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      "title_narrative":["A mathematical modeling framework for tuberculosis burden estimation and economic evaluation of pharmaceutical interventions"],
      "description_narrative":["Tuberculosis (TB) is a major cause of disease and death globally. In 2015, WHO estimated there were 9.6 million TB cases and 1.5 TB deaths. Nearly 500,000 of these cases were resistant to two or more of the main drugs used to treat TB. New drugs, and combinations of drugs, are being developed to treat tuberculosis, as are new vaccines that may protect against disease in adults.  Quantifying the burden of TB is fundamental to understanding its global epidemiology and for making appropriate resource allocation decisions. Most estimates of new TB case numbers each year rely strongly on the number of cases reported by countries in that year to WHO. Unfortunately, one in three TB cases are thought to go either undetected or unreported, so the number of cases reported underestimates the number of new cases. While one can correct for this, it is hard to know exactly how much to adjust the reported numbers. Some countries have good systems for recording causes of deaths, which can be used to estimate the number of deaths caused by TB. Increasingly, large and expensive prevalence surveys are being used to estimate the number of people with active disease in a population. These estimates are less subject to bias, but measure a different quantity. Little work has explored the best way of combining these three data sources.  A major goal of this work is to use mathematical transmission models for burden estimation and provide a unified framework for all data. These models yield the number of new cases, deaths, and also the prevalence of disease. They explicitly represent disease transmission and so introduce a dependence between the number of new cases in different years. These models involve parameters evidenced from previous epidemiological work, but must be calibrated to learn from data on TB reports, deaths and prevalence. Calibration means adjusting imperfectly known model parameters in order to match observed model outputs to the data. This process provides a model that may be used to make predictions about burden, but may also teach us something about the underlying processes. Many of the parameters concerning the epidemiology and disease course of TB are quite uncertain, and this uncertainty is rarely represented fully in models needing calibration, but will be done in this project using statistical techniques that also allow comparison of different models' performance.   TB burden estimation and calibration of transmission models are almost always carried out on a country-by-country basis. Many parameters describing disease progression are likely to be similar in different countries, even if their exact values differ for unknown reasons. Hierarchical modelling techniques allow such parameters to be correlated between countries. This can improve precision, particularly for countries with little data, as estimates can be informed by data from neighbouring countries. I will explore these techniques for the transmission model, and also in statistical modelling aiming to account for the observed patterns of drug-resistance. The transmission model will ultimately be extended to include different types of drug resistance.  As new treatments and vaccines emerge, those with responsibility for public health will want to understand the potential impact these new technologies can have in terms of gains in health, and changes in spending. Producing cost-effectiveness and budget impact evidence requires a model that includes transmission, in order to account for indirect benefits accrued by avoiding secondary cases. We will use our model to provide guidance to decision-makers seeking to maximise health gain with limited resources. We will also analyse sources of uncertainty in the model to identify future research that would have most value in increasing the precision of burden estimates and in reducing decision uncertainty around the introduction of new interventions.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["Feasibility of a cluster randomised trial of a nutritional intervention to improve outcomes after cancer surgery in low-income countries"],
      "description_narrative":["THE PROBLEM: For many types of cancer, high quality surgery is the only cure. This is particularly true in low-income countries where treatments such as chemotherapy or radiotherapy may not be available. It is important that surgery goes well. When complications occur, longer term outcomes are worse, and some patients will die. It is increasingly recognised that boosting the health of patients before surgery can greatly improve the chances of success. Of course, a balance must be struck between the urgency to operate and remove the cancer and a desire to take time and improve a patient's health. Cancer often causes extreme weight loss and, in many countries, this occurs on top of pre-existing malnutrition.   THE QUESTION: Would it be of benefit to intensively treat patients with nutritional supplements prior to surgery? Studies from high income countries suggest it could be, and the benefit may be even greater in low-income countries.  THE TEAM: We are a well-established team working to improve surgical care worldwide. Surgeons from low- and middle-income countries are supported in Research Hubs and set their own research agenda. Nutrition in cancer surgery has been identified as an area of high priority. Our team has the broad set of skills required to make this work.   OUR CURRENT WORK: We are gathering data on patients undergoing cancer surgery worldwide. It is the largest study of its kind and is taking place in 100 countries. This information will allow us to work out the relationship between malnutrition and the results of surgery in a way that hasn't been possible before. But what we really want to do is come up with a solution. This grant application is for funding to bridge the gap between our current observational study and a trial to treat patients prior to surgery. We have broad experience and are currently launching the FALCON trial, looking at steps to reduce wound infection after surgery in low-income countries.   FUTURE PROPOSED TRIAL: We want to perform a large study in low- and middle-income countries giving a nutritional supplement (sometimes called ready-to-use therapeutic food) to patients undergoing cancer surgery. We will then measure whether it results in fewer complications and better outcomes after surgery. Before we can do that, we need to do three things.   NEED FOR THIS PUMP PRIMING GRANT: First, we need to find a good way of screening patients for malnutrition in low-income countries. This is to identify those who may benefit most from a treatment. One would have thought that this would be easy and well-established, but it is not. Simple but accurate screening methods for malnutrition, which can be used by a nurse or a doctor for patients undergoing surgery, need to be developed or adapted. Second, we need to find an appropriate product. This needs to fulfil specific nutritional requirements but must be inexpensive, sustainable and ideally locally sourced. We will work with companies, experts, patients, and clinicians to find what is best. Third, we then need to make sure that a trial can actually be run. We will ask pragmatic questions such as, will there be a sufficient number of patients in our partner hospitals who can take part? Will they be able to take the nutritional supplement? Is the hospital in contact with patients after discharge to ensure we know what happens to them etc.? Determining the practicalities and planning for any problems identified is essential in ensuring the success of a study such as this.  THE BENEFIT: We propose to perform this preliminary work in a small area of our network (Ghana, Zambia, Pakistan and the Philippines), but the research promises great benefits beyond this. Focusing on fitness prior to surgery and issues such as malnutrition will be essential in improving the outcomes of cancer surgery worldwide.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "iati_identifier":"GB-GOV-13-GCRF-NE-17A-Hub-Hub2018NE-S009019-1",
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      "title_narrative":["GCRF South Asian Nitrogen Hub"],
      "description_narrative":["Humans have massively altered flows of nitrogen on our planet, leading to both benefits for food production and multiple threats to the environment. There are few places on Earth more affected than South Asia, with levels of nitrogen pollution rapidly increasing. The result is a web of interlinked problems, as nitrogen losses from agriculture and from fossil fuel combustion cause air and water pollution. This damages human health, threatens biodiversity of forests and rivers, and leads to coastal and marine pollution that exacerbates the effects of climate change, such as by predisposing reefs to coral bleaching. Altogether, it is clear that nitrogen pollution is something we should be taking very seriously.  The amazing thing is that so few people have heard of the problem. Everyone knows about climate change and carbon footprints, but how many people are aware that nitrogen pollution is just as significant?  One reason for this is that scientists and policy makers have traditionally specialised. Different experts have focused on different parts of the nitrogen story, and few have the expertise to see how all the issues fit together.  This challenge is taken up by a major new research hub established under the UK Global Challenge Research Fund. The \"GCRF South Asian Nitrogen Hub\" is a partnership that brings together 32 leading research organisations with project engagement partners from the UK and South Asia. All eight countries of the South Asia Co-operative Environment Programme (SACEP) are included. The hub includes research on how to improve nitrogen management in agriculture, saving money on fertilizers and making better use of manure, urine and natural nitrogen fixation processes. It highlights options for more profitable and cleaner farming for India, Pakistan, Bangladesh, Nepal, Afghanistan, Sri Lanka, Bhutan and the Maldives. At the same time, the hub considers how nitrogen pollution could be turned back to fertilizer, for example by capturing nitrogen oxide gas from factories and converting it into nitrate.  The fact that all the SACEP countries are included is really important. It means that lessons can be shared on good experiences as well as on whether there are cultural, economic and environmental differences that prevent better management practices from being adopted. It is also important from the perspective of international diplomacy, and provides an example to demonstrate how working together on a common problem is in everyone's interest. It puts the focus on future cooperation for a healthier planet, rather than on the past.  The South Asian case provides for some exciting scientific, social, cultural and economic research challenges. The first is simply to get all the researchers talking together and understanding each other. There are dozens of languages in South Asia, matching the challenge met when different research disciplines come together. This is where developing a shared language around nitrogen can really help. There are lots of nitrogen forms ranging from unreactive atmospheric nitrogen (N2), to the air pollutants ammonia (NH3) and nitrogen dioxide (NO2), to nitrate (NO3-) which contaminates watercourses, and nitrous oxide (N2O) which is a greenhouse gas. The impacts of each of these are being studied to provide a better understanding of how they all fit together.  The result is an approach that aims to give a much more coherent picture of the nitrogen cycle in South Asia: What is stopping us from taking action, and what can be done about it. One of the big expectations is that the economic value of nitrogen will help. India alone spends around £6 billion per year subsidising fertilizer supply. It means that South Asian governments are strongly motivated to use nitrogen better. At which point research from the South Asian hub can provide guidance on where they might start.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["Analysing the policy and governance environment for NCD control, and identifying potential policy options."],
      "description_narrative":["The Non-Communicable Diseases (NCDs) have emerged as the most important global threat to human health and wellbeing. Four major NCDs - heart disease, cancers, diabetes, respiratory diseases - cause the deaths of 38 million people every year, of whom 16 million die prematurely (under the age of 70 years). These diseases cause chronic illness and disability and are a source of suffering and financial hardship for individuals, families, communities and health systems struggling to provide continuous care for people with long-term health problems. The NCDs affect populations across the globe - and they are now the leading cause of death in many low and middle income countries.   Many of these diseases are driven by exposure to commercial products - tobacco, alcohol, highly processed foods (including the so-called 'junk foods') which have high levels of salt, sugar and/or trans-fats. Evidence shows that limiting exposure to these products is likely to bring health benefits, but it is often very difficult for individuals to sustain 'healthy behaviours' over their lifetime. Evidence-informed prevention strategies most likely to bring benefit to the largest numbers of people include: regulating exposure, e.g. taxation on products known to be health-reducing, such as sugary drinks; restricting access, e.g. no sales of tobacco to children, non-smoking zones in public spaces; or reformulating products to make them less likely to cause harm, e.g. lowering the salt content of processed foods. Such strategies, when implemented well, can have a significant impact on improving population health.   However, Governments face many challenges in implementing these policies - for example, there may be resistance from strong and powerful commercial companies that have a vested interest in selling their products. Moreover, in many countries, there is little policy experience in tackling the NCDs.   In this project we propose to undertake detailed policy analyses to identify acceptable and feasible options for Governments in both low- and middle-income countries to tackle the growing burden of NCDs in their countries. Our work will focus on three policy areas - control of sugar, salt and trans-fats in processed foods. We will work with researchers in Afghanistan, Bangladesh, Iran, Nepal, Pakistan, Tunisia and Vietnam to identify how the Government in each country is currently tackling NCDs. We will then map out the influences on policy options operating in each country. Such influences are likely to include the role of powerful stakeholders such as the food producing and selling industries, the media, the medical establishment, the Ministry of trade, etc. We will also identify whether any civil society groups (in some countries this might mean, for example, groups of parents concerned about junk-food marketing to children; in other countries it will include groups of patients suffering from diet-related NCDs such as diabetes) are working on policy issues. We will conduct interviews with key stakeholders to better understand the opportunities for seeing effective policy implemented for controlling sugar, salt and/or trans-fats, as well as identifying the challenges and barriers to putting effective policy options into operation.   This kind of health analysis requires a specific skill set which is not common in many countries. As part of our project we will therefore establish and strengthen the capacity of a network of researchers from all 8 countries (including the UK), who will support each other to carry out the analyses and interpret the findings. We will foster cross-learning of policy successes between different countries. In addition, we will promote engagement and dialogue with a wide variety of stakeholders in each country throughout the lifetime of the project in order to ensure that the findings of the research carry meaning and weight in policy decisions to improve population health both in the 7 research countries and beyond.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "title_narrative":["Interdisciplinary interventions for stunting and wasting in Zimbabwe, Zambia and Pakistan"],
      "description_narrative":["Undernutrition underlies almost half of all child deaths and has far-reaching educational, economic and health impacts. We focus on stunting and wasting, the major forms of undernutrition, which are not explained simply by shortage of food. Stunting, or reduced height, impairs long-term educational attainment and earning potential in adulthood and has multiple underlying causes, but few effective preventive strategies. Wasting in its most serious form presents as severe acute malnutrition (SAM) and children have a high risk of dying in hospital or after discharge home. For children to survive, thrive and lead prosperous lives, we need new ways to tackle undernutrition. We aim to strengthen partnerships, draw on expertise beyond traditional nutrition disciplines, and conduct a long-term programme of research in three countries with a high burden of child undernutrition - Zimbabwe, Zambia and Pakistan. Our ambition is to improve child survival, health and potential by finding new ways of preventing stunting and treating wasting, to help reach the Sustainable Development Goals.  Our long-term research programme has three aims. Our first aim is to understand the network of environmental, social and biological factors that interact to cause undernutrition so we can find the most promising targets for intervention. Our second aim is to use this learning to evaluate new strategies for undernutrition. We will design packages of interventions that are often not used together, and test their effectiveness, first in small pilot studies and then in large clinical trials aimed at preventing stunting and treating wasting. Our third aim is to use the findings we generate to influence policy and development programmes so that new interventions are scaled up effectively to reduce undernutrition.  We plan to use this current grant opportunity  to strengthen links with each country, build more south-south cooperation through collaborative meetings and a shared programme of work, and engage new investigators from outside the nutrition field. We will conduct four pilot projects to identify new approaches to undernutrition, which will start to inform our long-term programme. First, we will bring together experts in human, animal and environmental health to discuss the risks and benefits of livestock ownership for stunting and start to design a future intervention that increases the positive effects of livestock ownership whilst mitigating the negative effects. Second, we will work with social scientists to evaluate the attitudes and behaviours of mothers whose children are recovering from SAM. Strengthening the capacity of mothers to look after their children might help to deliver a package of care after discharge from hospital to improve the long-term outcomes of children with SAM. Third, we will explore whether giving high-dose vitamin D is a promising strategy to improve recovery of children with SAM in Zambia and Zimbabwe, as we recently found in Pakistan. We will measure vitamin D in our laboratory using blood samples collected from children with SAM during hospital admission and at discharge, to see whether vitamin D deficiency partly explains their poor outcomes. If so, high-dose vitamin D should be evaluated in a future trial. Finally, we will conduct a pilot study to treat maternal depression as a way of improving child growth. Poor maternal mental health can compromise caregiving and feeding practices and increases the risk of child stunting. Treatment of common mental disorders using a community-based intervention based on problem solving therapy, delivered by trained lay workers, is highly effective but is mostly used in urban areas currently. We will conduct pilot work to see if this intervention works for mothers in rural Zimbabwe, and whether it is a promising approach to improve child growth and development.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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