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Our life expectancy is increasing and we are outliving our skeletal tissues. There is a need for orthopaedic surgery to move from replacement of tissues to regeneration. To do this medical devices are required that can stimulate the body's own healing mechanisms. Over the last 10-15 years, tissue engineering has promised that combining engineering principles with cells will lead to regeneration of tissues, however skin is the only tissue engineered product used clinically. The reasons skeletal tissue engineering has not been successful is that materials have not been developed that fulfill all the engineering design criteria for regenerative device (scaffold) and how materials interact with cells is not fully understood. A new hybrid approach is proposed where hybrid refers to an integrated interdisciplinary approach and the innovation in materials engineering that is needed. New materials must be developed that mimic the mechanical properties and structure of natural tissues. The aim is to build an interdisciplinary research team that can deliver high impact step changes in the way tissue engineering research is carried out to make skeletal tissue engineering a clinical reality. Team members will have expertise in materials chemistry and processing, multi-scale characterisation, materials modelling, cell biology, orthopaedic surgery and technology transfer. The adventurous programme will benefit the UK by improving the quality of life of patients, increasing the efficiency of orthopaedic surgery, reducing surgical costs and boosting the UK economy by ensuring patients recover and return to work more rapidly.The core platform technology will be novel nanostructured (hybrid) materials that can be designed to stimulate bone growth or cartilage regeneration before they are remodelled in the body and replaced by natural healthy tissue. To make these complex materials a clinical reality they must be understood from the atomic through the nano to the macro level and optimised with respect to cellular response. Computer models and improved characterisation methods are needed. Bone scaffolds must stimulate stem cells to produce bone and new ways of growing cells in devices may be necessary in order for blood vessels to grow throughout bone scaffolds and for cartilage regeneration to become a reality. If new devices are to reach the clinic, technology transfer must be considered. My vision is to build and lead a world renowned research group successful in musculoskeletal tissue engineering with a new field of inorganic/ organic hybrid materials engineering at its core. The research group will attract best, internationally leading researchers to the UK (or to stay in the UK). It will involve international and UK collaborators, with the UK at the focus, placing it at the forefront of biomaterials and tissue engineering. There will be focus on developing a dynamic and supportive research environment and on developing the career of group members so they will become the next leaders of the new fields that will evolve from the group's work.

Cancer is the second most common cause of death globally, accounting for 8.8 million deaths in 2015. It is estimated that radiotherapy is used in the treatment of approximately half of all cancer patients. In the UK, one new NHS proton-beam therapy facility has recently come online in Manchester and a second will soon be brought into operation in London. In addition, several new private proton-beam therapy facilities are being developed. The use of these new centres, and the research that will be carried out to enhance the efficacy of the treatments they deliver, will substantially increase demand. Worldwide interest in particle-beam therapy (PBT) is growing and a significant growth in demand in this technology is anticipated. By 2035, 26.9 million life-years in low- and middle-income countries could be saved if radiotherapy capacity could be scaled up. The investment required for this expansion will generate substantial economic gains. Radiotherapy delivered using X-ray beams or radioactive sources is an established form of treatment widely exploited to treat cancer. Modern X-ray therapy machines allow the dose to be concentrated over the tumour volume. X-ray dose falls exponentially with depth so that the location of primary tumours in relation to heart, lungs, oesophagus and spine limits dose intensity in a significant proportion of cases. The proximity of healthy organs to important primary cancer sites implies a fundamental limit on the photon-dose intensities that may be delivered. Proton and ion beams lose the bulk of their energy as they come to rest. The energy-loss distribution therefore has a pronounced 'Bragg peak' at the maximum range. Proton and ion beams overcome the fundamental limitation of X-ray therapy because, in comparison to photons, there is little (ions) or no (protons) dose deposited beyond the distal tumour edge. This saves a factor of 2-3 in integrated patient dose. In addition, as the Bragg peak occurs at the maximum range of the beam, treatment can be conformed to the tumour volume. Protons with energies between 10MeV and 250MeV can be delivered using cyclotrons which can be obtained `off the shelf' from a number of suppliers. Today, cyclotrons are most commonly used for proton-beam therapy. Such machines are not able to deliver multiple ion species over the range of energies required for treatment. Synchrotrons are the second most common type of accelerator used for proton- and ion-beam therapy and are more flexible than cyclotrons in the range of beam energy that can be delivered. However, the footprint, complexity and maintenance requirements are all larger for synchrotrons than for cyclotrons, which increases the necessary investment and the running costs. We propose to lay the technological foundations for the development of an automated, adaptive system required to deliver personalised proton- and ion-beam therapy by implementing a novel laser-driven hybrid accelerator system dedicated to the study of radiobiology. Over the two years of this programme we will: * Deliver an outline CDR for the 'Laser-hybrid Accelerator for Radiobiological Applications', LhARA; * Establish a test-bed for advanced technologies for radiobiology and clinical radiotherapy at the Clatterbridge Cancer Centre; and * Create a broad, multi-disciplinary UK coalition, working within the international Biophysics Collaboration to place the UK in pole position to contribute to, and to benefit from, this exciting new biomedical science-and-innovation initiative.

There are more than 10 million people in the U.K., one in six, with some form of hearing impairment. The only assistive technology currently available to them are hearing aids. However, they can only aid people with a particular type of hearing impairment, and hearing aid users still have major problems with understanding speech in noisy backgrounds. A lot of effort has therefore been devoted on signal processing to reduce the background noise in complex sounds, but this has not yet been able to significantly improve speech intelligibility. The research vision of this project is to develop a radically different technology for assisting people with hearing impairments to understand speech in noisy environments, namely through simplified visual and tactile signals that are engineered from a speech signal and that can be presented congruently to the sound. Visual information such as lip reading can indeed improve speech intelligibility significantly. Haptic information, such as through a listener touching the speakers face, can enhance speech perception as well. However, touching a speakers face in real life is often not an option, and lip reading is often not available such as when a speaker is too far or not in the field of view. Moreover, natural visual and tactile stimuli are highly complex and difficult to substitute when they are not available naturally. In this project I will engineer simplistic visual and tactile signals from speech that will be designed to enhance the neural response to the rhythm of speech and thereby its comprehension. This builds on recent breakthroughs in our understanding of the neural mechanisms for speech processing. These breakthroughs have uncovered a neural mechanism by which neural activity in the auditory areas of the brain tracks the speech rhythm, set by the rates of syllables and words, and thus parses speech into these functional constituents. Strikingly, this speech-related neural activity can be enhanced by visual and tactile signals, improving speech comprehension. These remarkable visual-auditory and somatosensory-auditory interactions thus open an efficient and non-invasive way of increasing the intelligibility of speech in noise through providing congruent visual and tactile information. The required visual and tactile stimuli need to be engineered to efficiently drive the cortical response to the speech rhythm. Since the speech rhythm is evident in the speech envelope, a single temporal signal, either from a single channel or a few channels (low density) will suffice for the required visual and tactile signals. They can therefore later be integrated with non-invasive wearable devices such as hearing aids. Because this multisensory speech enhancement will employ existing neural pathways, the developed technology will not require training and will therefore be able to benefit young and elderly people alike. My specific aims are (1) to engineer synthetic visual stimuli from speech to enhance speech comprehension, (2) to engineer synthetic tactile stimuli from speech to enhance speech comprehension, (3) to develop a computational model for speech enhancement through multisensory integration, (4) to integrate the engineered synthetic visual and tactile stimuli paired to speech presentation, and (5) to evaluate the efficacy of the developed multisensory stimuli for aiding patients with hearing impairment. I will achieve these aims by working together with six key industrial, clinical and academic partners. Through inventing and demonstrating a radically new approach to hearing-aid technology, this research will lead to novel, efficient ways for improving speech-in-noise understanding, the key difficulty of people with hearing impairment. The project is excellently aligned with the recently founded Centre for Neurotechnology at Imperial College, as well as more generally with the current major U.S. and E.U. initiatives on brain research.

The Neuromod+ network will represent UK research, industry, clinical and patient communities, working together to address the challenge of minimally invasive treatments for brain disorders. Increasingly, people suffer from debilitating and intractable neurological conditions, including neurodegenerative diseases and mental health disorders. Neurotechnology is playing an increasingly important part in solving these problems, leading to recent bioelectronic treatments for depression and dementia. However, the invasiveness of existing approaches limits their overall impact. Neuromod+ will bring together neurotechnology stakeholders to focus on the co-creation of next generation, minimally invasive brain stimulation technologies. The network will focus on transformative research, new collaborations, and facilitating responsible innovation, partnering with bioethicists and policy makers. As broadening the accessibility of brain modification technology my lead to unintended consequences, considering the ethical and societal implications of these technological development is of the utmost importance, and thus we will build in bioethics research as a core network activity. The activities of NEUROMOD+ will have global impact, consolidating the growing role of UK neurotechnology sector.