NIHRDataInsights/HRCSData huggingface dataset:
Title: Managing Covid-19 in India’s Cities: reshaping people’s everyday lives in poorer urban neighbourhoods
Funder: The British Academy

Abstract: Covid-19 is transforming lives and livelihoods globally, and is particularly challenging in cities of the Global South. Urban spatial practices – managing social distancing, density and containment – and everyday governance – ensuring policies’ translation into ‘on the ground’ effects – are central to these challenges. Taking a comparative urbanism approach, this study examines how local management of the crisis is reshaping people’s spatial practices in poorer urban neighbourhoods. Based in three Indian cities with contrasting experiences of the pandemic, Ahmedabad (Gujarat), Chennai (Tamil Nadu) and Trivandrum (Kerala), it draws on an established network of researchers with extensive experience of each city to generate context-rich understandings. It investigates the experiences of front-line staff, poorer residents and urban managers, combining this with secondary data to provide detailed insights into the challenges cities face, and to explore sustainable, socially-inclusive responses to Covid-19 that will be rapidly translated to academic and policy audiences.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Psychological “vaccines” against online misinformation, vaccine hesitancy and extremist recruitment strategies
Funder: The British Academy

Abstract: Online misinformation is a pervasive global threat, according to the World Economic Forum. As a British Academy Postdoctoral Fellow, I will develop a theory of psychological resistance to unwanted persuasion in the digital era. In service of this, I will conduct four separate research projects related to inoculation theory and online misinformation, each of which will advance our knowledge how psychological resistance to persuasion works across different cultures, to what extent "herd immunity" against online misinformation is possible, and the role that threat, memory, motivation and perspective-taking play in inoculation interventions. In addition, this project will yield several practical, scalable real-world interventions. The first three projects focus on issue domains where the proliferation of manipulative content poses a significant threat to society: vaccine hesitancy, the novel coronavirus (SARS-CoV-2), and online recruitment by extremist organisations. The fourth domain focuses on the development of psychological “herd immunity” against misinformation through agent-based modelling.


Research activity codes: 3.4 VACCINES;7.1 INDIVIDUAL CARE NEEDS
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: For better or worse? An immersive diary study of the effects of return to work policies on disabled employees
Funder: The British Academy

Abstract: One in five employees in the UK (19% of the working age population, or 7.9 million people 16-64) reported a disability in 2019. Although 53.2% or 4.2 million of disabled people were employed, an increase of 2% or 354,000 from the prior year, the unemployment rate is 2.5 times that of non-disabled people, as employers have historically resisted the range of accommodations instantly implemented across a wide range of occupations and workplaces during the home quarantine stage of the COVID19 pandemic. Most of these social distancing policies will be progressively released through the staged return to work with interruptions and updates projected until late 2021. Disability organizations warn against “a return to ableism” instead, as work accommodations originally exclusively extended to disabled people became a burden to undo for those without disability. This 18-months diary study follows 20 UK-based disabled employees/free-lancers who repeatedly renegotiate vulnerabilities and accommodations.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Adherence to COVID-19 public health practices in adolescence: The role of morality, group dynamics and personal choice
Funder: The British Academy

Abstract: Adolescents face a reduced risk of severe symptoms or death from the novel coronavirus, yet there is some evidence that youth can transmit the virus at the same rate as adults. Until an evidence-based consensus is reached regarding transmission, it will be important to promote adherence to public health practices (e.g. social distancing, hand washing) among adolescents. Crucially, there is a need for research exploring how adolescents themselves reason about these issues. The proposed project will examine adolescents’ reasoning about public health practices and whether this is related to behavioural intentions to engage with these practices. Second, the project will examine how misinformation can impact adolescents’ reasoning and public health behavioural intentions. Together this evidence will inform the communication of COVID-19 related information in order to promote youth engagement with public health practices and challenge the potential consequences of misinformation.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Fighting fake news: online disinformation in COVID times
Funder: The British Academy

Abstract: Fake news amplifies existential threats posed to societies recently exemplified by the antivaxx movements. Using social media analysis, this research identifies discourses adopted by antivaxx campaigns and the most effective counter-campaigns to fight online harm and reduce vaccine hesitancy in Italy, France and Ireland. We will analyse the discursive strategies and the cultural, social, legal and economic factors that might influence the diffusion of misinformation on COVID 19. Through our expertise in emotional socio-symbolic strategies we will focus on the role of emotions, not only disseminating fake news but in fighting fake news. We will translate the findings into strategies for policymakers and NGOs to more effectively overcome reduce vaccine hesitancy. The findings will also inform the wider regulatory space in the EU, Member States and the UK, where legislative and policy efforts are being made to improve online safety and the accountability of online platforms.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Community-based Health
Funder: Royal Academy of Engineering

Abstract: This research is developing new technologies for low-cost medical diagnostics by combining the accuracy and sensitivity of DNA and RNA testing technologies (such as the ‘PCR’ test) with the convenience of lateral flow technologies. This will result in highly sensitive tests that can be widely used at home or in community settings and will contribute to greater resilience not only to new outbreaks of infectious diseases but also to the many infectious diseases that are currently endemic in many parts of the world, such as schistosomiasis and malaria.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: ShareAction: Long-term investors in people’s health transitional award
Funder: The Health Foundation

Abstract: Good health is the bedrock for a thriving society. Our health is determined by the conditions in which we are born, work, live and age. The Covid-19 pandemic has underscored pre-existing societal challenges such as inequalities and high levels of chronic ill-health. It led to a labour market exodus across the OECD and highlighted the vital role good health plays in driving economic prosperity. Of the roughly half a million Britons aged 15-64 still missing from the workforce since the pandemic begun, two in three cite long-term illness as their reason for not holding or seeking a job. In the US, poor health costs businesses an average of $3,900 per employee per year through absences and lost productivity. Poor diets are a key driver of ill-health, linked to 1 in 5 deaths globally, other factors like smoking, alcohol consumption and air quality are all important risk factors, too. Poor health is exposing investors and many of the businesses they’re invested in to elevated and preventable financial risk. That’s why we’re establishing the Long-term Investors in People’s Health (LIPH) initiative. A global initiative that will support investors to give greater priority to health within their work.

Lay abstract: Good health is the bedrock for a thriving society. Our health is determined by the conditions in which we are born, work, live and age. The Covid-19 pandemic has underscored pre-existing societal challenges such as inequalities and high levels of chronic ill-health. It led to a labour market exodus across the OECD and highlighted the vital role good health plays in driving economic prosperity. Of the roughly half a million Britons aged 15-64 still missing from the workforce since the pandemic begun, two in three cite long-term illness as their reason for not holding or seeking a job. In the US, poor health costs businesses an average of $3,900 per employee per year through absences and lost productivity. Poor diets are a key driver of ill-health, linked to 1 in 5 deaths globally, other factors like smoking, alcohol consumption and air quality are all important risk factors, too. Poor health is exposing investors and many of the businesses they’re invested in to elevated and preventable financial risk. That’s why we’re establishing the Long-term Investors in People’s Health (LIPH) initiative. A global initiative that will support investors to give greater priority to health within their work.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Adult social care and safeguarding during COVID-19: a large-scale mixed methods study
Funder: The Health Foundation

Abstract: While there has been a drive to ensure health care providers are adequately equipped to deal with the effects of COVID-19, there has been limited research into the pandemic in the context of adult social care or adult safeguarding. A survey by the British Association of Social Workers found that many local authorities were underprepared and struggled to meet their legal obligations during the first wave of the pandemic. Moreover, the Coronavirus Act 2020 included scope for widespread suspension of key duties under adult social care legislation, which has resulted in concerns that adults who require care and support were not having their needs met. This project is the first in-depth research into the relationship between COVID-19 and adult social care and safeguarding. It will focus on services across local authorities and Safeguarding Adults Boards in England and Wales. Research methods will include a literature review, Freedom of Information requests, surveys and stakeholder interviews. The research will provide a better understanding of what changes are happening to the legal obligations and practice of adult social care and adult safeguarding as a result of COVID-19. The findings will also be used as evidence as to how best to support the delivery of social care, social work and safeguarding in the future, for the duration of the pandemic and beyond. The results will be disseminated through both social care and academic channels, and will involve a white paper, a webinar, practitioner-orientated blogs, briefings, reports and two peer-reviewed journal papers.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Long-term investors in people’s health programme (LIPH)
Funder: The Health Foundation

Abstract: Companies play an important role in shaping the social, commercial, and physical environments that in turn influence health – through the goods and services they sell, the quality of jobs they provide, and how they shape local communities and environments. Where companies invest their capital also has the potential to influence health. Yet most investors are overlooking health as an ESG (environmental, social and governance) issue, partly because of the lack of good quality and comprehensive data. The LIPH programme will give investors the tools to improve health outcomes for workers, consumers, and communities, by sharing best practice and creating opportunities to collaborate on corporate engagement. Investors are asked to commit to embed health into their policies and practices and use their influence to accelerate impact throughout the investment sector.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Reshaping secondary care consultations after COVID-19: the role of asynchronous consultation methods
Funder: The Health Foundation

Abstract: COVID-19 has changed many aspects of health care, including how consultations are managed. Remote consultation methods (for example phone or video) were gradually being introduced before COVID-19, but in March 2020 most face-to-face contacts were replaced by remote consultations. Most research around remote consultations has focused on ‘synchronous’ forms, where patients and clinicians talk online or by phone in real time. There is less research on ‘asynchronous’ consultations, where patients and professionals are not available at the same time. Examples of this include emails and text messages, but more sophisticated systems have been developed which are more like the flow of information in face-to-face consultations. NHS Grampian in Scotland has been piloting asynchronous consultations using a platform developed by Storm-ID. Patients have a five-day ‘appointment’ to complete questions online and upload photos. The doctor then looks at these and may request further information, make a diagnosis or treatment plan, invite the person for a phone or face-to-face appointment, or discharge them. As part of its COVID-19 recovery plan, NHS Grampian will roll out an asynchronous platform across more specialties. This research project will explore the roll out of this system at scale. Using telephone/online staff and patient interviews, a patient survey and focus groups, and analysis of consultation and resource use data held by NHS Grampian, the project team will analyse whether it is acceptable to patients and staff, how it changes the nature of the consultation, who is advantaged/disadvantaged by the system, and what can be learned for future roll out in the NHS.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: The signaling of phagosome biogenesis and its subversion by intracellular pathogens.
Funder: Medical Research Council

Abstract: Aims 1. Characterisation of protein phosphorylation events modulating phagosome biogenesis. 2. Characterisation of host-targets of bacterial pathogen factors modulating phagosome biogenesis and other immune functions in macrophages. Plan of Investigation Phagosomes are organelles formed by the uptake of particles or pathogens by specialised immune cells such as macrophages. Phagosomes mature by a number of fusion events with endosomes and the lysosome, forming a phagolysosome in which these pathogens are killed and degraded. Antigens of the microbes are then presented via the MHC class I and II pathways, thus linking innate and adaptive immunity. Unfortunately, many pathogens including Mycobacterium tuberculosis, the causative agent of tuberculosis, are able to subvert phagosome maturation/biogenesis by injection of pathogenic factors into the phagosome, enabling them to survive. Very little is known about the signaling events leading to phagosome biogenesis. We will analyse the proteome and phosphoproteome of phagosomes by large-scale mass spectrometry approaches. For this, we will generate high purity phagosome fractions from mouse macrophage cell cultures by the use of opsonised polystyrene beads and subsequent sucrose gradient ultra centrifugation. By analysing phagosomes internalised upon different routes of entry and different maturation times, we will generate a large dataset that will help us understand the signaling events regulating phagosome function over the whole time-scale important for phagosome function. In addition, we will analyse the phagosome proteome and phosphoproteome upon challenge with secreted bacterial effectors such as the mycobacterial protein kinase G which has been shown to be involved in blocking phagosome maturation, enabling Mycobacterium tuberculosis to survive within the phagosome of macrophages. As phagocytosis is a key mechanism in innate and adaptive immunity, identification of the mechanisms of phagosome biogenesis will be of importance for our understanding of infectious diseases and vaccine design. Moreover, insights of how pathogens subvert phagosome maturation will enable us to target bacterial pathogen factors for drug design.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Developmental Clinical Studies - Depletion of serum amyloid P component to enhance the immune response to DNA vaccination
Funder: Medical Research Council

Abstract: Parenteral injection of naked DNA encoding immunogenic epitopes is a highly desirable approach to vaccination but, for reasons which have not hitherto been understood, it is not efficacious in some species, including humans. Serum amyloid P component (SAP) is the single normal human plasma protein which binds avidly to DNA under physiological conditions. We have lately discovered that, among species tested so far, there is complete concordance between the efficacy of DNA vaccination and the absence of circulating SAP which binds strongly to DNA. Mice respond well to DNA vaccination and their SAP binds DNA very weakly. It has lately been reported that human SAP potently blocks murine immune responses to DNA vaccination and that this inhibition is completely abrogated by CPHPC, the SAP depleting drug developed by Pepys. We now propose to conduct the first human clinical trial of DNA vaccination in subjects undergoing SAP depletion by CPHPC. Medicinal CPHPC and a suitable GMP DNA vaccine against HIV-1 are available, together with extensive expertise in conduct of HIV vaccine trials and monitoring of SAP and CPHPC. Forty healthy adult male volunteers will receive three priming doses of DNA vaccine, followed by a protein antigen boost. Half the subjects will be randomly allocated to receive a CPHPC infusion to provide maximal SAP depletion at the time of each DNA injection; controls will receive saline alone. Comprehensive assessment of the T cell immune response to each priming dose and to boosting, including viral suppression assays, will establish whether the immune response is significantly enhanced by SAP depletion and achieves a clinically useful level. A positive result will open the way in humans to use of prophylactic and therapeutic DNA vaccination against major infections including HIV, malaria and tuberculosis, and also cancer, with enormous potential health and economic benefits.


Research activity codes: 6.1 PHARMACEUTICALS;3.4 VACCINES
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: Integrating statistical genetics with nonlinear fixed effect pharmacokinetic models to advance high-throughput personalized drug therapy
Funder: Medical Research Council

Abstract: Pharmacogenetics in pharmacokinetic (PGPK) studies explore the role of genetics in drug response and hold much promise to provide advances leading to improved patient care, as well as economic benefits to the pharmaceutical industry and to public healthcare providers. In this project we seek to integrate state-of-art statistical genetics with sophisticated statistical modelling. Most PGPK studies focus on a few single nucleotide polymorphisms (SNPs) that are suspected of being implicated in the drug disposition or effect. We will identify and develop optimal statistical approaches to incorporate a larger set of SNPs into PGPK studies using nonlinear mixed effects (NLME) models. These models allow quantification of parameters influencing the physiological processes, including characterisation of between-subject variability and may take advantage of relatively sparse designs, where many subjects contribute only a limited amount of information. In work done to date, the multiple SNP penalised regression algorithm, HLASSO (Hoggart et al. 2008), proved more powerful than the commonly used stepwise approach (Lehr et al. 2010) and much faster. Consequently, methods to enrich the genetic information appear feasible in conjunction with an NLME approach. First we plan to evaluate other penalised regression algorithms in conjunction with NLME models based on realistic simulations. Then, we will compare the multiple imputations approach coupled with multiple SNP analysis to the haplotype-based alternative to infer on ungenotyped variants in PGPK studies using NLME models (aim 1). In a second stage, we will extend the NLME estimation algorithm to encompass penalized regression on the genetic effect coefficients and evaluate its implementation (aim 2). Finally these developements will be applied to the analysis of a PGPK study on nevirapine conducted in Cambodian HIV patients and PKGK studies from the Servier pharmaceutical company (aim 3).


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE;INFECTION
Title: The myosin VI interactome: the role of motor cargo/adaptor complexes and ubiquitin-binding during selective autophagy
Funder: Medical Research Council

Abstract: This research project aims to establish the molecular role of the actin-based motor protein myosin VI in autophagy. In this pathway cytosolic protein aggregates and pathogens are sequestered in autophagosome, which can fuse and deliver its contents to the lysosome for degradation. Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's, Huntington's and Parkinson's disease are characterized by the accumulation of intracellular ubiquitin-containing protein aggregates and defects in autophagy can cause neurodegeneration. Interestingly, we have identified three myosin VI interacting proteins, NDP52, optineurin and T6BP that can function as autophagy receptors linking ubiquitinated cargo to be degraded to the autophagy machinery. In this process NDP52 and optineurin have been shown to be essential for clearance of pathogens from the cytosol of eukaryotic cells by autophagy and mutations in optineurin have been linked to the familial form of the motor neuron disease (ALS), where optineurin has been identified on SOD-1 and TDP-43 protein aggregates. Intriguingly, myosin VI has also been linked to neurodegeneration, since it was shown to associate with neurofibrillary tau tangles in Alzheimer's disease patients as well as in a transgenic mutant tau mouse. Myosin VI is a unique reverse direction myosin motor protein that functions in a wide variety of intracellular processes including cargo sorting and vesicle transport in the endocytic and secretory pathways. In this proposal we will build upon our recently published work on the cellular functions of myosin VI and use our tools together with reagents and knowledge to establish the molecular role of this motor in autophagy for the clearance of protein aggregates and bacterial invaders. We will determine how myosin VI is recruited to autophagosomes and whether dysfunction of this motor affects membrane delivery required for autophagosome biogenesis, maturation or fusion with the lysosome.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE;INFECTION