Cardiovascular diseases (CVD) have become the leading cause of mortality globally. In South Asia, high rates of CVD are observed at a younger age than in other countries causing a reduction in productive life years with severe economic consequences. High blood pressure (BP) confers the greatest attributable risk to death and disability associated with CVD. Our Wellcome Trust funded Control of Blood Pressure and Risk Attenuation (COBRA) trial (2004 to 2007) in Karachi, Pakistan, suggested the combined strategy of family based home health education (HHE) delivered by trained community health workers (CHW) plus care of individuals by trained private general practitioners (GP) to optimally manage hypertension had the most marked beneficial impact on BP compared to usual care, or single interventions. However, the COBRA intervention was designed for an urban South Asian setting, where private GPs cater to over 75% of the patients seeking care. Most of South Asia is still rural (73% Bangladesh, 64% Pakistan, 71% India, 85% Sri Lanka) where prevalence of hypertension is high and healthcare infrastructure and provider characteristics are very different compared to the urban setting. The COBRA trial did not evaluate effectiveness of strategies delivered using the public health infrastructure, or generalizability to the rural population in Pakistan. It is also not clear whether any benefit would extend to rural communities in other South Asian countries. In our ongoing COBRA-BPS feasibility study in Bangladesh, Pakistan, and Sri Lanka, we modified COBRA by developing a comprehensive "multicomponent intervention (MCI)" for effective delivery of hypertension care using the rural predominantly public primary care infrastructure. We also conducted extensive stakeholder consultation and received very favourable response for a full scale trial to evaluate MCI in 3 countries. We now propose a cluster randomised controlled trial (RCT) on 2550 adults with hypertension in 30 rural communities in Bangladesh, Pakistan and Sri Lanka, to evaluate a comprehensive MCI comprised of specifically comprised 1) home health education (HHE) by government community health workers (CHWs), 2) blood pressure (BP) monitoring and stepped-up referral to a trained general practitioner (GP) using a checklist, 3) trained public and private providers in management of hypertension and using a checklist, 4) designated hypertension triage counter and hypertension care coordinators in government clinics, 5) a financing model to compensate for additional health services including targeted subsidies. A total of 15 communities (5 in each country) will be randomised to MCI and 15 (5 in each country) to usual care in 3 countries. Individuals with hypertension will be followed for 2 years to assess whether MCI compared to usual care is more effective at lowering BP, and cost effective in terms of preventing CVD related disability and death. We will also interview stakeholders and conduct serial focus group discussions of patients on their experience with the strategy in relation to various components of MCI. If shown to be successful, our findings will be helpful in securing political commitment from stakeholders for up-scaling MCI strategies at the national level in these South Asian countries. The South-South collaboration and shared experiences will be very valuable in co-ordinating a regional action plan on NCDs with a focus on hypertension as an entry point. Our trial will provide direct evidence of the value of using comparable models and platforms for non-communicable disease management which would extend to other Asian countries with similar ethnic population and healthcare infrastructure.

Cardiovascular disease (CVD) has become the leading cause of mortality worldwide, accounting for 30% of deaths even in low- and middle- income countries (LMICs). In South Asia, high rates of CVD are observed at a younger age than in other countries, causing a greater loss of productive life years with severe economic consequences. High blood pressure (BP) confers the greatest attributable risk to death and disease associated with CVD. Our Wellcome Trust funded Control of Blood Pressure and Risk Attenuation (COBRA) trial (2004 to 2007) in Karachi, Pakistan, suggested the combined strategy of family based home health education (HHE) delivered by trained community health workers (CHW) plus care of patients by trained private general practitioners (GP) to optimally manage hypertension had the most marked beneficial impact on BP compared to usual care, or single interventions. However, the COBRA intervention was designed for an urban South Asian setting, where private GPs cater to over 75% of the patients seeking care. Therefore, the trial did not use the public health infrastructure per se, nor did it evaluate whether mid-level providers (MLP) can deliver first steps of hypertension care including prescribing first and second line anti-hypertensive medications. Most of South Asia is still rural (64% Pakistan, 85% Sri Lanka) where prevalence of hypertension is high and healthcare infrastructure and provider characteristics are very different compared to the urban setting. About 40-50% patients in rural Pakistan and Sri Lanka seek care (including prescription medications) from MLPs (visiting nurse, dispenser, assistant medical officer) at the government community clinics. Thus whether hypertension management by this cadre of MLPs is effective, especially when rolled out using government healthcare infrastructure is not known. Our proposed study is designed to answer this question in rural Pakistan and Sri Lanka. We propose a cluster RCT in 30 rural communities in Pakistan and Sri Lanka including 2500 individuals with hypertension with 2 year follow-up to evaluate the effectiveness of "triple approach" of combining intervention by 1) HHE plus 2) trained government primary health center MLP plus 3) trained private practitioners or "dual approach" of combining intervention of 1 and 2 only compared to no intervention (or usual care) on lowering blood pressure, and to determine whether these approaches are incrementally cost-effective. The delivery of care by the various public providers and the private sector is now recommended by the World Health Organization in several communicable disease control programs, such as Directly Observed Treatment (DOTS) for tuberculosis and management of malaria. However, evidence on the effectiveness of using the same platform for chronic non-communicable disease management is rather scarce. Moreover, wider discussion among the relevant stakeholders in South Asia to refine and implement the proposed activities would be beneficial, and would increase the likelihood of up-scaling the cost-effective strategies which could also be extended to other chronic diseases (and even infectious diseases) in an integrated manner that is potentially sustainable and applicable in rural settings across many Asian countries with similar ethnic populations and healthcare infrastructure. Comparing and contrasting the experiences from Sri Lanka and Pakistan should also provide valuable lessons not only for these two countries but also for other countries in the region and beyond.

A central theme in evolutionary biology is the understanding of the processes that contribute to the origin and maintenance of biodiversity. The diversity of recent species is not equally distributed among taxonomic groups and across the globe - a small number of clades accounts for a large part of the world's diversity and a number of relatively small areas with high levels of endemism are populated by unusually large numbers of species. These biodiversity hotspots comprise important systems for investigating the processes of evolutionary diversification; a prerequisite to document, explain, and conserve the diversity of life we observe today. The Southeast Asian peat swamp forests (PSF), found in the Sundaland biodiversity hotspot, are waterlogged forests that grow on a layer of dead plant material. Although PSF are one of the most threatened ecosystem, virtually nothing is known about the patterns and processes of evolutionary diversification of its endemic fauna and flora. PSF are characterized by a unique, vastly stenotopic freshwater fish community, which is adapted to highly acidic (pH as low as 3) black waters and comprises many miniature taxa and narrow range endemics many of which have only been discovered in recent years. We will use a multigene, molecular systematic approach to investigate the biogeography, phylogeography and demographic history of selected stenotopic PSF fish clades. Our project will for the first time provide an evolutionary perspective to global PSF conservation efforts. The specific aims are to, (1) reconstruct the time frame for the peat swamp forest fish diversification and test alternative biogeographic hypotheses that have long been contentious - Miocene-Pliocene vicariance vs Pleistocene dispersal among the landmasses of Sundaland, (2) identify past demographic expansions and their taxonomic, geographic and temporal correlates and thus infer the areas that might have been refugia or centres of diversification as opposed to recently colonized areas, and (3) identify regions of elevated taxonomic and genetic diversity that contribute most to the evolutionary legacy of this unique ecosystem. Anticipated results will have an immense impact on our understanding of PSF evolution and will provide an understanding of a key PSF community component, the stenotopic acidophilic freshwater fish fauna. Placing the PSF fish fauna in a historic context will positively contribute to research efforts focussing on palaeoclimate and palaeoecosystem reconstruction of Southeast Asia. The molecular phylogenetic data generated in our project will allow this unique fauna to be better used as model group for Southeast Asian peat swamp forest diversification and conservation. Our findings promise to have a major bearing on several wider issues concerning evolutionary patterns and processes, namely: (1) the effect of past geological event and climate induced changes on diversification patterns (2) the role of Pleistocene refuges in tropical biodiversity hotspots (3) the relationship between species diversity and phylogenetic diversity in hotspots (4) predictive ecological modelling and community assembly.