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Strategies for the control and elimination of blinding trachoma. 01 Nov 2005

Trachoma, caused by ocular Chlamydia trachomatis infection, is the commonest infectious cause of blindness. We have shown that a single round of mass treatment with azithromycin can eliminate the infection from endemic populations for up to two years. The studies proposed here will enable this drug to be used to maximum effect. We will Determine the sensitivity and specificity of a new rapid point-of-care (POC) diagnostic test for ocular C. trachomatis infection in communities with high, medium and low prevalence of trachoma in three countries, before and after mass treatment. Use the above data, datasets from our current Wellcome Trust-Burroughs Wellcome Fund grand, to develop optimal sampling strategies to assess the need for community-based mass treatment depending on the prevalence of clinical signs of trachoma or of ocular C. trachomatis infection, determined by the POC test. Use this data to model the impact and cost-effectiveness of strategies in which a POC test is used to decide whether a community should be treated, and to compare this with the cost-effectiveness of the current strategy, based on the prevalence of clinical signs of trachoma.

Assessment of Exeter Partnership NHS Trust records. 20 Sep 2006

The Devon Partnership NHS Trust, providing mental health and learning disability services for Devon has decided to discard a substantial number of individual patient records, together with at least two different card indices. These materials appear to date mainly 1930s - 1960s and are to be destroyed unless archived. They represent an important resource for researchers and for the engagement of scientific and historical scholarship with the wider public. The Devon Archivist has accepted the need to house these materials on a temporary basis until an effective means of sampling and retention can be found. The rationale for retaining these materials and developing a clear model for sampling what is a collection of some ten thousand patient files can be simply stated. Earlier deposits of health records, in particular those relating to mental health, have provided a foundation for major research initiatives at the Centre, including detailed studies of mental services in south west England before 1939. Relatively few collections of patient records for the post-1918 period have survived, though they complement studies of the nineteenth century which have drawn largely on such materials. The present proposal is for a brief (approximately 3 months) investigation of the medical records to assess their scope and organisation, and to identify an appropriate strategy for future sampling. The proposal envisages funding for one member of staff (a Research Assistant) under the direction of Dr Jo Melling (the applicant), in collaboration with the Devon Archivist, but housed in the Devon Record Office. John Draisey (Devon County Archivist) has agreed to the Research Assistant using office space, telephone facilities and associated resources at the Devon Record Office. Management will be arranged by monthly meetings, with reports prepared by the Research Assistant.

Amount: £8,823
Funder: The Wellcome Trust
Recipient: University of Exeter

The performance of medicine : researching the historical writings on the ritual of tarantism. 13 Jul 2008

The project for which this grant is being sought, is for proposed archival research into specific aspects of medical history relating to the phenomenon of tarantism. The grant will allow for detailed examination of documents and sources contained within two libraries, the Wellcome Trust Library, London, and the Bodleian Library, Oxford, both of which hold significant material relating to the historical study of the medical writings concerning tarantism, which date from the 15th Century through to the present. The key goals of this archival research are that it will contribute toward the writing of a monograph, Ritual, Rapture and Remorse: the dance of the spider in Salento, under contract with Peter Lang, which is a study of the history of tarantism through different disciplinary perspectives, and includes discussion of the extensive amount of documentation within the field of the history of medicine. This will make an important contribution to dissemination of these writings, each of which demonstrates the shifts in approaches to the body, medicine and scientific and philosophical paradigms, most particularly in Renaissance and Early Modern Italy, but also moving through to the developments in psychiatric medicine during the 20th Century.

Amount: £1,297
Funder: The Wellcome Trust
Recipient: University of Exeter

Enabling Public Health Foundation of India's Network of Indian Institutes of Public Health. 14 Apr 2008

Broadly, the desired outcomes to which this strategic award will contribute include: - Eight IIPHs created over the course of the next 8 years with each demonstrating active faculty, teaching and research programmes, an effective public health advocacy and health policy role, relationships to enable research across priority areas, including state and central government, multi- and bilateral agencies, academic institutions and civil society agencies - A multidisciplinary cadre of public health professionals and practitioners developed and working within IIPHs. Over the 5 years of this proposal, a majority of the faculty in each of the first three IIPHs that are now planned to open between July 2008 and July 2009, will be trained and strengthened. It is expected that each IIPH will start with a complement of 20 faculty, growing to about 70 faculty at full strength - IIPHs with collaborative research programmes, Masters courses underway, a range of other training courses, formal lin kages with local government, health services and NGOs, scientific output, and a sustainable and growing number of high quality students registered for training

Amount: £2,297,400
Funder: The Wellcome Trust
Recipient: London School of Hygiene & Tropical M...

Constructing the patient consumer: patient groups and health consumerism, 1960-1991. 28 Mar 2008

This project examines the activities of three different types of organisation that claimed to speak and act for the patient consumer from the 1960s until the creation of the Patient's/Citizen's Charter in 1991. The project will consider: the work carried out by dedicated patient groups, the focus here will be on the Patients' Association and the National Association for the Welfare of Children in Hospital; the involvement of general consumer groups in health issues, attention here will be directed towards the actions of the Consumers' Association and the National Consumer Council; the efforts of quasi-statutory bodies tasked with representing patients in the form of a selection of the Community Health Councils. In focusing on these examples this project aims not to be a study of separate organisations, but will instead use these to address broader questions about the construction of the patient consumer 1960-1991. The project thus has 4 thematic aims: 1. To unpick the changing meaning of the 'patient consumer' 2. To assess the changing demands of the 'patient consumer' 3. To understand the nature of the relationship between patient groups and health professionals 4. To understand the nature of the relationship between patient groups and the state

A socioeconomic evaluation ofcommunity based health insurance in Anambra stateNigeria 31 Aug 2007

How to ensure that the poor and vulnerable groups are protected against ill health has remained a problem especially in the developing countries. In many cases, the poor are exposed to difficult health conditions and often stand no chance of survival because they lack the financial power to take care of themselves. It is therefore necessary to evaluate the risk protection options that are available so as to know how the poor are considered. We need to know if there are differentials in incentives for health care suppliers to protect the poor. We shall also investigate the willingness and ability of the CBHI programme managers to monitor, regulate and ensure that healthcare providers comply with rules and regulations of the programme to ensure financial risk protection of the people. The method of the research will include qualitative and quantitative data collection and the analysis will be done using SPSS, STATA and EpiInfo for quantitative data while qualitative data will be analysed using Text-base-beta software packages. It is expected that we shall be able to come up with recommendations on how best to improve community based health insurance in the country.

MA in Medical History. 31 Aug 2007

The mind and its inexorable relationship to the early modern body caught my imagination specifically, and my dissertation was influenced as such. 'Lovesickness' became the core focus of my thesis. Not only did I discover a historiographical lacunae in this field of medical history, but, surprisingly, an incredible amount of source material relating to this disease in both popular and medical tracts of the seventeenth century. Through my research I began to establish the hypothesis that it was this period that witnessed the articulation of the female body as that primarily affected by this disease. Discovering that it was associated with sexual appetite and mental instability, I concluded that lovesickness was grounded deliberately in the fundamental characteristics of the female anatomy in order to posit her gender as sexually and mentally volatile. As such, a diagnosis of 'lovesick' served perfectly to validate a young women's exclusion from the public and intellectual domains, thus supporting the common early modern paradigm of female subjection. Yet while this may have implied the historical fiction of lovesickness, I believe that my analysis also elucidated a genuine disease that may have inspired the invention. Indeed diary entries, newspaper articles, and the predominance of the lovesick maid in popular ballads inferred that real women experienced the tumults of love both physiologically and psychologically. If permitted what I would like to investigate is the disparity in representation between the male and female versions of the disease. Was male lovesickness as much of a cultural phenomenon as the female version, or was it simply a literary relic deriving from the Middle Ages (when the term Amor Heroes implied the masculinity of the disease, as attested by the historian Mary Wack)? Did male lovesickness reside in a different area of the body to that of female lovesickness, and did love enter the body through the same channels? Was the male less, and the female more susceptible to the disease due to their humoral characteristics? Was female lovesickness more innately sexual that male? In medical accounts of authors such as Jacques Ferrand, he seats the disease potentially in the testicles, yet does not link this explicitly to sexual appetite, whilst with the seating of the disease in the womb, he does. Was the male sufferer, therefore, more prone to the melancholic rather than the erotic stage of lovesickness? And as in female accounts of the disease, was the male sufferer always young? And finally, I would like to investigate whether genuine cases of lovesickness inspired the fictive accounts of the male malady, as they did the female. Thus there are an incredible number of avenues to research in this field, if indeed I am granted the opportunity to do so.

Amount: £20,153
Funder: The Wellcome Trust
Recipient: University of Exeter

MSc in Public Health. 31 Aug 2007

Lay health workers (LHWs) are increasingly being trained to look after primary health care and preventative programmes, because of local and political motivation to address health development needs. LHW programmes are seen as encompassing all of the Alma-Ata principles. Many terms have been used to describe LHW (e.g. community or village health workers). The definition of a LHW given in a recent Cochrane review is any health worker who performed functions related to health care delivery who was trained in some way in the context of the intervention, but had received no formal professional or paraprofessional certificate or tertiary education degree. This project focuses on the development of LHW programmes in South Africa, where the growth of these programmes coincided with the apartheid era and consisted mainly of local initiatives rather than a nationally developed plan. In the context of segregationist policies of the apartheid state (1948-1994), the health of black people was systematically undermined. The implementation of the Bantustan system where the Blacks in South Africa were forcibly segregated to the 'independent homelands', lead to poverty, repressive conditions, and a dearth of financial or political commitment to their health services. The department of health also became part of the oppressive apparatus of the State .

A genetic component to the INDEYE study of cataract and age-related macular degeneration in India . 02 May 2007

India accounts for a quarter of global blindness. The high rates and unique patterns of type of cataract in India are likely to be due to a combination of environmental and genetic factors. There has been exciting recent progress in genetic risk factors for age-related macular degeneration (AMD), but the role of various candidate genes in populations of non-European origin remain unresolved. INDEYE is a Wellcome Trust funded study of environmental risk factors for eye disease among 6000 older (60+) people in two centres in the north and south of India. We propose a genetic extension to the INDEYE study with four goals. Firstly, an additional sample of 3000 people aged between 40 and 59 years will be recruited. Secondly, DNA will be extracted for all 9000 participants. Thirdly, we will increase the sample size of AMD cases by recruiting an additional 500 cases to increase study power. Fourthly genetic association studies for both cataract and age related macular degeneration will be undertaken. The project will create a unique resource of several thousand genetic samples from a population based study in India with high quality digital lens and retinal photographs and full information on environmental risk factors.

Wellcome Trust Clinical PhD Programme in International Health at the LSHTM: 'The roles of non-specialist health workers in mental health care provision in developing countries'. 31 Aug 2009

With the significant burden of mental illness in developing countries, the large treatment gap due principally to scarcity of skilled mental health personnel and inequities in their distribution, non-specialist health workers (professionals and non-professionals) (NSHW) are important for task-shifting within mental health care. Growing evidence for NSHWs? use in mental health care highlights the need to systematically examine their roles. India has pioneered decentralised mental health services since the 1970s but so far has had limited success in increasing coverage. Describing programmatic achievements and failures and understanding roles of NSHWs within mental health care are essential for informing policy makers and for building recommendations on effective implementation and sustainability of scaling up community mental health services in India and other low income countries (LICs). This project systematically reviews LIC mental health initiatives, which has not been done before. It explores the history and development of NSHWs? roles in mental health care provision in India through oral and written historical primary source analysis, describes NSHWs current roles through ethnographic observation and interviews and uses Delphi and workshop methods with key international and Indian stakeholders to examine the acceptability and feasibility of non-specialists? roles to inform the development of policies in LICs.

Genetic and phenotypic characterisation of emerging virulent Clostridium difficile. 02 Oct 2008

The current epidemic of C. difficile-associated disease has been accompanied predominantly by the emergence of two clonal groups of 027 and A-B+ strains that are associated with increased disease severity. We recently compared genome sequence data from historical non-epidemic and contemporary epidemic 027 and A-B+ strains and identified several genetic regions of difference that could explain the emergence of the epidemic phenotype. In parallel studies, assays have identified significant pheno typic differences between non-epidemic and epidemic 027 strains. In this study we will determine the genetic and phenotypic attributes that could explain the emergence of epidemic strains. This will include the rigorous characterization of epidemic strains and respective mutants using relevant in vitro and in vivo assays. In complementary studies, comparative phylogenomics, MLST analysis and SNP typing will be used to establish an evolutionary framework for C. difficile strains. This analysis wi ll help to (i) determine the distribution of newly found virulence determinants, (ii) trace the origin of 027 and A-B+ strains and (iii) predict the emergence of further epidemic clones. The two lineages of epidemic C. difficile provide a unique opportunity to study the recent emergence of hypervirulent bacteria and improve our general understanding of the evolution of bacterial virulence

Community Engagement and Ethical Practice in Vaccine Research. 18 Feb 2009

KEMRI/CDC is involved in a multi-site phase III infant vaccine study aimed at evaluating the efficacy of an oral Rotavirus vaccine in African and Asian populations. At the KEMRI/CDC field station 1000 participants have been recruited from five rural clinics in Karemo Division in western Kenya. This is the first vaccine trial KEMRI/CDC has conducted, and the first clinical trial in this division. Preparations included community consultations, stakeholder meetings and the establishment of a commu nity advisory board. Vaccine research will continue in Karemo with a Malaria infant vaccine efficacy trial scheduled to start in January 2009 and future Tuberculosis vaccine studies planned. These studies present an important opportunity to observe and document how the field research station engages with the community, and consider how these strategies and activities support ethical practice. Participant observation, which is central to an ethnographic approach, will allow researchers gain insi ghts into the context, while semi-structured interviews and focus groups will provide the opportunity to explore the perspectives of field station staff, community members and representatives, as well as parents of participants. The results will provide a critical analysis of the practice of community engagement, which has been described as a benchmark of ethical research (1).

Rewriting the System of Nature: Linnaeus's Use of Writing Technologies. 13 Nov 2008

Although the cultural turn in the history of science and medicine has considerably raised awareness for the contextual importance of material artefacts and practices, medical and scientific knowledge itself is still largely seen as something which is exemplified by cognitive entities: the concepts, theories, and methodologies that scientists hold and use. This project would start from a different perspective by assuming that any form of socially organized knowledge is essentially written knowled ge, and proceeds through the development, deployment and dissemination of writing technologies. While the project focuses on the corpus of manuscripts and publications of a single scientist, Carl Linnaeus (1707 1778), I conceive it as a pilot project that will serve to develop both a terminology and a methodology that is attentive to the materiality of writing, and will have ramifications for how the history of science and medicine is done in general. In particular, it will bring historiography closer again to the defining mark of modern science and medicine: their reliance on forms of inductive reasoning operating on a social and global scale, and the concurrent emergence of ontological concepts of collective entities like species, disease categories, and human types .

Amount: £119,746
Funder: The Wellcome Trust
Recipient: University of Exeter

Chromosomal recombination and repair in African trypanosomes. 13 Jul 2009

The African trypanosome, Trypanosoma brucei, is an important human and animal pathogen. In T. brucei, antigenic variation is essential for survival in the mammalian host and involves homologous recombination (HR) at subtelomeric loci, leading to the genetic reassortment of variant surface glycoprotein (VSG) genes. The molecular controls and mechanisms underlying this process remain only partially characterised. We recently used inducible expression of a meganuclease to spatially and temporally c ontrol the introduction of a single DNA double-strand-break (DSB) per T. brucei genome. Our studies revealed efficient HR-mediated repair of the DSB at a chromosome-internal locus but little repair at a transcriptionally repressed sub-telomeric locus. End-joining repair was also detected but this was exclusively microhomology-mediated. We now propose to employ the meganuclease system to dissect the pathways and control of DSB repair in T. brucei. We will determine which pathways are enacted by D SBs at different loci and which cell-cycle checkpoints are invoked in these settings. We will monitor the assembly of the repair machinery at the different DSBs and genetically dissect these pathways. The work will reveal the molecular mechanisms that are co-opted for immune evasion in this important pathogen.

The epidemiology, spatial ecology and transmission dynamics of co-infection with plasmodium falciparum and hookworm in East Africa 29 May 2009

The epidemiology of plasmodia-helminth co-infection is poorly understood. This is despite increasing evidence that co-infection may enhance individual susceptibility to clinical malaria and recent advocacy for the logistical and economic benefits of integrated disease control targeting multiple parasites. This proposal details a range of field and modelling studies aimed at understanding the epidemiology, geography and transmission dynamics of co-infection with Plasmodium falciparum and hookworm in East African children. The proposed field studies will provide better descriptions of the patterns of transmission and the risk factors for co-infection in a variety of environmental and socio-economic settings. This information will be used to develop innovative geostatistical models to predict the spatial range of co-infection. Mathematical models will be developed of the dynamics of co-infection within communities in relation to key geographic heterogeneities and augmented with geostatistical models to determine the paediatric population at the risk of co-infection in East Africa. The resulting products will provide decision-makers with better information with which to design integrated disease control strategies in the region. They will also provide a credible academic framework for future work on the individual, population and thus public health consequences of co-infection.

Value in People Award. 21 Oct 2008

Not available

Studies in the pathogenesis and control of blinding trachoma. 05 Dec 2006

Trachoma is the leading infectious cause of blindness. Recurrent Chlamydia trachomatis conjunctival infection from childhood initiates a poorly understood inflammatory scarring response leading to blinding sequelae. Control measures focus on mass antibiotic treatment of chlamydial infection, but it is unknown if this will reduce future scarring and blindness, because conjunctival inflammation often persists after treatment.The aim is to identify the principal immunological and fibrogenic responses associated with progression in advanced trachoma, and to define biomarkers for progressive disease to assess interventions. This knowledge would support development of future control strategies such as anti-scarring treatments and an anti-chlamydial vaccine.Study Outlines:Case-control study of subjects at different stages of trachoma to characterise their conjunctival immune and fibrogenic gene expression responses by quantitative RT-PCR.Cohort study, following subjects with conjunctival scarring / trichiasis for two years for clinical evidence of progression; investigating associations between infectionand immuno-fibrogenic gene responses, to identify biomarkers for progression.Cohort study, lasting two years to identify immune and fibrogenic mechanisms associated with post-operative recurrent trichiasis, which might besuitable targets for anti-scarring treatment.Cohort study, to measure the effect of three rounds of annual mass antibiotic treatment on biomarkers for progressive scarring.

Amount: £1,095,025
Funder: The Wellcome Trust
Recipient: London School of Hygiene & Tropical M...

Key aspects of population health in post-transition Russia: mortality, fertility, health care and workforce health. 29 Nov 2005

Increasing mortality and declining fertility together mean that the population of Russia is steadily declining, with important geopolitical implications. The immediate causes of many premature deaths are increasingly understood, alcohol plays a crucial role, while ecological studies also highlight the role of economic change. Other research highlights the failure of the health system to respond effectively. There is, however, a lack of detailed information on underlying social and economic factors over time. What is the pathway from health to premature death? Why do people decide not to have children? Why do many with chronic diseases not obtain effective care? The proposed study seeks to fill this gap by exploiting the Russian Longitudinal Monitoring Study, a quasi-panel survey, with detailed information on respondents' social and economic characteristics, life events, and social support. Specifically, by tracking the characteristics of individuals over time, it will identify socio-economic determinants of: Low fertility, including birth control and childbearing patterns; Mortality, focusing on cardiovascular disease; Access to health care and use of medications. Premature retirement and sickness absence in the workforce The proposed study builds on extensive research in the host institution and links directly to ongoing policy dialogues in Russia.

Clinical epidemiology of HSV-2 and the impact of interventions against sexually transmitted infections to reduce HIV incidence in high risk women from gold mining communities in Tanzania. 27 Oct 2005

1.     In sub-Saharan Africa high risk women (HRW) who engage in sex for money, also known as female sex workers (FSW), and their clients are most at risk of acquiring HIV infection and sexually transmitted infections (STIs). STIs are likely to be particularly important co-factors for acquisition of HIV in HRW. Development and evaluation of new strategies to control both ulcerative and non-ulcerative STIs in order to reduce HIV incidence in high risk populations are urgently needed. The role of Herpes simplex virus type 2 (HSV-2) as a cause of genital ulceration is increasingly recognised. However, there are few current data on the aetiology of genital ulcers in this population or on the clinical epidemiology of HSV-2 or whether anti-herpetic treatment would reduce HIV incidence. This project therefore proposes to conduct 4 inter-linked studies in NW Tanzania: A study of the current aetiology of genital ulcers will be done in STI clinic attenders presenting with symptomatic genital ulceration. A placebo-controlled trial of monthly azithromycin and metronidazole and/or HSV-2 suppressive therapy with valaciclovir as a strategy to reduce HIV incidence, HSV-2 and HIV viral shedding and STI prevalence will be carried out in a cohort of HRW. The effects of these interventions on HIV incidence in discordant regular sexual partners of HIV-positive women will also be examined. The interaction between HIV and HSV-2 shedding will be examined in a sub-group of HRW.

Socio-cultural, economic and health system factors that determine access to subsidized ARV in southeast Nigeria: A socio-economic and policy analysis. 15 May 2008

Since the advent of ARV drugs for the treatment of HIV/AIDS patients, there exists now a high hope of survival for people living with HIV/AIDS all over the world. The problem of accessing these drugs has remained the greatest challenge particularly in the developing countries where poor HIV/AIDS patients are unable to access these drugs. The Federal Government of Nigeria initiated the National Antiretroviral Drug Access Programme to ensure that the ARV drugs reach those patients that need them at no financial cost. Despite this, ENSACA (2007) reports that the unmet need for ARV treatment is still enormous. It is therefore, necessary to explore the overall implementation process to know the problems facing the beneficiaries who access these drugs at the facility level. Hence we need to know the household and community factors, service delivery, and policy factors that constrain or enable equitable access to ART at the facility, and how the level of influence of different actors could be synergized for increased equitable access to ART. The methods to be employed in the research will be the qualitative and quantitative methods. The analysis will be carried out using Atlas ti software packages for the qualitative method and SPSS and STATA for the quantitative. The study will develop strategies for improving provision, access and use of ART.