Electrical Impedance Tomography (EIT) is a novel medical imaging method in which tomographic "slice" images are rapidly produced using rings of electrodes placed around the body. It is safe, portable and inexpensive. The principal applicant's group has demonstrated that EIT can rapidly image functional brain activity in neurological conditions like stroke, epilepsy and normal activity in animal models and has developed systems which work well in head-shaped tanks. Thrombolytic "clot-busting" treatment is a new treatment for acute stroke which must be given within three hours, but its take-up has been restricted because it is essential to undertake imaging of the head before it can be administered. This is because a sudden onset of weakness or disability which appears as a stroke, can be due to insufficient blood to a part of the brain or else bleeding into the brain. The clot-dissolving agent cannot be given until imaging has been used to assess if a bleed has occurred, as it could make the bleeding much worse with catastrophic consequences. EIT has the potential to provide an inexpensive portable unit for use in ambulances or GP surgeries which would revolutionise administration of this drug in acute stroke by providing imaging at the point of contact. This could be relayed over the internet to a radiologist who could then give permission for a paramedic to give the drug in the ambulance or in a remote centre. The plan is to make three technical improvements in imaging and design of a helmet or headnet containing the contacts needed for accurate brain EIT and test these objectively in tanks, anaesthetised rats and human patient studies. The final outcome will be a new EIT system design optimised for imaging in acute stroke, with rigorous evaluation of its performance in about 30 patients.

Vaccines are the most successful public health initiative of the 20th century. They save millions of lives annually, add billions to the global economy and extended life expectancy by an average of 30 years. Even so, the UN estimates that globally 6 million children each year die before their 5th birthday. While vaccines do exist to prevent these deaths, it is limitations in manufacturing capacity, technology, costs and logistics that prevent us for reaching the most vulnerable. The UK is a world leader in vaccine research and has played a significant leadership role in several public health emergencies, most notably the Swine Flu pandemic in 2009 and the recent Ebola outbreak in West Africa. While major investment has been made into early vaccine discovery - this has not been matched in the manufacturing sciences or capacity. Consequently, leading UK scientists are forced to turn overseas to commercialise their products. Therefore, this investment into The Future Vaccine Manufacturing Hub will enable our vision to make the UK the global centre for vaccine discovery, development and manufacture. We will create a vaccine manufacturing hub that brings together a world-class multidisciplinary team with decades of cumulative experience in all aspects of vaccine design and manufacturing research. This Hub will bring academia, industry and policy makers together to propose radical change in vaccine development and manufacturing technologies, such that the outputs are suitable for Low and Middle Income Countries. The vaccine manufacturing challenges faced by the industry are to (i) decrease time to market, (ii) guarantee long lasting supply - especially of older, legacy vaccine, (iii) reduce the risk of failure in moving between different vaccine types, scales of manufacture and locations, (iv) mitigating costs and (v) responding to threats and future epidemics or pandemics. This work is further complicated as there is no generic vaccine type or manufacturing approach suitable for all diseases and scenarios. Therefore this manufacturing Hub will research generic tools and technologies that are widely applicable to a range of existing and future vaccines. The work will focus on two main research themes (A) Tools and Technologies to de-risk scale-up and enable rapid response, and (B) Economic and Operational Tools for uninterrupted, low cost supply of vaccines. The first research theme seeks to create devices that can predict if a vaccine can be scaled-up for commercial manufacture before committing resources for development. It will include funds to study highly efficient purification systems, to drive costs down and use genetic tools to increase vaccine titres. Work in novel thermo-stable formulations will minimise vaccine wastage and ensure that vaccines survive the distribution chain. The second research theme will aim to demystify the economics of vaccine development and distribution and allow the identification of critical cost bottlenecks to drive research priorities. It will also assess the impact of the advances made in the first research theme to ensure that the final cost of the vaccine is suitable for the developing world. The Hub will be a boon for the UK, as this research into generic tools and technologies will be applicable for medical products intended for the UK and ensure that prices remain accessible for the NHS. It will establish the UK as the international centre for end-to-end vaccine research and manufacture. Additionally, vaccines should be considered a national security priority, as diseases do not respect international boundaries, thus this work into capacity building and rapid response is a significant advantage. The impact of this Hub will be felt internationally, as the UK reaffirms its leadership in Global Health and works to ensure that the outputs of this Hub reach the most vulnerable, especially children.

Biomedical imaging has a crucial role in (pre)clinical research, drug development, medical diagnosis and assessment of therapy response. Often, the images are tomographic: from the measured data, (stacks of) slices or volumes representing anatomical and functional properties of the patient can be reconstructed using sophisticated algorithms. Increasingly, images from multiple types of systems such as Magnetic Resonance (MR), radionuclide imaging using Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) and X-ray Computed Tomography (CT) are analysed together. Image quality is critically dependent on image reconstruction methods. Development and testing of novel algorithms on patient data require considerable expertise and effort in software implementation. In our previous CCP on synergistic reconstruction for PET-MR, we created a network of UK and international researchers working towards integrating image reconstruction of data from integrated, simultaneous, PET-MR scanners. New multi-modality systems are now available or under development, for instance SPECT-MR or even tri-modality PET-SPECT-CT systems. At the same time, top-of-the-range multi-modality systems are expensive and instead combining single-modality scans from different time-points and systems can provide more cost-effective solutions in some cases. Synergistic image reconstruction aims to exploit the commonalities between the data from the different modalities and time points. However, cross-modality methods are particularly challenging. We will therefore extend the network to exploit synergy in multi-modal, multi-contrast, multi-time point information for biomedical applications, concentrating on the logistical and computational aspects of synergistic image reconstruction. The Open Source Software platform to be provided by this CCP will be an enabling technology which removes the frequent obstacles encountered when working with the raw medical imaging datasets, accelerating innovative developments in image reconstruction, and ultimately enabling the possibility of synergistic image reconstruction by establishing validated pipelines for processing raw data of multiple data-sets.

Evolution over the eons has made Nature a treasure trove of clever solutions to sustainability, resilience, and ways to efficiently utilize scarce resources. The Centre for Nature Inspired Engineering will draw lessons from nature to engineer innovative solutions to our grand challenges in energy, water, materials, health, and living space. Rather than imitating nature out of context or succumbing to superficial analogies, research at the Centre will take a decidedly scientific approach to uncover fundamental mechanisms underlying desirable traits, and apply these mechanisms to design and synthesise artificial systems that hereby borrow the traits of the natural model. The Centre will initially focus on three key mechanisms, as they are so prevalent in nature, amenable to practical implementation, and are expected to have transformational impact on urgent issues in sustainability and scalable manufacturing. These mechanisms are: (T1) "Hierarchical Transport Networks": the way nature bridges microscopic to macroscopic length scales in order to preserve the intricate microscopic or cellular function throughout (as in trees, lungs and the circulatory system); (T2) "Force Balancing": the balanced use of fundamental forces, e.g., electrostatic attraction/repulsion and geometrical confinement in microscopic spaces (as in protein channels in cell membranes, which trump artificial membranes in selective, high-permeation separation performance); and (T3) "Dynamic Self-Organisation": the creation of robust, adaptive and self-healing communities thanks to collective cooperation and emergence of complex structures out of much simpler individual components (as in bacterial communities and in biochemical cycles). Such nature-inspired, rather than narrowly biomimetic approach, allows us to marry advanced manufacturing capabilities and access to non-physiological conditions, with nature's versatile mechanisms that have been remarkably little employed in a rational, bespoke manner. High-performance computing and experimentation now allow us to unravel fundamental mechanisms, from the atomic to the macroscopic, in an unprecedented way, providing the required information to transcend empiricism, and guide practical realisations of nature-inspired designs. In first instance, three examples will be developed to validate each of the aforementioned natural mechanisms, and simultaneously apply them to problems of immediate relevance that tie in to the Grand Challenges in energy, water, materials and scalable manufacturing. These are: (1) robust, high-performance fuel cells with greatly reduced amount of precious catalyst, by using a lung-inspired architecture; (2) membranes for water desalination inspired by the mechanism of biological cell membranes; (3) high-performance functional materials, resp. architectural design (cities, buildings), informed by agent-based modelling on bacteria-inspired, resp. human communities, to identify roads to robust, adaptive complex systems. To meet these ambitious goals, the Centre assembles an interdisciplinary team of experts, from chemical and biochemical engineering, to computer science, architecture, materials, chemistry and genetics. The Centre researchers collaborate with, and seek advice from industrial partners from a wide range of industries, which accelerates practical implementation. The Centre has an open, outward looking mentality, inviting broader collaboration beyond the core at UCL. It will devote significant resources to explore the use of the validated nature-inspired mechanisms to other applications, and extend investigation to other natural mechanisms that may inform solutions to problems in sustainability and scalable manufacturing.

This proposal aims at developing advanced radiation detector materials for Time of Flight Positron Emission Tomography (ToF-PET) imaging by exploiting the novel concept of high performance multi-material radiation sensing heterostructures. These heterostructures will contribute to the development of next generation imaging technologies for diagnostic, monitoring and therapeutic applications, specifically, by substantially improving the capabilities of ToF-PET technology. These heterostructures will enable i) enhanced diagnostic power; ii) reduced risk to patients (dose efficiency); iii) increased procedural flexibility (i.e. planning of radiation dose strategies and reduced examination time); and eventually iv) direct ToF-PET imaging by rendering the currently time-consuming post-acquisition reconstruction stage obsolete. This effort will be supported by multi-disciplinary facilitation of the design, fabrication and characterisation of the heterostructures, in order to develop an advanced detector material solution for use in current and future ToF-PET detector modules. The output and impact of the research will be maximised through functional testing of the proposed heterostructure detector module. The proposal matches the aspirations of the EPSRC's Healthcare Technologies research theme by i) optimising treatment and care through effective diagnosis, patient-specific prediction and evidence-based intervention; ii) supporting the development of technologies to enhance efficacy, minimise costs and reduce risk to patients; and iii) bringing together a multidisciplinary team with expertise in material science, precision engineering and instrumentation, who will be further supported by external advisors, ToF-PET experts and industrial partners for providing guidance and ensuring the transformational impact of the proposed effort.