Aims and Background to the research Hearing loss is the most common sensory disorder in humans with 1.5 billion people affected by this during their lifetime. Some types of hearing loss are more common as we get older and therefore the burden of hearing loss is predicted to rise further as our aging population increases. Hearing loss has a significant impact on quality of life, patient health and safety as well as placing a huge demand on increasingly stretched public health services. In order to prepare and respond to this rapidly accelerating public health crisis we need to better understand the different types of hearing loss to identify who is most at risk of both worsening hearing loss but also other associated medical conditions and also which patients are most likely to benefit from new treatments. The digitialisation of patient health records offers an exciting opportunity to use the latest advances in computer science methods to look at large amounts of hearing health patient data and answer these questions. Another key part of this project will look at clinical photographs of the ear drum. Access to trained specialists who can assess the appearance of ear drums is limited in the community and there are often long waits for referrals to specialty ENT services. This situation is even worse globally in resource-poor countries. To address this problem, we propose to develop an automated programme that analyse photographs of the ear drum. The clinical images will also be used to assess whether changes in the ear drum could signal the presence of vascular disease and diabetes, much like retinal screening is performed in the eye. The ear is a more readily accessible area than the eye and could provide an easy and cost-effective site for screening. Methods We will create a store of patient data that has been collected routinely as part of standard NHS clinical care. This will include demographic details, test results, measurements, and details of medical conditions. A powerful computer programme will be used to analyse this data and describe different types of hearing loss as well as how these hearing loss types change over time. We will perform further analysis to identify links between these hearing loss subtypes and other medical conditions including dementia, diabetes, stroke and high blood pressure. For the second part of this study, we will use pictures of ear drums captured by a new medical device to develop and train a computer programme that can identify and grade the key components of an ear drum that are assessed by ENT specialists. We will use this programme alongside supplied patient details to explore whether there are changes in the ear drum that can predict the presence of diabetes and heart disease. Anticipated Outcomes The key aim of this research is to better understand the natural history of hearing loss. Identifying patients who are at higher risk of developing severe hearing loss is important for resource planning, patient counselling and identifying people who are most likely to benefit from emerging treatments or clinical trials. Identifying new associations between hearing loss and other conditions could identify patients who are "at risk" prompting earlier diagnosis and act as an opportunity for early intervention and the promotion of lifestyle modifications to divert or delay the onset of such conditions through behavioural change.

Modern cancer treatment is largely a combination of 3 techniques: surgery, chemotherapy and radiotherapy. Radiotherapy uses beams of X-rays to irradiate the tumour from many different directions. The effect is to kill the cancer by depositing as much radiation dose in the tumour as possible, whilst minimising the dose to the surrounding area to spare healthy tissue. Proton therapy is a more precise form of radiotherapy that provides significant benefits over conventional X-ray radiotherapy. Protons lose energy - and therefore deposit their dose - in a much smaller region within the body, making the treatment much more precise: this leads to a more effective cancer treatment with a smaller chance of the cancer recurring. This is particularly important in the treatment of deep-lying tumours in the head, neck and central nervous system, particularly for children whose bodies are still developing and are particularly vulnerable to long-term radiation damage. The advantages of proton therapy, coupled to the falling cost of the equipment, has led to a surge in interest in proton therapy treatment worldwide: there are now over 100 centres, with this number currently doubling every 3 years. In the UK, the NHS has funded 2 full-sized proton therapy centres - at University College Hospital in London and The Christie in Manchester - to operate alongside the eye treatment facility at the Clatterbridge Cancer Centre. These will provide treatment for a much wider range of cancers, allowing more patients to be treated closer to home. Treating these cancers requires machinery that is significantly more complex than a conventional radiotherapy system. Protons are accelerated to the right energy for treatment by a particle accelerator: once the beam leaves the accelerator, it then has to be transported to the treatment rooms many metres away by a series of steering and focussing magnets. When the proton beam reaches the treatment room, it has to be delivered through a gantry to the correct place. Proton therapy gantries are enormous - more than 3 storeys tall and weighing more than a hundred tonnes - and have to rotate around the patient to deliver the beam from any angle with millimetre precision. In order to ensure that treatment with such complex machinery is carried out safely, a range of quality assurance (QA) procedures are carried out each day before treatment starts. This means checking that the proton beam is in the correct position, is the right shape and size, and travels the correct depth: this must be checked for a range of different beam positions and energies to ensure treatment is safe. These QA measurements take significant time to set up and adjust for different energies: the full procedure can take over an hour. We are developing a detector that can make faster and more accurate measurements of the proton beam size, position and range than existing systems. The detector is made of two parts. The first is a profile monitor made of two arrays of scintillating optical fibres, mounted at right angles to each other, that emit light when the proton beam passes through. This light can be measured with photodiodes to determine the beam size and position. Behind this is a detector built from layers of plastic scintillator that resembles a sliced loaf of broad. Protons passing through this scintillator stack deposit energy in each layer which is converted into light: by recording the light from each layer, the amount of energy the protons deposit along their path can be measured. Such a system provides a direct measurement of the range of protons in tissue, since the absorption of the plastic is virtually identical to human tissue. As such, the full morning beam QA procedure could be carried out in a few minutes, with an accuracy well below a millimetre in size, position and range. At the two new NHS centres, this would translate into being able to treat an extra 12-18 patients every single day.

40% of all patients in the intensive care unit (ICU) need a ventilator to support their lungs, with many associated complications. Currently the main indication of clinical deterioration is the presence/spreading of shadowing on the chest x- ray. This has many different causes (all requiring different treatments). There is a pressing need for rapid bedside tests to provide definitive diagnostic information about what is happening in the lungs themselves. Many studies have used blood markers, but in patients with multi-system disease these are not specific for the lung and the results are too slow to be useful in the rapidly-changing ICU setting. We will employ cutting-edge technology to pass a tiny optical fibre deep into the lungs of ventilated patients and spray a 'microdose' of an imaging agent that will tell us the reasons for the lung deterioration. This approach has the potential to rapidly determine, at the bedside, if the lung shadowing is due to inflammation. Such an approach could revolutionise the way we deal with the critically ill patient and provide rapid, point of care diagnostics that would help tailor the patient's management.

Hand function is crucial for almost every aspect of daily life, and even temporary impairment can have massive financial and societal implications on both patients independence and employment. The UK is currently estimated to sustain an annual incident rate of 68,000 temporary arm immobilisation cases due to orthopaedic injury, with a projection for a significant increase due to fragility fractures which are particularly impacting the rising older population. Unlike lower-limb assistive options, such as wheelchairs and crutches, there are currently no assistive technologies for temporary upper-limb immobilisation. We seek to target this unmet clinical need and offer a radically different approach to existing options for improving functionality following hand injury. To intelligently meet patient needs while supporting healing and rehabilitation of the affected hand, we propose to increase the functionality of the non-damaged hand during the immobilisation period. During the injury's acute phase, mobilising the injured hand will be painful and impractical. Thus, augmenting the unimpaired hand will immediately enhance functionality to help alleviate temporary disability. This will be done via motor augmentation using a supernumerary robotic device called the Third Thumb, developed by the project contributor Dani Clode Design. As an extra thumb prosthetic specifically designed to extend the motor abilities of an already fully functional hand, this device allows people to carry out complex daily tasks that normally require bimanual coordination. The project benefits from foundational evidence of our initial research on the neural basis of hand augmentation in healthy participants. We demonstrated that the Third Thumb device allows intuitive control, high levels of embodiment, basic levels of functionality for a lay user with minimal training (<10 minutes), and increased levels of dexterity and motor control with additional customised training. The proposed research project will prepare the development and clinical translation of this unique and easily implemented assistive technology to improve the independence of patients undergoing temporary immobilisation. In collaboration with clinical partners, we will assess the feasibility and safety of this assistive technology by providing a first bespoke prototype. To ensure patient satisfaction and a feasible implementation of our assistive technology, we will first develop a better understanding of user-experience, by documenting the daily needs of our patient group and by assessing initial device control in a broad and diverse group of naïve users. We will translate the knowledge gained through user-experience analysis into actionable insights for assistive technical development, with the aim to create a prototype tailored to our target population's diverse needs. To enhance motor capabilities, we will develop at-home training protocols for potential users to adapt according to their individual needs, to maximise their independence. Next, we will run a longitudinal trial to generate evidence for the device's safety and successful integration in healthy participants, with emphasis on the experience of 'embodiment'. Here, we will examine potential neural biomarkers for device embodiment and address possible 'side effects' of Thumb intensive use, to ensure its implementation as assistive technology is effective and risk-free. Finally, we will introduce and document Thumb use in individual patients with more complex needs (teenagers and older women) to provide a pre-clinical proof-of-concept for fluent control under dynamic real-life challenges. With our holistic approach, we aim to provide a bespoke solution to a largely unmet clinical need, with the potential to radically improve the daily functionality of the millions of individuals who experience transient hand disabilities annually around the world.

Stroke is the leading cause of adult disability in the UK. Every year 150,000 strokes occur and 54,000 of these fail to regain upper limb function, resulting in yearly personal and societal care costs of £5.5bn. These numbers will increase with the aging population; by 2040 the number of people over 65 is expected to grow by 67%. The government has termed this situation 'a ticking time bomb' and has called for innovative technology that Persons with Stroke (PwS) can use in their own homes. Functional Electrical Stimulation (FES) of muscles is a technology that has been shown to help PwS re-learn lost skills by enabling them to practice and regain lost arm movement, and in-so-doing create new nerve connections in their brain. FES works by stimulating muscles with electrical pulses via electrodes placed on the skin. Unfortunately, commercial FES systems are not suitable for intensive daily use as they are rigid and uncomfortable, and not able to assist PwS in performing the necessary precise movements because only a limited number of muscles are stimulated. In our previous research we have developed a prototype FES array on a conventional wearable fabric enabling the FES to be worn as normal clothing to achieve rehabilitation. The FES array thus is flexible, breathable and comfortable to wear, and can be scaled up to cover as many muscles as are needed. A range of precise hand functions including pinching, pointing and hand opening have been achieved by stimulating an optimised selection of electrode elements in the array. The stimulation is controlled using advanced software called "iterative learning control" which mimics the way the brain learns new skills. This controller can potentially achieve highly accurate movement by learning the optimal stimulation pattern over multiple attempts at a task. Our project will use printing to fabricate customised FES garments to precisely fit the individual's arm and specific needs. The customised FES array design will be generated by scanning the arm using a commercial 3D scanner and processing the image using software developed in this project. Each FES array will be printed on standard everyday fabric and then integrated into a piece of clothing (e.g. cuff/armband, sleeve, long sleeved T-shirt). The resulting garment will be very comfortable to wear and convenient to use every day. The FES clothing will be operated using a wireless control system combined with sensors which automatically adjust the FES to enable precise activities, such as assisting eating, washing and dressing. We will work closely with an expert user group consisting of PwS and their carers, FES engineers and healthcare professionals to produce a detailed device specification. This will provide the device requirements in terms of comfort, robustness, stimulation function and cost criteria. Following development, the device will be tested against this specification and refined throughout the project to ensure it fully meets the needs of PwS. Our technology will bring affordable, effective physical therapy into the homes of PwS, allowing them to practice goal-orientated functional activities at home without needing a carer or therapist. It thereby increases the intensity of rehabilitation without an increase in clinical contact time. This will lead to better outcomes, such as reduced impairment, greater restoration of function, improved quality of life and increased social activity. This in turn will translate to greater independence leading to less dependence on carers, and the possibility of return to work. The first application of the technology will be with PwS with upper limb impairments followed by those with lower limb impairments. The technology can also potentially be further applied to treat other neurological conditions such as spinal cord injuries and multiple sclerosis.