Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Depression in later life is common, costly, and can have devastating consequences for those affected, their relatives, and society. Notwithstanding this, it usually goes unrecognised and untreated, especially in low-middle income countries. The Brazilian population is ageing rapidly, with already 20 million people aged 60 or more. The Brazilian health care system, especially the mental health sector, is poorly prepared to meet this challenge. There is an urgent need to develop cost-effective depression treatment programmes for older people living in low- and middle-income countries. The Brazilian primary care system is an excellent setting to introduce and evaluate an intervention to reach a large proportion of this neglected part of the population. The intervention proposed (PROACTIVE) aims to overcome barriers for treating old people with depression, such as patients' social isolation and difficulties in accessing services, lack of skilled and supported staff to deliver effective interventions, and poor coordination and accountability among staff caring for elderly people. PROACTIVE will be a two-arm cluster randomised controlled trial aiming to compare the effectiveness and cost-effectiveness of adding to usual care a psychosocial, community-based intervention mostly delivered at home by Community Health Workers employed by the existing primary care system. The intervention will be compared with an 'enhanced' usual care in reducing depressive illness and improving functioning among adults 60 years or older from poor socioeconomic backgrounds in São Paulo, Brazil. Primary Care Family Health Units will be randomised to one of these two treatment groups. All or a random sample of the Family Health Teams within a Unit, depending on size of the Unit, will be invited to participate. PROACTIVE consists of 8 to 11 home sessions, depending on severity of depression, delivered over 17 weeks. The initial phase is given to all participants and comprises three sessions covering psycho-education and learning simple coping strategies to improve mood. The Second Phase is based on behaviour activation and relapse prevention strategies; the number of sessions depends on the severity of symptoms. Community Health Workers will be equipped with tablet computers to assist with the delivery and accountability of the intervention and to receive further training and supervision. Those participants who do not improve with the intervention, in relation to specified clinical algorithms, will be discussed in supervision and regular team meetings and, if needed, other clinical decisions will be adopted. The control group will receive 'enhanced' usual care in so far as improved identification and periodic assessments of high-risk cases treated as per a 'high-risk' protocol. The primary outcome measure of PROACTIVE is the 9-item Patient Health Questionnaire (PHQ-9). We will compare the recovery of cases (PHQ-9<10) across arms at 8 and 12 months after entering the trial, using an intention-to-treat analysis. Several secondary outcomes will be also measured including quality of life and levels of functioning. Direct and indirect costs in both arms will be measured to undertake a cost-effectiveness analysis. We anticipate recruiting a total of 1,440 participants registered in 20 FHUs (clusters), yielding 86.5% power for a 15 percentage point difference (25% to 40%) in recovery at 8 months. We have developed and successfully tested the feasibility and acceptability of the proposed intervention in primary care in São Paulo (RCUK/FAPESP). This project has the potential for a timely and major impact on the wellbeing of depressed older adults, further reducing dependency on specialised mental health resources already under strain in Brazil and most LMIC. The Brazilian primary care model is being replicated in several other LMIC, contributing to increase the portability of this intervention to other LMIC should its cost-effectiveness be demonstrated.

One of the factors that significantly impinges on the quality of life among elderly people is a decrease in salivary flow (hyposalivation) and a dry mouth (xerostomia). The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Xerostomia leads to problems with speech, taste digestion, mastication and swallowing, and a high incidence of dental caries and candida. There is no cure but chewing gum and artificial saliva are used to relieve the symptoms in many cases. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the mechanisms that drive xerostomia so that new therapies can be found. Xerostomia can be caused by a number of different factors. Certain medicines cause xerostomia as a side effect, while xerostomia is also a central feature of the auto-immune disease Sjögren Syndrome, which affects up to 3-4% of older adults. Xerostomia is also a feature of some genetic disorders that affect the salivary glands, such as LADD syndrome and ALSG, and is frequently a side effect of head and neck radiotherapy. We aim to study xerostomia using various mouse models of gland dysfunction and regeneration. This application aims to combine knowledge of salivary gland development with knowledge of salivary gland stem cells from mouse and translate these findings into humans. This is possible through combining research from basic scientists in the UK and clinical researchers in Brazil, with the ultimate goal of creating innovative methods to treat xerostomia.

Enteric fever caused by Salmonella Typhi and Paratyphi A is wide spread throughout the world. particularly burdensome in South-East Asia, with approximately >22 million new infections resulting in a 1% fatality rate annually. Control of the disease is hindered due to insufficient understanding of disease pathogenesis and immune responses to the infection, inaccurate diagnostic tests and limited efficacy of licensed vaccines. Thus understanding human host-responses to enteric infections is pivotal in developing improved diagnostic tests and vaccines. The Oxford Vaccine Group (OVG) has recently developed a human challenge model for S. Typhi and Paratyphi A. Briefly, human adult volunteers were orally infected with a pathogenic dose of S. Typhi and Paratyphi A and closely monitored the following days until treatment with antibiotics. This model was subsequently used to test vaccine efficacy by vaccinating participants prior to ingestion of the bacteria. The various samples collected provide a rich dataset consisting of clinical and immunological measurements invaluable to understand disease pathogenesis and human molecular responses to infection. Associated with such large datasets and different levels of data (molecular, serological and clinical) is the challenge of analysis and data integration, which we address through using systems biology approaches. Systems biology/vaccinology is an interdisciplinary field that combines systems-wide measurements, networks, and predictive modelling in the context of biology, vaccines and infectious disease. Computational modelling and integration of multiple levels of data (clinical, immunological, and molecular) develops a multi-facetted understanding of disease pathogenesis and biological mechanisms underlying host-responses to infections/vaccination. Particularly important in this context are regulatory mechanisms, which consist of complex networks involving multiple transcriptional and genetic components. Recently, it has become clear that long non-coding RNAs (lncRNAs) play a pivotal role in the regulation of biological processes by a diverse range of mechanisms. Integrative analysis of transcriptional signatures related to expression of lncRNAs allows us to identify molecular events associated with clinical and immunological outcomes. We are aiming to thoroughly integrate these different datasets to fully investigate the intricacy of human host-responses to infections. We believe that this approach is necessary in order to further shed light on the undisputed complexity of the immune system. As these samples are derived from the human host and a uniquely controlled experimental design, the results will likely elucidate important clues as to how the host reacts to enteric infections and how S. Typhi/Paratyphi A potentially modulate the host-response. By partnering with the Computational Systems Biology Lab at the University of Sao Paulo we are combining one of the largest clinical trials groups in Europe with an excellence in vaccine trials with a team of computational biologists leading in the field of systems vaccinology.