In the last three decades, survival of radiotherapy (RT) patients has greatly improved due to technological advances in delivery of radiation to tumour volumes. However, in spite of improvements in delivery of RT, a significant number of patients still experience severe toxicity from radiation treatment, particularly when the treatment volume overlaps with organs at risk. It was recently established that ultra-high dose rate (UHDR), known as FLASH RT, leads to remarkable reduction of normal tissue toxicity while maintaining tumour control with respect to conventional dose-rate RT. This so called "FLASH effect" was demonstrated in vivo on different animal models and different organs by delivering the total amount of radiation dose in a very short time (usually <200 ms). FLASH RT could represent a paradigm shift in modern radiotherapy with significant benefits for cancer patients and healthcare providers. However, the complexity of this new technology and the limited understanding of the underpinning radiobiological mechanisms hamper clinical exploitation. Even though the literature demonstration of the FLASH effect is growing very rapidly, the published studies may lead to flawed interpretation of data due to lack of established dosimetry methods for this new radiotherapy modality. Dosimetry at UHDR is complicated and it is essential to understand the effects that impact detector response in this radiotherapy modality. Without a clear understanding of the fundamental dosimetry issues, there is potential for significant errors and misinterpretation of research results and trials. Accurate dosimetry is crucial for the safe implementation of any radiotherapy technique and ensures best practice and consistency of treatments across different radiotherapy centres. The full clinical exploitation and optimization of FLASH RT requires a multidisciplinary approach to best solve the multiple complex challenges this field faces. The major part of solving these challenges will be through the development of metrology in measurement of dose and dose-rate for FLASH radiotherapy. This will enable validation of treatment planning for FLASH RT, commissioning of the new UHDR delivery systems, demonstration of compliance with safety requirements and support accurate radiobiological investigations.

The advent of carbon-fibre composite passenger aircraft, such as the Boeing 787 and the Airbus A350, has been primarily driven by the need to reduce structural weight. Higher operating efficiencies per revenue passenger kilometre also contribute to a reduction in environmental impact where 1 kg of fuel saved equates to a reduction of 3.15 kg of CO2 emissions. Indeed the European Union has set ambitious aircraft emission reduction targets by 2050 as the level of commercial air traffic is set to continue doubling every fifteen years. The high specific strength and stiffness, and corrosion and fatigue resistance of carbon-fibre composite materials, make them highly suitable for lightweight aerostructures. In laminated form, these superior properties are tempered by the material's relatively low through-thickness strength and fracture toughness which makes composite structures susceptible to impact damage. Carbon-fibre composites also have low electrical conductivity which necessitates the need for additional measures to ensure adequate lightning strike protection. The industry has adopted the use of a fine metallic mesh incorporated into the aerodynamic surfaces. This approach adds unnecessary weight to the structure as well as increasing manufacture and maintenance complexity. Composite materials also have low thermal conductivity which impacts on the design of anti-icing systems. In recent years, a number of research groups have explored the unique properties of nanoparticles dispersed in resin or introduced between lamina interfaces, to address these limitations. The use of carbon nanotubes (CNTs) especially, generated much excitement due their phenomenal structural and transport properties. The results to date have been highly variable and have fallen well short of expectations. This is partly due to a lack of interdisciplinary collaboration where fundamental questions, requiring input from chemists, physicists, material scientists and research engineers, were not adequately investigated. The proposed research in MACANTA aims to rectify this by bringing together a team with highly complementary expertise to increase the fundamental understanding of the influence of physical and chemical characteristics of different CNT assemblies in pursuit of developing multifunctional composites which mitigate the known shortcomings as well as providing additional functionality. A unique aspect of MACANTA is the emphasis on understanding and exploiting the different forms of CNT assemblies to best serve specific functions and integrated within a single structure. The team has the unique capability of producing very high quality CNTs, produced as highly-aligned 'forests'. These may be harnessed in this form and strategically placed between plies to increase through-thickness fracture toughness. Beyond simply dispersing within the matrix, they may also be 'sheared' to produce aligned buckypaper, drawn into very thin webs or spun into yarns, where their respective electrical and thermal conductivity will be investigated. These CNT assemblies will be assessed for improving lightning strike protection and providing anti-icing capability. The piezoresistive property of CNT webs will also be explored for in-situ structural health monitoring of adhesively bonded composite joints. The successful completion of the research proposed in MACANTA will culminate in the manufacture of a set of demonstrator multifunctional composite panels. They will represent a significant advancement in the state-of-the-art and provide a competitive advantage to interested stakeholders. It will also provide an ideal training platform for the development of skills of three postdoctoral researchers and two associated PhD students funded by QUB.

This year, the global demand for nanomaterial, which is already a multi-billion$ industry, will have grown 2.5-fold since 2012. Current nanomaterials production methods are at least 1000 times more wasteful when compared to the production of bulk and fine chemicals. Consequently there is an urgent need to develop green production methods for nanomaterials which can allow greater control over materials properties, yet require less energy, produce less waste (i.e. eco-friendly) and are cost-effective. Nature produces more than 60 distinct inorganic nanomaterials (e.g. CaCO3, Fe3O4, silica) on the largest of scales through self-assembly under ambient conditions (biomineralisation). Although biological methods for nanomaterials synthesis (e.g. using microorganisms or complex enzymes) are effective in reducing environmental burden, they are expensive, inefficient and/or currently not scalable to industrial production. We will adopt a synthetic biology (SynBio) approach, which is one of the EPSRC's core strategic themes, by harnessing the biological principles to design advanced nanomaterials leading to novel manufacturing methods. SynBio is a very powerful tool for the production of high-precision advanced functional nanomaterials and our approach marries two of the "8 great technologies for the future" ("Synthetic Biology" and "Advanced Nanomaterials"). Instead of using cells or microbes, our SynBio strategy uses synthetic molecules (SynBio additives) inspired from biomineralisation. SynBio produces a wide range of well-defined and tunable nanomaterials under mild (ambient) conditions, quickly and with little waste. Our SynBio approach offers the potential for high-yields, like the traditional chemical precipitation method, together with the precision, customisation, efficiency and low waste of biomineralisation. The bulk of research on bioinspired synthesis of nanomaterials has been performed at small scales and, although there are good opportunities for developing nanomaterials manufacturing based on bioinspired approaches, there are no reports on larger-scale investigations. Adopting a bioinspired SynBio approach, this project will enable the controlled synthesis and scalability of silica and magnetic nanoparticles (SNP and MNP) which are worth ~$11 billion globally. These methods are far more amenable to scale-up and can truly be considered 'green'. This SynBio process can reduce the manufacturing carbon footprint (by >90%), thus providing a significant cost benefit to industry.

Context: Testing how well the lung "functions" usually involves the use of breathing tests. However, these tests are extremely difficult to do reliably and accurately in newborn babies and infants. We need new imaging techniques that can help visualise the best and worst functioning areas of the lungs. In adults, x-ray and computed tomography (CT) imaging is often used to study the lungs. However, these methods pose an increased harmful radiation risk to newborns and infants. In addition, the function of the heart is normally measured by invasive methods that are not safe for newborns and infants, or echocardiography, which is technically challenging in these populations. As a result, our knowledge of newborn and infant diseases of the lung and heart is collectively poor compared to that of adolescents and adults. In particular, lung and heart problems in babies born pre-term are the major cause of death, yet remain not well understood. Objectives: The main purpose of this research is to develop safe, robust methods for imaging the lungs and heart in newborns and infants to better understand and manage debilitating diseases, in particular those related to pre-term birth. We will use magnetic resonance imaging (MRI); a safe imaging method that poses no harmful radiation risk to newborns and infants. The main objectives are as follows: - Develop MRI methods to investigate how diseases affect the lungs and heart in newborns and infants: -- Develop software to control the MRI scanner to obtain the best quality images that inform us about the structure and function of the lungs and heart in newborns and infants. -- Develop MRI hardware that is comfortable for newborns and infants and helps to improve image quality. - Test how well our developed methods and technology can detect changes to the structure and function of the lungs and heart in newborns and infant lung diseases, including diseases related to premature birth. -- Measure how well these methods can detect the causes for changes in patient's health over time as disease progresses. My research will be carried out at the University of Sheffield, a world-leading institution in MRI technique development with a unique interdisciplinary balance of scientists and clinicians to ensure that technological developments lead directly to NHS and patient benefit. Potential Applications & Benefits: The long-term benefit of this research is the potential to change the way lung and cardiac disease is managed in newborns and infants and improve patient quality-of-life. In particular, the methods we develop will help identify early signs of disease that cannot easily be identified by other methods. In addition, MRI is safe, and scanning can be repeated often to monitor disease progress or visualise the changes due to treatment. This cannot be done with CT, and will aid our understanding of diseases and help identify new ways they can be treated. We will develop these techniques for whole-body MRI scanners, of the sort available in most hospitals, which will increase accessibility of the technique to NHS clinicians nationally.

During pregnancy, the mother's immune system faces the task of protecting both the mother and her foetus. Mothers rely on nutrients to maintain their physiological condition and immune system, and also to nourish their developing offspring. A key question is: when mothers face challenges to their physiological state, how do they allocate energy to protect themselves and their offspring? When does this result in adverse outcomes, such as pre-term birth? To date, most research on pregnancy exposures involves long-term studies in humans or experiments on laboratory rodents or larger mammals. We have a solid understanding of how nutrition or infections in pregnancy influence birth timing and offspring development. Remarkably few studies have considered the interaction between nutrition and infections, potentially owing to the scale and complexity of studies involved, or because we have yet to develop a clear conceptual framework to develop testable hypotheses about this interaction. Here, I propose a project which tackles these two challenges head on: first, to develop a formal framework on the interplay between nutrition and infection in pregnancy, informed by evolutionary theory, and to test predictions using insect models of pregnancy, in parallel with analysis of datasets from contrasting human populations. I will first conduct a scoping review of human and animal model studies to identify the pathways linking nutrition, pathogen exposure and inflammatory responses in pregnant mothers, and consequences for offspring. I will then develop mathematical models to examine causality: how do energy trade-offs between defending against pathogens or nourishing offspring explain the optimal immune response across pregnancy stages? This formal framework will inform experiments in insects, which are extremely amenable with well-studied mechanisms, including highly conserved immune pathways found in vertebrates. Most research on insect immunity has focused on egg-laying Drosophila. I will use insects which experience pregnancy - tsetse flies and Pacific beetle cockroaches - to yield new insights on the complex interplay between maternal immune responses and nutrition. Both species exhibit almost mammalian pregnancy, nourishing their young with a milk-like substance from modified organs in utero. At the same time, they are evolutionary distant with contrasting diets, thus providing a unique opportunity to study both the specific and general machineries of pregnancy. I will expose pregnant females on diets varying in quantity or quality directly to pathogens, or indirectly activate their immune system. I will then measure responses of mothers and consequences for their young, in terms birth timing, body size and changes in physiology and gene expression. Lastly, I will examine patterns in two human cohort studies, in divergent contexts: the Children of the 90s study in the Bristol region, where diet quality and reported infections align with maternal socio-economic status, and data from the rural West Kiang region in The Gambia, a low-resource setting with strong seasonality in infections and food availability. I will compare how infections at different stages of pregnancy affect offspring, in terms of pre-term birth, child growth and later health, and how such effects change with maternal nutritional state. This project will provide fundamental insights into how maternal nutrition and immune responses interact to determine pregnancy outcomes and longer-term consequences for offspring, across diverse organisms. In the longer term, it can also inform policy to improve birth outcomes: for example, if immune activation in pregnancy cause an increased risk of pre-term birth, what are the nutritional interventions that could reduce this risk? Vaccines result in a mild immune response: what are the risks to mothers and offspring if administered early or late in pregnancy, and do these vary between under- or over-nourished mothers?