Mortality in children in Africa with SAM is still far higher than commonly appreciated, usually over 10% even for the 2-3 weeks that a child is in hospital if there is any sort of complication. It continues to occur even after discharge from hospital care. Several clinical trials are under way to try and find interventions to reduce this mortality, but they are hampered by the inadequacy of the tools at our disposable for measuring processes like impaired digestion, impaired absorption, failure of gut immunity, and disturbances of the balance of bacteria in the intestine. Even in highly refined health care systems these processes are difficult to assess, but in Africa this is a very tough obstacle to evaluating novel interventions. The study we propose will use stable (non-radioactive) isotope techniques to measure digestion and absorption, fluorescent tracers to measure leakiness of the lining of the gut, advanced immunology to study responses to molecules derived from bacteria in the gut, genomic sequencing to study the balance of bacteria in the gut, and advanced spectroscopy to analyse the function of those gut bacteria. In the process we will learn a great deal about children with severe acute malnutrition, and will generate new tools for analysing gut function. These tools may then, in turn, be useful for studying rare disorders of gut function in children and adults even in well-resourced countries, conditions which often require complex nutritional support and in which it is still, sadly, very hard to evaluate response to therapy.

Global change and trade with agricultural products have resulted in worldwide movement of species and created novel pests. Various fruit flies are among the most rapidly expanding species, and a small proportion of them, mostly in the family Tephritidae, turned into severe threats to food production around the globe. The Mediterranean fruit fly Ceratitis capitata is the most damaging representative of tephritids and is one of the most invasive insect pests worldwide. Fruit flies are formidable models for evolutionary studies of bioinvasions because of their very wide distribution, complex pattern of host dependence, complex mating behaviour and the large body of work on life history, host specificity, demographics, and behavioural and reproductive biology that has been established in the course of biocontrol measures. In this study C. capitata will be used for a genomic analysis to assess key parameters about dispersal, selection and mate choice that are of great importance to understand what factors drive these rapidly expanding populations and how they might be contained. Our research project has three main aims, based on a population genomics approach, to study (a) the historical path of range expansion, (b) the genetic effects of sterile insect release in biocontrol, and (c) the evolutionary impact of insecticides on the population biology. Each of these questions will greatly profit from genome-wide analysis of sequence variation using the RAD technique. Unlike conventional approaches that only sample selected, presumed neutral gene segments, genetic scans using RAD polymorphisms provide markers distributed fairly evenly across all parts of a genome. The method therefore has the advantages of whole genome sequencing, which remains prohibitive for many applications in terms of cost and data handling, but samples a proportion of the genomic variation sufficient for most purposes.

With growing land-use pressures and consequent severe soil erosion, many East African socio-ecological systems are at a tipping point. Continued and accelerating soil erosion presents a credible threat to community and ecological resilience to future climate change shocks. Soil erosion and downstream siltation problems challenge water, food and energy security, with growing threat from climate change. Even under 'normal' climatic conditions, soil erosion reduces water and nutrient retention, biodiversity and plant primary productivity on agricultural land putting stress on food production, notwithstanding ecosystem and water resource/power generation impacts downstream. This undermines the resilience of communities that depend on soil and water resources, and shocks are often amplified by physical and socio-cultural positive feedback mechanisms. Shocks can, however, lead to a learning experience that propels a system to a qualitatively different pathway. This can support greater-than-previous levels of resilience (sometimes termed 'bounce back'). Co-production of sustainable land management practises will help enable agrarian and pastoral communities to (1) withstand shock of future extreme hydro-climatic events and (2) recover from prior environmental impacts to a resilience level beyond the prior state through restoration/enhancement of degraded landscapes. Facilitating a step change in land management practice to reduce complex soil erosion impacts is a fundamental target within the UN Sustainable Development Goals, a challenge that requires an interdisciplinary approach. To bring about urgently needed change in land management practice behaviour, evidence is required to demonstrate how social resilience is intrinsically linked to landscape/ecological resilience through the coupled co-evolution of natural resource systems and dependent rural communities. The East African Rift System (EARS) region has the highest catchment sediment yields of sub-Saharan Africa linked in part to topography and rainfall but also to recent and historic land conversion to agriculture and, in particular, increasing livestock numbers on grasslands. Extreme drought and rainfall events, which are already a characteristic feature of tropical climatology (e.g., linked to ENSO), are widely accepted to increase in magnitude and/or frequency with global climate change. There is a real risk that, in the absence of community-owned soil management programmes, recent land use change will amplify hydro-climatic and consequent societal impacts. This is exacerbated by socio-cultural lock-ins such as power and esteem gained by owning livestock, putting pressure on fragile ecosystems and ecosystem services, with repercussions for economic and human health. Experts in soil erosion and land degradation problem identification are not necessarily experts in socio-economic and socio-cultural solutions. To tackle this challenge, we propose an interdisciplinary approach to designing sustainable land management practices that would enable rural communities affected by soil erosion to overcome post-erosion shocks and achieve a higher level of resilience than previously. Through novel integration of environmental science, arts and humanities and social science evidence, this project will map out potential behavioural changes and how these can be embedded in the design and implementation of soil conservation and restoration strategies. The interdisciplinary approach in this foundation-building programme will develop knowledge of complex interlinkages between soil degradation, climate change, and community resilience in the EARS region, as well as to explore pathways to possible solutions. Interdisciplinary evidence of the problem will be explored against complex socio-cultural community concerns and needs, and potential solutions will be considered with stakeholder groups to identify and underpin future behavioural change in land management.

In the UK, one in two people will be diagnosed with cancer during their lifetime and of those who survive, 41% can attribute their cure to a treatment including radiotherapy. Radiotherapy is very cost effective, accounting for only 6% of the total cost of cancer care in the UK. In radiotherapy the way the radiation dose is delivered and conformed to the tumour uses a treatment plan, which is based around a CT scan of the patient and their tumour. The treatment plan uses beams of radiation at different angles, to maximise the dose (and damage) to the tumour and to minimise the damage to the surrounding healthy tissue. Constraints are also applied for "organs at risk" which are often more sensitive to radiation and so require the dose to be as low as possible. Radiotherapy is normally delivered in fractions, with a fraction being typically 1-2 Gy. A course of radiotherapy is typically 1 fraction every week-day over a period of 4-6 weeks. Radiotherapy seeks to maximise the damage to the tumour (to sterilise it) while minimising the damage to the surrounding healthy tissue (to reduce side effects). In recent years radiotherapy has developed rapidly with the development of new machines and methodologies. These in turn, have resulted in better imaging, treatment planning and dosimetry, which enable the dose to be more accurately delivered and conformed to the tumour. This has resulted in better cancer survival and reduced side effects for patients. However, to maintain this rate of advancement and deliver even better treatments for patients we require innovation and solutions to the challenges, which still confront advanced RT. This is exactly where the STFC community can make an enormous impact, working in partnership with the clinical community, as they together they have exactly the skill set which is needed to effectively tackle these new challenges as they arise. In addition, the latest developments in radiotherapy - such as MR-linacs and proton therapy - evidence the need for the STFC community to work in partnership with the clinical community and commercial partners. If the UK is to remain competitive and deliver even better treatments for patients, and produce income and impact for the UK economy, it can no longer rely on serendipitous partnerships. This is what this Advanced Radiotherapy Network + (ARN+) seeks to address. Working actively with the clinical community through the National Cancer Research Institute (NCRI) Clinical and Translational working group on Radiotherapy (CTRad) it has been able to establish a new community drawn from across STFC with clinicians and clinical scientists from the NHS. This application is an extension of an existing successful ARN + and is aimed at both consolidating the success of the ARN+ and taking it one step further by developing a global dimension for its activities by working with the IAEA. It also seeks to showcase its activities to industry and develop a pipeline of innovation to the clinic. Finally it looks to work with STFC within the framework of UK Research and Innovation to build a national consensus, research roadmap and funding strategy in the field of Advanced Radiotherapy.

2021-2030 is the UN Decade of Ocean Science for Sustainable Development aiming at "The science we need for the ocean we want" through "Transformative ocean science solutions for sustainable development, connecting people and our ocean". In FOCUS we aim to make a significant UK contribution to the Decade through a broad body of scientific endeavour. This crosses multiple disciplines, focusing on the coastal zone and shelf seas at a global scale (the "Global Coastal Ocean") and addresses each of the seven expected Decade Outcomes: i A clean ocean ; ii A healthy and resilient ocean; iii A productive ocean; iv A predicted ocean; v A safe ocean; vi An accessible ocean; vii An inspiring and engaging ocean. The Decade works through endorsed international programmes, and NOC and PML have been involved in the co-design of several of these, notably: CoastPredict: Observing and Predicting the Global Coastal Ocean and Ocean Acidification Research for Sustainability. Alongside the UN Decade, the World Climate Research Programme is currently designing "Light House Activities" and FOCUS scientists will contribute to this, particularly on Sea Level Rise in Safe Climate Landing. Alongside these global partnerships we will work with regional partnerships, such as the SE Asia Land to Ocean Network and the Network-to-Network for the Gulf of Mexico, and many research institutions and universities around the world. Working in these partnerships, we address the fact that the global coastal ocean is under immense pressure from human instigated climate change and population growth. Climatic changes in marine temperature, circulation and acidity impact on marine ecosystems and their ability to provide 'ecosystem services' such food from fisheries and drawing down CO2 from the atmosphere. Sea level rise and increases in storminess hugely increase the risk of coastal flooding. How these climate impacts act together and relate to changes to episodic events (such as storms) is a major knowledge gap. Similarly, substantially rising human activity in the coastal zone (e.g. in growing megacities) leads to increased risk of pollution and degradation to marine environments without careful management. Many aspects, such as nutrient pollution from agriculture and sewage, have been investigated for years, but others are newly emerging, e.g. the impacts of mining waste, pollution from shipping and artificial light at night. Again, how these multiple direct human impacts act together is largely unknown. Coastal habitats, such as seagrasses, mangroves and seaweeds have the potential to draw down substantial amounts of CO2 and help stall climate change, but only if they are healthy ecosystems. Hence, understanding how the protection and restoration of these environments can improve CO2 drawdown is an important aspect in fighting climate change. Finally, to address the issues described above on a global scale requires new approaches to translating understanding from one region to another - particularly from data rich to data sparse areas. This involves developing approaches to classify the global coastal ocean, based on our understanding of oceanographic processes, and to develop ways to capture and compare the exposure of climate change risk of different sea areas. Social information can be added to this to create a whole-system view, for example, from climate to ecosystems to fisheries and to people. In FOCUS we will bring to bear the full range of oceanographic tools to address these pressing issues, including numerical models, satellite remote sensing, field surveys and laboratory work. Extensively we will reanalyse existing data from around the world in novel and innovative ways and we will engage with scientists from many regions (such as South and South East Asia and the Caribbean), to build on existing knowledge, in a spirit of mutual respect and transparency, freely sharing methods and data.