Optical 'biopsy' is a concept whereby traditional histology is replaced with non-invasive, real-time imaging techniques such as endomicroscopy. This new probe-based technology provides live microscopy images to the operator, allowing for immediate cellular tissue characterisation in situ and in vivo. With recent advances in endomicroscopy, including the latest technological progress from the EPSRC SMART-Endomicroscopy project, it is timely to address the potential of endomicroscopy for assessing gut dysfunction, particularly given the large burden of enteric disease in all countries and across different age groups. The aim of this project is to form a new translation alliance in collaboration with a leading industrial design SME (Smallfry Ltd) and the Gates Foundation, exploring applications of the new endomicroscopy/robotics technology in global health. In particular, and in line with the Gates Foundation Enteric and Diarrheal Diseases Strategy, it focuses on how low-cost (yet high impact/tech) robotic technologies can provide a practical optical biopsy system for gut disease. This rather unexpected application of our research would complement the planned pathways to impact of the original grant supported by EPSRC, making the technology relevant to both specialised and global health settings, addressing additional challenges imposed by frugal innovation.

Malaria mosquitoes mate in swarms. They use their antennal ears to detect the mating partners through their flight tones. Because the swarm is noisy, and the mosquito flight tones faint, mosquito auditory organs are highly sensitive and complex. We discovered a few years ago that the mosquito ear is innervated by a complex neuromodulatory network of neurotransmitters that are released from the brain, what is called an efferent system. This system is unique as mosquitoes are the only insect where auditory efferent activity has been described. Because mosquito hearing is necessary for mosquito reproduction, we hypothesize that disrupting the efferent system could be an innovative target for mosquito control. In the initial fellowship period, we focused on studying two of there neurotransmitters, octopamine and serotonin, to analyse their auditory roles in the swarm context and the implications for mosquito mating. For the second fellowship period, we would like to build on these results and provide a better understanding of the underlying fundamental biology mechanisms and explore implications for malaria control. We will also study the auditory role of the inhibitory neurotransmitter GABA, which extensively innervates the auditory nerve. We aim at providing a comprehensive understanding of the role of individual neurotransmitters modulating mosquito audition and swarming behaviour and of the emergent properties of the system. We will also explore specific tools to disrupt mosquito audition and swarming behaviour and model the effects on malaria transmission.

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.

In thirty years' time there will be half a billion adolescents in Africa. Like youth everywhere, they possess huge potential to thrive. But more than half are trapped in cycles of poor nutrition, poverty, low education, violence and unemployment. They also have the world's highest rates of early fertility, with adverse long-term outcomes for adolescent parents and their children. Such inter-generational disadvantage creates risks not only in the region but also to global stability. The SDGs and African Union's Agenda 2063 challenge us to take a radical new approach. The UK's Global Challenges Research Fund provides a unique opportunity to do this. The Accelerating Advantage Hub will find the combinations of services with the greatest positive impacts for Africa's adolescents and their children. We need to move beyond services focused on single outcomes, towards 'super-accelerator' impacts across multiple SDGs of health, education, violence prevention, gender equality and economic stability. With our government partners we will test combination services - for example of cash transfers, malaria prophylaxis, parenting programs, business skills and violence prevention - to identify the leanest and most effective policy packages. The Hub has been planned with African governments and international agencies including the UN Development Program, African Union, UNICEF and the World Health Organisation. They have told us that 'evidence as usual' is not enough. When we make a personal investment, like buying a computer, we want to know not only whether it is the most efficient, but also whether it is good value for money and whether we will like to use it. Governments need the same information about services: their effectiveness, their cost-effectiveness, whether they can be delivered through existing health, education and welfare systems, and whether they will be accepted by service providers and by adolescents. The Hub will conduct large-scale studies and use existing data in Angola, Cote D'Ivoire, DRC, Ethiopia, Gambia, Ghana, Guinea, Kenya, Lesotho, Liberia, Malawi, Mali, Mozambique, Nigeria, Senegal, Sierra Leone, South Africa, Somalia, South Sudan, Tanzania, Uganda, Zambia & Zimbabwe. All projects will include cost-effectiveness to assist budget decisions. In short, we will provide African policy-makers with the evidence they need and want to do the best for adolescents. The Hub will also train and support frontline workers to improve services for adolescents across Africa. We will turn evidence into training modules, freely accessible manuals and support materials. We will deliver practitioner training in 34 African countries by working with NGO partners selected for wide regional coverage, for example Paediatric Adolescent Treatment for Africa, the International Rescue Committee, Clowns without Borders and the International AIDS Alliance. Skills-building for young researchers in Africa and the UK is built into the Hub's work. We will support 45 promising young academics and dedicated African policymakers to focus their careers on improving the lives of adolescents and their children. The Hub's work is planned with adolescents themselves. Too many services have failed because they do not appeal to teenagers' aspirations and immediate goals. The Hub will work directly with adolescent advisory groups in Eastern, Western and Southern Africa to co-develop approaches that are not only effective, but also meaningful and fun for those who will use them. We aim to reach 20 million adolescents and their children with effective combinations of services to meet their needs. Between our direct countries of research and our NGO partners, the Hub will actively engage with policymakers, practitioners and adolescents across East, West, Southern and Central Africa and including fragile and war-torn states. We have a common goal: to transform the potential of Africa's adolescents into a thriving future for the continent.

The CDT will train the next generation of leaders in statistics and statistical machine learning, who will be able to develop widely-applicable novel methodology and theory, as well as create application-specific methods, leading to breakthroughs in real-world problems in government, medicine, industry and science. The research will focus on the development of applicable modern statistical theory and methods as well as on the underpinnings of statistical machine learning. The research will be strongly linked to applications. There is an urgent national need for graduates from this CDT. Large volumes of complicated data are now routinely collected in all sectors of society, encompassing electronic health records, massive scientific datasets, governmental data, and data collected through the advent of the digital economy. The underpinning techniques for exploiting these data come from statistics and machine learning. Exploiting such data is crucial for future UK prosperity. However, several reports from government and learned societies have identified a lack of individuals able to exploit this data. In many situations, existing methodology is insufficient. Off-the-shelf approaches may be misleading due to a lack of reproducibility or sampling biases which they do not correct. Furthermore, understanding the underlying mechanisms is often desired: scientifically valid, interpretable and reproducible results are needed to understand scientific phenomena and to justify decisions, particularly those affecting individuals. Bespoke, model-based statistical methods are needed, that may need to be blended with statistical machine learning approaches to deal with large data. Individuals that can fulfill these more sophisticated demands are doctoral level graduates in statistics who are well versed in the foundations of machine learning. Yet the UK only graduates a small number of statistics PhDs per year, and many of these graduates will not have been exposed to machine learning. The Centre will bring together Imperial and Oxford, two top statistics groups, as equal partners, offering an exceptional training environment and the direct involvement of absolute research leaders in their fields. The supervisor pool will include outstanding researchers in statistical methodology and theory as well as in statistical machine learning. We will use innovative and student-led teaching, focussing on PhD-level training. Teaching cuts across years and thus creates strong cohort cohesion not just within a year group but also between year groups. We will link theoretical advances to application areas through partner interactions as well as through a placement of students with users of statistics. The CDT has a large number of high profile partners that helped shape our application priority areas (digital economy, medicine, engineering, public health, science) and that will co-fund and co-supervise PhD students, as well as co-deliver teaching elements.