claims to scrutiny. This exercise produced some unexpected findings. Across scientific, policy and popular literature, we found substantial misalignments between (1) the strength of claims about fakes alongside (2) the relative weakness of these claims’ evidence. Scientific literature in particular raised questions about apparent certainties, such as: What, exactly, are fake drugs? Are fake drugs necessarily dangerous? Where do they come from?
 
When the global supply of life-saving medicines is beset by worries about safety, governments and citizens face difficult decisions about how to allocate scarce resources. By asking questions about these worries, we hypothesize that the problem of fake drugs is not solely a pharmacological problem; it is also a social problem. 
 
Two questions guide our project’s historical and ethnographic research
 
 1. What accounts for the rise of fake-talk—the wide-spread and urgently-reiterated set of concerns about the dangers that fake drugs present?
 2. What are the effects of fake-talk?

Lay Abstract: Today, the idea that fake drugs threaten global health has become almost common-sensical. Often, these concerns are voiced in relation to how, for example, Africans’ already poor health is further imperilled by fake Indian drugs. Yet when we looked closely at the scientific literature backing up these claims, we found that they were based on unexpectedly weak evidence. This project responds to this puzzle by critically re-examining our collective common-sense about fake drugs and global health. Initial research suggests that, addition to the world of pharmacology, worries about fake drugs may be based in social worlds. When the world’s supply of live-saving drugs is beset by worries about safety, governments and citizens face difficult decisions about how to allocate scarce resources. Our project’s historical and ethnographic enquiries seek to understand the emergence and circulation of worries about fake drugs for global health, as well as to understand these worries’ effects.

Research Activity Codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: Why do some children find language hard to learn? A crosslinguistic comparison of learning processes
Funder: The Academy of Medical Sciences

Abstract: The goal of the study is to pinpoint the underlying cognitive deficit in children who have difficulties learning their native language. Language impairment (LI) in children has been much studied in English, where difficulties particularly affect learning of grammar. I propose a cross-linguistic investigation, comparing LI in English and Tamil. English-speaking children with LI are poor at procedural learning, even when no language is involved. This is evident in weak sensitivity to statistical patterns in a sequential input. Very little is known about LI in Tamil, an agglutinative language where word order is relatively unimportant. I will study procedural and declarative learning in LI children, predicting that the pattern of deficits will relate to the language being learned. I will use a new method to test learning of language-like transitions. The project will also give deliverable products such as language assessment tools in Tamil, and a child-friendly procedural memory task.


Research Activity Codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health Categories: MENTAL HEALTH
Award Title: Work productivity effects of HIV prevention and treatment interventions on populations from endemic settings
Funder: Medical Research Council

Abstract: HIV is a threat to sustainable development and top of the global health research agenda. My research will focus on South Africa which has the largest HIV epidemic in the world and where HIV accounted for about 50% of all life years lost due to illness in 2010. As a major contributor to the burden of disease and for being concentrated in the working age population, HIV comes at large socio-economic cost. Understanding work productivity effects of HIV prevention and treatment interventions (HIVPTI) is thus important for policy makers in their decision to allocate scarce resources most effectively. The impact of HIVPTI on HIV and work productivity can work along several pathways: Healthier individuals are more effective in producing and delivering goods and services both in households and at the workplace. This has social and economic returns, in the form of monetary and wider societal value added. Moreover, as health can be considered an investment good, the prospect of prolonged life lived in better health leads to higher monetary returns of investments into education, hence incentivising individuals to invest in human capital with positive social and economic returns in the long-term. However, the exact consequences of HIVPTI on work productivity and long-term economic development are unknown. Existing evidence on Anti-Retroviral Therapy (ART) effects on work productivity is promising and shows positive correlations of ARTs with economic activities however limited to small-scale observations of unrepresentative sub-population groups. These findings cannot answer the essential questions of productivity effects in the long-term considering HIV-dynamics. Neither provide these studies any basis for generalising findings to the wider public which is the important piece of information required by policy makers deciding on allocating scarce resources in health. My research project will address these gaps in the literature.


Research Activity Codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health Categories: INFECTION
Award Title: YATHU YATHU ("For us by us"): A Cluster Randomised Trial of community-based SRH and HIV services for adolescents and young people in Zambia
Funder: Medical Research Council

Abstract: Yathu Yathu ("For us by us") is a two-arm cluster-randomised trial that will evaluate community-based, peer-led sexual and reproductive health services (SRH), including HIV prevention and treatment for adolescents and young people (AYP), in 2 urban communities in Lusaka, Zambia. SRH services will be established in community spaces in collaboration with adolescent community advisory boards who will advise on the location, content and running of the services. Services offered will include contraception, condoms, HIV testing, STI screening and treatment, VMMC information and referral, ART support groups (face-to-face and via mobile phone), PEP/PrEP services and support groups (by mobile phone), menstrual hygiene products as well as information and support on a range of other subjects requested by young people. The 2 communities are divided into 20 clusters that will be randomized to intervention or control arms. Each intervention cluster will have one community centre with services accessed either at the centre or the health facility. In the control clusters, services can be accessed at the health facility as per the national standard of care. The primary outcomes will be knowledge of HIV status, measured via a cross-sectional survey, and an indicator of coverage measured using an electronic prevention points "Yathu card" provided to all AYP, aged 15-24 years, living in the study communities. Secondary outcomes will include uptake and adherence of specific services such as ART, PreP, or modern contraceptives. In addition economic and qualitative enquiry will provide data on the costs and inputs required to establish the services, barriers and enablers to the use of the services and the experience of AYP in both control and intervention arms.  The study findings will help inform policy-makers on how to best provide SRH services for AYP.


Research Activity Codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health Categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Award Title: mRNA cap regulation of gene expression, cell function and fate
Funder: Wellcome Trust

Abstract: Human life utilises hundreds of cell types with massive diversity in function defined largely by which proteins they express. We will determine how regulation of the mRNA cap modification coordinates the gene expression required in different cell types. The cap protects mRNA from degradation and recruits processing and translation factors. The enzymes which catalyse cap formation were perceived as acting on all genes, in every cell. Our research reveals that the capping enzyme complexes are differentially expressed in different tissues and have gene-specific impacts. During cell differentiation, we demonstrate that changes in capping enzyme complexes result in coregulation of gene families, which we hypothesise co-ordinates the gene regulation required for new cell identities to emerge.Key goals are to determine:  1. mechanisms governing capping enzyme gene-specificity  2. how co-factors influence capping enzyme functionality 3. the impact of mRNA cap regulation in differentiation In pluripotent cells, the components of mRNA capping enzyme complexes will be characterised and their impact on enzyme kinetics, cap formation and sequence-specific RNA selection determined. During differentiation, how mRNA capping enzyme regulation impacts on enzyme function and gene expression will be investigated. This project will determine the dynamic impact of mRNA capping enzyme regulation. Keywords: gene regulation; mRNA; cell function

Lay Abstract: Humans contain hundreds of different cell types, whose function depends on the proteins they contain. Each human cell contains over 25000 genes which are the instructions for making proteins. We want to understand how cells control which proteins are made and how this process changes in different types of cell.We discovered that a structure called the mRNA cap controls which proteins are selected for production in the cell.  When cells develop, we found that how the mRNA cap is made changes and this alters which proteins are made. We aim to discover how the mRNA cap controls which proteins are made in a cell. When cells develop, we will investigate how changes in the cap influence which proteins are made and how this helps produce new types of cell.This project will indicate potential ways that we could influence which proteins are made in cells in medical therapies.

Research Activity Codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health Categories: GENERIC HEALTH RELEVANCE
Award Title: novel labelling and tracking strategies to understand mesenchymal stem/stromal cell populations relevant to musculoskeletal regenerative therapy
Funder: Wellcome Trust

Abstract: Bone marrow-derived MSCs can exert strong therapeutic effects in the musculoskeletal system and cell therapies have developed to regenerate and repair cartilage defects. However, our understanding of the biology of this heterogeneous group of cells is incomplete and there are still many hurdles to their wide application in the clinic.
 
We will use a combination of labelling techniques and novel cell markers developed in Cambridge to track labelled cells in vivo to determine their survival, engraftment and distribution. The biology of unlabelled and labelled MSCs will be studied in vitro to confirm that the labelling does not affect the cells’ function. Labelled cells will be injected into a mouse knee (after creation of a cartilage defect) and repeated imaging will be used to track the distribution of these cells to study their biology in greater detail.
 
With the current focus on moving cell therapies to the clinic, in vivo tracking of these cells is critical in assessing their homing and proliferative potential over time. The novel genetic labelling strategies used will provide important information regarding graft behaviour in small animal models, offering both fast readouts of longitudinal cell survival and low costs per imaging study.


Research Activity Codes: 5.2 CELLULAR AND GENE THERAPIES
Health Categories: MUSCULOSKELETAL