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.

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.

This proposal is to conduct rich ethnographic fieldwork, and a follow-up period of stakeholder reflections, within a palliative care team based within a large NHS hospital and its surrounding neighbourhood. There is currently a great deal of interest in how the NHS as a whole is having to make treatment decisions at both the policy and individual level by taking into account diverse criteria and values. As part of this, a lot of debate has focused on so-called 'over-treatment' and high-profile cases of medical neglect. However, in practice, and between these two extremes, medical care regularly involves more modest practices of simply not intervening or of withdrawing treatment. For example, these 'non-interventions', as we currently call them, might include reducing or removing medications or other therapies (including fluid provision), withholding treatments before they have started, or simply waiting to observe how a patient's condition develops. The study will consequently explore the many forms and occasions when medical staff - doctors, nurses and other care workers - opt to not actively intervene. Paradoxically, this mode of 'not intervening' is, from the palliative team's standpoint, a valid and important variant of medical intervention, yet is regularly perceived as withholding or denying the patient services or treatment. We will do this by focusing on palliative care, as previous research has suggested that there is a particular shift in the frequency and kinds of interventions and 'non-interventions' considered when patients are eventually referred to this specialism. Through field-based research (support from our NHS project partners already agreed, subject to funding) we will seek to observe both the overt and more implicit ways in which care is done. Observations will be supplemented with interviews with staff, and patient case studies (including interviews with patients and their identified important others, e.g. relatives and/or carers). In so doing, we will be able to trace the multiple, and potentially competing, values and expectations that underlie everyday care and the extent to which not intervening complements or clashes with the common, default, biomedical approach of active and aggressive management. By drawing on anthropological theories and methods we will analyse the way this alternative 'logic of care' emerges in practice, and how people themselves differentiate it from both neglect and the more heroic imperative to always act. Although instances of not intervening are regularly described and defined as simply the opposite to the usual imperative to always clinically intervene, we wish to contextualise these occasions within the everyday care that is provided, and examine the extent to which different values and criteria are being drawn on, and ultimately whether the patient and their status are thereby constructed differently. The data generated through this stage will be used in collaborative events to stimulate discussion and co-produce ways of re-framing 'non-interventions' as distinct from discourses of failing or neglect. Engaging with current debates in anthropology and the social sciences more broadly, its ethnographic focus will thereby contribute to contemporary interest concerning social practice by highlighting the ways in which not being present and not doing can be both active and meaningful. In addition to traditional academic outputs, we will produce online interactive assets based on case studies to promote exploration and discussion of the issues raised by the study. In doing so, the research will contribute to current debates not only about palliative and end of life care, but the role of medical interventions more broadly. The project will seek to re-conceptualise instances of medical 'non-intervention' as integral forms of biomedicine, and so contribute to current debates about what appropriate clinical practice and good care should be.

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 reduced cost of the equipment, has led to a surge in interest in proton therapy treatment worldwide: there are now over 70 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. A significant fraction of this time is spent verifying that the proton beam travels the correct depth and is carried out for several different energies: protons are counted at different depths in a material, like ware, that mimics human tissue. These QA measurements of the proton range take significant time to set up and adjust for different energies: the full procedure can take over an hour. The focus of this project is to develop a detector that can make faster and more accurate measurements of the proton range than existing systems. The detector is built from layers of plastic scintillator that has the same density as water and 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, a measurement of the proton range for multiple energies would allow the complete morning energy QA procedure to be carried out in a few minutes, with an accuracy of less than a millimetre. At the two new NHS centres, this would translate into being able to treat an extra 12-18 patients every single day. A prototype detector is being assembled and tested at UCL with the intention to develop a full commercial system that can make range QA measurements with the necessary speed and accuracy.

Over 3 million people in the UK suffer from cardiovascular disease causing over 150,000 premature deaths in people under the age of 75. Restriction of blood flow and blockage of blood vessels surrounding the heart leads to interruption of the blood supply to the heart muscle causing heart cells to die. The oxygen shortage, if left untreated can cause damage or death of the heart muscle resulting in heart attack or complete heart failure. Narrowing of the blood vessels in the legs can lead to blockage, amputation and limb loss if left untreated. Patients requiring amputation face a diminished quality of life and severe disability. The primary goal is to restore at least one straight line of blood flow by using a stent depending on the degree of obstruction. The application of stenting is carried out using a minimally invasive approach. A stent is a small mesh tube that is inserted using a catheter, and is deployed at the same time as a balloon is inflated across the diseased vessel wall. The stent acts as a scaffold to hold open the artery to restore blood flow. However, severe healthcare concerns have been raised with current stents, which release drugs through localised allergic reactions, chronic swelling (inflammation) and repeat episodes of thrombosis (or blood clotting), which requires a lifetime prescription of anti-platelet and blood thinning medication causing unwanted side effects followed by repeat surgery. To overcome the current problems with stenting, we plan to build upon our knowledge and expertise to deliver a new generation of stents by developing two products: 1) a novel surface coating with tiny particles embedded in a polymer or plastic coating called nanocomposite polymers, and 2) inclusion of capture antibodies (present on the surface of cells) in to the coating layer to capture stem cells from the circulating blood and converting it to endothelial cells from shear flow, the endothelial is type cells cover entire our cardiovascular system , to protect from blood thrombosis. The nanocomposite polymers have already undergone extensive testing in the laboratory, and in animals demonstrating that the polymer can be potentially used safely in humans. For example, we developed a range of surgical implants using nanocomposite polymers with a number of successful outcomes, such as the world's first synthetic wind pipe over 2.5 years ago and the patient is doing very well, 6 tubes that drain the tears (lacrimal duct) have been carried out in patients to date, and coronary artery bypass graft using same materials has started at Heart Hospital, heart valves at the preclinical. We have already optimised the polymer coating for stents, and in this study our plan is to carry out a final assessment of coated stents and compare them with currently used stents (as product 1). Pre-clinical animal studies will be used to evaluate their effectiveness application in humans. The development of product 2 is at the proof-of-principle stage. Here, we carry out preliminary tests using antibodies (raised against circulatory stem cells in the blood) incorporated in to the polymer coating for capturing stem cells from the blood, and perform tests to obtain sufficient data to apply for funding towards pre-clinical studies. This proposal will enable us to test polymer coated stents in preparation for first-in-man studies after consultation with the MHRA (UK regulatory agencies) and FDA. We will then be in a strong position to apply for funding towards clinical trials, which can be implanted in humans. The development of a new generation of nanocomposite polymer coated stents, which prevent thrombosis along with the inclusion of stem cell capture technology to enhance endothelisationcells would have a significant impact on the global economy, as individuals affected will be active in the workforce for longer, enjoy a greater quality of life and reduce the strain on vital healthcare resources.