devinitorg/iati-policy-markers huggingface dataset:
Newton001 Genetic and Electronic Medical Records to predict outcomes in Heart Failure patients - Bridging Brazilian and UK genetic epidemiology Heart failure (HF) is the main cause of hospitalization based on available data from approximately 50% of the South American population. Moreover, infectious diseases such as Chagas disease and rheumatic heart disease, known causes of HF, are still frequent in this population. Strategies are required to reduce risk and predict the future burden of this disease. The working group focuses on the development and implementation of algorithms for validation and application of medical decision routines using genetic information and electronic medical record systems in order to help the clinical management of heart failure patients.  The Brazilian group is already performing data collection and development of an integrated biobank merging demographical, clinical and genetic information. The British group will establish collaborative arrangement in cardiovascular genetics and the development and application of computational tools and quantitative methods and models for the Brazilian heart failure population with expected results leading to biomarker discovery for aetiology, treatment response and integration analysis of genomics, metabolomics and proteomics. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Characterization of Leishmania-Specific T cells in human skin and blood during cutaneous and mucocutaneous leishmaniasis Parasites belonging to the genus Leishmania are among the most diverse of human pathogens, both in terms of geographical distribution and in the variety of clinical syndromes caused by them. Currently, 12 million people are infected worldwide in 88 tropical/subtropical countries, 2 million new infections are reported annually, and 350 million people are under infection risk. In the past decade, the number of cases in endemic areas has increased sharply. In addition, leishmaniasis is spreading to several non-endemic areas of the world due to coinfections with HIV. Control measures currently available are case detection and treatment with drugs, which are expensive, not always available and cannot be self-administered. The problem is further aggravated by the surge of drug resistance parasites necessitating the development of an anti-Leishmania vaccine or other immunological therapies urgent. Research has demonstrated the importance of the immunity in controlling both cutaneous and mucocotaneous leishmaniasis, however the majority of this work has been performed on blood samples taken from patients and not from the site of infection at the skin.  In this context, the current project aims to characterize the immune mechanisms involved in controlling Leishmania in both the blood and the skin. In this proposal, we aim to apply this established approach for the first time in studies with human localized cutaneous (LCL) and mucocutaneous leishmaniasis (MCL) in order to understand the immune mechanisms associated to cell development, function and regulation in the skin and blood. Through this work we will be able to identify in detail components of the cutaneous and systemic immunity that are involved during infection and determine which of these factor can drive lesion development or/and parasite control. The results will also provide important data that will increase the understanding of Leishmania immunity providing explanations about pathological differences observed in cutaneous and mucocotaneous leishmaniasis patients and contribute to the improved design of future vaccines and drug target. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001 Understanding Antimicrobial Resistance Mutations in Tuberculosis: Towards Personalised Treatment to Combat Multi-drug Resistance Tuberculosis is recognised as one of Brazil's leading infectious diseases, with over 70,000 cases notified each year. There has been a significant increase in the number of diagnosed Multidrug resistant TB cases, with 10% of those also resistant to the two most important second---line class drugs (XDR-TB). This project aims to build upon existing collaborative programs on understanding effects of mutations, and on combating multidrug resistant and extensively drug resistant (MDR and XDR respectively) tuberculosis (TB). The two nodes, Brazil and UK, have complementary skills that encompass epidemiology, human and pathogen genetics, bioinformatics, structural biology and drug discovery. This multidisciplinary combination will facilitate the development of a novel platform to rapidly identify resistant TB from genomic sequencing. Novel mechanisms of drug resistance in TB will be explored using cutting edge techniques and correlated with clinical outcomes. This will help guide more suitable patient treatment, public health policies and future drug discovery efforts, with potential to bring benefit to individuals and public health in Brazil and UK, providing solutions to a problem that affects a third of the world's population. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Understanding pharmacokinetic - pharmacodynamic determinants of outcome to inform dose optimisation for non-MDR TB re-treatment patients in Vietnam TB remains a major global public health problem burden, with 9.6 million new cases and 1.2 million deaths in 2014. Vietnam is ranked 12th among the 22 highest TB burden countries (TB). 140 new cases were reported per 100,000 population in 2014. National TB Control Programme data indicates that 6 months of first-line month therapy for new TB patients is not successful in 10% of cases (some patients are still unwell at the end, and others relapse after apparent cure). Only 20-30% of unsuccessful treatments can be attributed to major problems with antibiotic resistance, which requires specialist management. The remainder go on to receive a standard "Category 2" treatment regimen, which is internationally approved but has not been carefully studied. Unfortunately, re-treatment patients on this regimen do not always do well; in Vietnam, the Category 2 regimen results in only 60-75% treatment success.  The reason why patients may fail two rounds of treatment is not well understood.  One reason could be that the levels of drug in the body (a study known as pharmacokinetics) of some patients is too low to kill the infection.  This problem could also be worsened by the fact that the drug levels required to kill the bacteria causing TB (known as Mycobacterium tuberculosis) are not the same in every patient i.e. some patients are infected with a strain of the M. tuberculosis bacteria which can survive higher concentrations of drugs than others.  In this project we will focus on the retreatment patient group to determine whether clinical outcome can be explained by measuring individual patient drug levels and carefully studying the ability of TB drugs to kill M tuberculosis. The project will use advanced analytical techniques to measure drug level in patient's blood samples and a number of new laboratory techniques to study how well the drugs kill each M. tuberculosis strain.  All of this information will then be combined and analysed using mathematical models to; (i) determine whether the laboratory/analytical measurements can explain the low treatment success rates and (ii) determine whether this information can be used in the future to improve treatment by predicting bad outcomes at an early stage and recommending a better drug course.  Data obtained from this study will be shared with other researchers working on TB around the world and will contribute to the wider discussion on tackling TB by designing better treatment.  Significantly, this project aims to also increase the local capacity for advanced studies of this type by providing training and mentoring to our Vietnamese colleagues in all of the methodological areas described. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Transmission dynamics and molecular epidemiology of arboviruses in Indonesia Large scale outbreaks of dengue virus (DENV) and dengue haemorrhagic fever are reported every year in Indonesia. In addition, Chikungunya virus (CHIKV) is endemic in parts of Indonesia, and two positive cases of Zika virus (ZIKV) have been described, one from an Australian who travelled to Indonesia, a second from Jambi province. DENV, CHIKV, and ZIKV are all transmitted by the mosquito Aedes aegypti, and are co-circulating in the same population. They also cause overlapping symptoms in adults, and hence are difficult to differentiate by symptoms alone. Indonesia has a large population - around 250 million people - with around 90% of the population living in areas suitable for the transmission of 'arboviruses' (short for arthropod-borne viruses), and collectively, arboviruses represent a major public health concern in Indonesia. The number of cases varies both geographically and over time, and relatively little is known about the drivers of this variation in Indonesia.  DENV, CHIKV, and ZIKV are all RNA viruses, which evolve at a high rate. Consequently, these viruses are genetically variable, and through the application of statistical models to viral sequence data, information on the dynamics of transmission, both over time and space, can be obtained. However, although the number of arbovirus infections per year is high, the number of viral sequences from Indonesia is relatively low, and often, these sequences only span a small part of the viral genome.  This project aims to characterise the transmission dynamics of DENV, CHIKV, and ZIKV through viral sequencing of clinical samples from humans.  We will harness a network of collaborators to provide archived samples, and prospective studies in locations representing west (Sumatra - Palembang City), central (Kalimantan - Banjarmasin city), and east (Maluku - Ambon city) Indonesia. In addition, we will study outbreaks that may occur during the study period. Using next-generation sequencing platforms, we aim to generate a large dataset of full-length viral genomes that will significantly add to the existing body of viral sequence data currently available.  Sequences of DENV and CHIKV (and potentially ZIKV) will be analysed using a 'phylodynamic' approach, integrating the sequence data with epidemiological data using mathematical models in order to gain a more complete understanding of the transmission dynamics of these arboviruses. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001:  Research and Training in Leishmaniasis, a Neglected Tropical Disease of Public Health Importance in Brazil Leishmaniasis is a neglected tropical disease with strong and complex links with poverty. The burden of leishmaniasis falls disproportionately on the poorest segments of the global population, including within Brazil, where there are 30,000 cases/year. Leishmaniasis diagnosis and treatment are expensive and many of the drugs used are not fit for purpose; drug resistance is an increasing problem. Public investment in treatment and control would decrease the leishmaniasis disease burden and help to alleviate poverty, yet more research is required to facilitate implementation.  This project aims to increase capacity in Brazil for early phase drug discovery by enhancing research links between the UK and Brazil in the molecular, cell and immunobiology of Leishmania parasites. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001:  Characterisation of Adult Stem Cells and the initiation of an Adult Stem Cell Bank Most adult tissues contain a population of stem cells called mesenchymal stem cells or pericytes, that are normally found surrounding capillaries.  These stem cells can give rise to a number of different cell types, including cartilage and bone, that can be used to repair damaged or defective tissues in the body.  The pericytes found in the head and neck, including those found within teeth, appear to be different to those of the rest of the body, and may be able to give rise to a wider range of different tissues, for example, nerve tissues, which makes them of interest in developing new treatments for a variety of diseases.  We propose therefore to characterise in detail the pericytes found within teeth, in the dental pulp, as an example of those in the head and neck, and compare them with the pericytes found in other parts of the body.  Fat is a very convenient source of pericytes since it contains a large number of these cells and is often removed surgically.   We will look at the overall pattern of genes which are expressed in these two populations of pericytes, to determine what the exact differences between them might be, and in parallel, we will compare the ability of the two types of pericyte to give rise to a range of different cell types that could be useful in the clinic,  for example, bone, cartilage, muscle, nerves and pigment cells.  If the two types of pericyte do show differences in the types of tissues they can produce, we will ask whether we can explain these differences based on any differences we observe in the patterns of genes expressed in these cells.  The value of this is that around the world, scientists and clinicians are interested in creating banks of these pericytes, so that they are available when needed by any suitable patient.  The pericytes obtained from fat are a very convenient source of cells to store in such banks, but if the pericytes from dental pulp are able to make a wider range of useful tissues, then we should clearly be including these cells in the bank in addition to those from fat. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Trypanosomatid protein synthesis as a target for novel drug therapies Trypanosomatids are eukaryotic parasites that migrate between insect vectors and mammalian hosts. They cause a number of highly debilitating and potentially fatal zoonotic diseases with major impacts on human health (and life-span) on a global scale. Trypanosoma cruzi, which causes Chagas disease, is believed to affect approximately 11 million people in Mexico, Central America and South America. There is currently no vaccine against Chagas disease, and the available antiparasitic treatments are unpleasant and not fully effective. Moreover, resistance to the commonly used azole- and nitro- derivative drugs is rising. Leishmania is spread by sandflies in South America, southern Europe, the Middle East, Asia and Africa, and causes three types of disease (cutaneous, mucocutaneous and visceral leishmaniasis) in approximately 12 million people. Many of the drugs used against Leishmania have side effects, and resistance is on the increase. In this project, we propose to investigate the feasibility of pursuing a new route to developing drugs effective against these dangerous parasites. This route involves differential targeting of the protein synthesis machinery in the parasite so that the human (or animal) host is unaffected.  Over the two years of this project we expect to achieve a significantly enhanced level of understanding of important targets for drugs in trypanosomatids and also to have identified some candidate drugs that can be incorporated into trials in animals subsequent to this study. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001 Pregnancy in Lupus: gestational, immunological and vascular risk factors and outcomes Two of the most serious health problems facing Brazil today are childhood and motherhood mortality, which outstrip the UK by 6- and 10 -fold, respectively. The reasons for this divide are multifactorial, but shared knowledge between the UK and Brazil could feasibly impact upon these figures.  Systemic Lupus Erythematosus (SLE), often termed Lupus, is an autoimmune disorder that frequently affects women in their child-bearing years. When superimposed on pregnancy, Lupus and Lupus-like disorders (LLD) significantly increase the incidence of all major obstetric complications, including miscarriage, stillbirth, high blood pressure, premature birth and fetal growth restriction. These women are therefore a major obstetric concern, regardless of their country of origin or clinical setting.  Clinically, the optimal care, treatment and monitoring of this group are still evolving. This application seeks to harmonise and expand the research/expertise in the study and management of these pregnancies, through the active exchange of ideas, research and best practice between the UK and Brazil.  This project brings together two renowned facilities for the study of these complex pregnancies, one in Rio de Janeiro the other Manchester, both with a wealth of obstetric and rheumatology experience. In coordinating our research efforts, our joint aims are to better define the key vascular, endocrine and immunological factors which drive poor pregnancy outcome in these affected women. By standardising clinical and research protocols across centres, sharing data and study samples, current research projects will be enhanced and joint initiatives developed. Moreover, by maximising clinical practice across centres, the stratification of SLE/LLD patients according to their pregnancy risk will be improved, with potential immediate benefits in patient care and clinical guidelines. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
PRH/HHEX in intrahepatic cholangiocarcinoma, disease progression and response to chemotherapeutics. Cholangiocarcinoma is cancer of the bile ducts that carry bile from the liver to the gall bladder and the small intestine. The number of cases of Cholangiocarcinoma is increasing year by year as is the number of deaths caused by this disease. There are several established risk factors for Cholangiocarcinoma including chronic Hepatitis B and C infection, autoimmune-related diseases such as Primary Sclerosing Cholangitis (PSC), and, in some countries, liver fluke infection. In most cases the disease is very advanced at the time of diagnosis and only around 30% of patients are suitable for surgery. New treatment options and biomarkers that allow early detection and/or inform personalised cancer treatment for individual patients are urgently needed. Under normal circumstances cell proliferation, cell-cell contacts and cell movement are carefully controlled and a large part this control is brought about by proteins called transcription factors that determine which genes are turned on or off in our cells and thereby determine how each cell behaves. We are studying a transcription factor called PRH/HHEX that is essential for liver and bile duct formation because this factor can inhibit many important pathways in the cell that are known to be required for cancer cell division and movement. In this project we will investigate the importance of PRH in cholangiocarcinoma. Using samples taken from patients with cholangiocarcinoma we have already shown that PRH levels are reduced in cholangiocarcinoma cells. The aim of this project is to investigate this in more detail using a larger number of samples. We will also identify genes that are regulated by PRH in cholangiocarcinoma cells and we will determine whether the products of these genes, or PRH itself, can be used as biomarkers to predict how quickly the cancer will progress or even allow us to identify people at risk of developing cholangiocarcinoma before they show symptoms of the disease. We will also determine whether changes in PRH activity alter the ability cholangiocarcinoma cells to form tumours in mice and we will examine whether changes in PRH these cells makes them more or less sensitive to drugs that are used to treat this disease. Finally we think that the re-establishment of PRH activity in cholangiocarcinoma could be a useful strategy for cancer treatment. We will test this using drugs that prevent protein modifications that we have previously shown to result in PRH inactivation and PRH degradation. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001-Developing a partnership to inform UK-Brazil TB control:Investigating BCG vaccination efficacy following latent TB treatment (TBTVacc) Tuberculosis (TB) is a major cause of the global disease burden. We plan to investigate whether the human immunity to tuberculosis as a result of BCG vaccination is different after individuals complete treatment for latent TB.  This will allow us to test whether BCG can protect individuals following clearance of the tuberculosis bacterium. We would develop a partnership between UK and Brazilian researchers to undertake the following:    Review and summarise any published studies of BCG assessing protection after treatment for latent TB. We will use this information and expert views to try and quantify the impact of vaccinating people after TB treatment.  We would organise two workshops, one in Brazil and one in the UK that strengthen the existing collaboration between partners. We will use these workshops to develop our pilot study and to plan the grant application for a major trial.  We would ensure there are training opportunities in the UK for Brazilian students, and UK students in Brazil.  We will undertake a pilot study in Brazil to investigate the feasibility of undertaking a trial over a 6 month period. The pilot study would examine immunological changes after BCG vaccination in 40 people immediately following the completion of treatment for latent TB. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.