The addition of lead substitutes to automotive fuel and the introduction of catalytic converters have led to the appearance of several other, normally rare metals, in exhaust emissions. Over 95% of all cars now manufactured have metal-based two or three-way catalytic converters and emissions from these systems is leading to a well documented, dramatic increase in the concentration of platinum in roadside and tunnel dusts. Little information is available for some of the other rare metals such as cerium, hafnium and zirconium, which can be present in very much higher abundances than Pt in the wash coats of converters, but it is likely that they are accumulating too, probably in much greater abundances. These metals are emitted as ultra-fine reactive particles, and so are readily absorbed when inhaled and consequently are more likely to produce toxicological effects. A chance discovery that at least one of these metals, hafnium, may become incorporated into the primary genetic material (DNA) of some individuals implies that even metals which are usually innocuous can become biologically active if absorbed by the lung in this way. More importantly, this incorporation into DNA implies that they might increase the risk of lung or other cancers by altering or damaging DNA replication. Some of the metals in question (cerium and hafnium) have isotopic compositions that vary in nature and it may be possible to specifically identify the source and sink of these elements in the environment and in the human body through characteristic isotopic compositions that will 'fingerprint' their origin. To properly evaluate the risk to human health through accumulation of these metals in the environment we need to instigate a research programme to define basic information such as:- Is there evidence for accumulation of anthropogenic cerium, hafnium and zirconium consistent with the increase in some platinum group elements? What are the main environmental sources and pathways of these metals into human receptors and what are the most bioavailable forms? To what extent do these levels vary between individuals? To what extent can we distinguish sources using isotope ratio tracing? What are typical baseline levels of these metals, in human organs such as the lungs and the liver, in human blood and in DNA extracts? To what extent do the metals become mobilised and biologically active by measurement of the levels bound to DNA and certain proteins We have assembled a diverse team of scientists with environmental, biomedical, clinical and toxicological expertise that offer a very fortuitous combination of the latest analytical and extraction technology plus access to human tissue and blood samples. This cross-disciplinary team, together with a post-doctoral scientist, will be well pace to answer the above questions and hence provide preliminary data on which to base future studies and risk assessments for human health.

The human cardiovascular system consists of two large arteries: the aorta (AO), which supplies oxygenated blood to the body, and the pulmonary artery (PA), which supplies deoxygenated blood to the lungs for oxygenation. In healthy individuals, the pressure in the AO is significantly higher than the pressure in the PA. Pulmonary artery hypertension (PAH) is a disease in which the PA pressure is abnormally elevated and is classified as one of the most devastating disorders by the pulmonary artery association UK. This is evidenced by a mean survival time after diagnosis of less than 30 months in adults and less than 12 months in children. A recently proposed treatment for severe PAH, i.e. the case when PA pressure is higher than the pressure in AO, is to create a connection, known as the Potts shunt, between the PA and the AO. Just as a connection between two pipes carrying fluids with high and low pressures will lead to a reduction of pressure in the high-pressure pipe and an increase of pressure in the low-pressure pipe, the idea is that a Potts shunt can lead to a reduction of PA pressure in severe PAH patients. This reduction in PA pressure is desirable but will also result in mixing of oxygenated and deoxygenated blood, an undesirable effect. Clinical experience has shown favourable results of this treatment in some patients and unfavourable in others, which is attributed largely to a reduction in cardiac output, the total volume of blood ejected by the heart in one cardiac cycle. This project aims to develop computational models to assess three measures of Potts shunt treatment: 1) reduction of pulmonary artery pressure, 2) mixing of oxygenated and deoxygenated blood, and 3) reduction in cardiac output. Through the computational models, this project will assess the mechanisms behind the success/failure of Potts shunt in relation to the above measures. The end-product will be a computer model which, given a new patient, can determine if a Potts shunt is likely to succeed in the patient. Furthermore, technology to optimise the design of Potts shunt for each patient individually, such that maximal clinical benefit is achieved, will be developed.

Worldwide, there are over three million people living with upper-limb loss. Recent wars, industrialisation in developing countries and vascular disease, e.g. diabetes, have caused the number of amputations to soar. Adding to this population each year, one in every 2,500 people are born with upper-limb reduction. Advanced prostheses can play a major role in enhancing the quality of life for people with upper-limb loss, however, they are not available under the NHS. Notably, many people with traumatic limb loss are otherwise physically fit. If they are equipped with advanced prostheses and treated to recover psychologically, they can live independently, with minimal need for social support, return to work and contribute to the economy. There are a plethora of underlying reasons that limit wide clinical adoption of advanced prosthetic hands. For instance, surveys on their use reveal that 20% of upper-limb amputees abandon their prosthesis, with the primary reason being that the control of these systems is still limited to one or two movements. In addition, the process of switching a prosthetic hand into an appropriate grip mode, e.g. to use scissors, is cumbersome or requires an ad-hoc solution, such as using a smart phone application. Other reasons include: users finding their prosthesis uncomfortable or unsuitable for their needs. As such, everyday tasks, such as tying shoe-laces, are currently very challenging for prosthetic hand users. These functional shortcomings, coupled with high costs and lack of concrete evidence for added benefit, have emerged as substantial barriers limiting clinical adoption of advanced prosthetic hands. The long-term aim of this cross-disciplinary programme is to develop, and move towards making available, the next generation of prosthetic hands that can improve the users' quality of life. Our underlying scientific novelty is in utilising users' capability of learning to operate a prosthesis. For instance, we examine the extent to which the activity of muscles can deviate from natural patterns employed in controlling movement of the biological arm and hand and whether prosthesis users can learn to synthesise these functional maps between muscles and prosthetic digits. Basing this approach upon our pilot data, we hypothesise that practice and availability of sensory feedback can accelerate this learning experience. To address this fundamental question, we will employ in-vivo experiments, exploratory studies involving able-bodied volunteers and pre-clinical work with people with limb loss. The insight gained from these studies will inform the design of novel algorithms to enable seamless control of prosthetic hands. Finally, the programme will culminate with a unifying theory for learning to control prosthetic hands that will be tested in an NHS-approved, pre-clinical trial. Maturing this approach into a clinically-viable solution needs a dedicated team of engineers and scientists as well as a consortium of users, NHS-based clinicians and healthcare and high-tech industries. With the flexibility that a Healthcare Technologies Challenge Award affords me, I will be able to nurture and grow sustainably my multi-disciplinary team. In addition, this flexible funding will enable to focus on a converging research programme with the ultimate aim of providing prosthetic solutions that enhance NHS-approved clinical patient outcome measures significantly. Within this programme, I will identify and bring together the engineering, scientific, clinical, ethical and regulatory elements necessary to form a recognised national hub for the development of next-generation prosthetics. This work will provide the foundations for my 15-year plan to establish the Centre for Bionic Limbs. The origin of this Centre will be to act as a mechanism to safeguard engineering and scientific innovations, increase value, and accelerate transfer into commercial and clinical fields.

Worldwide, there are over three million people living with upper-limb loss. Recent wars, industrialisation in developing countries and vascular disease, e.g. diabetes, have caused the number of amputations to soar. Adding to this population each year, one in every 2,500 people are born with upper-limb reduction. Advanced prostheses can play a major role in enhancing the quality of life for people with upper-limb loss, however, they are not available under the NHS. Notably, many people with traumatic limb loss are otherwise physically fit. If they are equipped with advanced prostheses and treated to recover psychologically, they can live independently, with minimal need for social support, return to work and contribute to the economy. There are a plethora of underlying reasons that limit wide clinical adoption of advanced prosthetic hands. For instance, surveys on their use reveal that 20% of upper-limb amputees abandon their prosthesis, with the primary reason being that the control of these systems is still limited to one or two movements. In addition, the process of switching a prosthetic hand into an appropriate grip mode, e.g. to use scissors, is cumbersome or requires an ad-hoc solution, such as using a smart phone application. Other reasons include: users finding their prosthesis uncomfortable or unsuitable for their needs. As such, everyday tasks, such as tying shoe-laces, are currently very challenging for prosthetic hand users. These functional shortcomings, coupled with high costs and lack of concrete evidence for added benefit, have emerged as substantial barriers limiting clinical adoption of advanced prosthetic hands. The long-term aim of this cross-disciplinary programme is to develop, and move towards making available, the next generation of prosthetic hands that can improve the users' quality of life. Our underlying scientific novelty is in utilising users' capability of learning to operate a prosthesis. For instance, we examine the extent to which the activity of muscles can deviate from natural patterns employed in controlling movement of the biological arm and hand and whether prosthesis users can learn to synthesise these functional maps between muscles and prosthetic digits. Basing this approach upon our pilot data, we hypothesise that practice and availability of sensory feedback can accelerate this learning experience. To address this fundamental question, we will employ in-vivo experiments, exploratory studies involving able-bodied volunteers and pre-clinical work with people with limb loss. The insight gained from these studies will inform the design of novel algorithms to enable seamless control of prosthetic hands. Finally, the programme will culminate with a unifying theory for learning to control prosthetic hands that will be tested in an NHS-approved, pre-clinical trial. Maturing this approach into a clinically-viable solution needs a dedicated team of engineers and scientists as well as a consortium of users, NHS-based clinicians and healthcare and high-tech industries. With the flexibility that a Healthcare Technologies Challenge Award affords me, I will be able to nurture and grow sustainably my multi-disciplinary team. In addition, this flexible funding will enable to focus on a converging research programme with the ultimate aim of providing prosthetic solutions that enhance NHS-approved clinical patient outcome measures significantly. Within this programme, I will identify and bring together the engineering, scientific, clinical, ethical and regulatory elements necessary to form a recognised national hub for the development of next-generation prosthetics. This work will provide the foundations for my 15-year plan to establish the Centre for Bionic Limbs. The origin of this Centre will be to act as a mechanism to safeguard engineering and scientific innovations, increase value, and accelerate transfer into commercial and clinical fields.

Biofilms are microbial cells embedded within a self-secreted extracellular polymeric substance (EPS) matrix which adhere to substrates. Biofilms are central to some of the most urgent global challenges across diverse fields of application, from medicine to industry to the environment and exert considerable economic and social impact. For example, catheter-associated urinary tract infections (CAUTI) in hospitals has been estimated to cause additional health-care costs of £1-2.5 billion in the United Kingdom alone (Ramstedt et al, Macromolec. Biosci. 19, 2019) and to cause over 2000 deaths per year (Feneley et al, J. Med. Eng. Technol. 39, 2015). To combat biofilm growth on surfaces, chemical-based approaches using immobilization of antimicrobial agents (i.e. antibiotics, silver particles) can trigger antimicrobial resistance (AMR), but are often not sustainable. Alternatively, bio-inspired nanostructured surfaces (e.g. cicada wing, lotus leaf) can be used, but their effects often may not last. A recent innovation in creating slippery surfaces has been inspired by the slippery surface strategy of the carnivorous Nepenthes pitcher plant. These slippery surfaces involve the impregnation of a porous or textured solid surface with a liquid lubricant locked-in to the structure. Such liquid surfaces have been shown to have promise as antifouling surfaces by inhibiting the direct access to the solid surface for biofilm attachment, adhesion and growth. However, the antibiofilm performance of these new liquid surfaces under flow conditions remains a concern due to flow-induced depletion of lubricant. Here we propose a novel anti-biofilm surface by creating permanently bound slippery liquid-like solid surfaces. Success would transform our understanding about bacteria living on surfaces and open-up new design paradigms for the development of next generation antibiofilm surfaces for a wide range of applications (e.g. biomedical devices and ship hulls). To enable the successful delivery of this project, it requires us to combine cross-disciplinary skills ranging from materials chemistry, physical and chemical characterisations of materials surfaces, nanomechanics, microbiology, biomechanics, to computational mechanics. The project objectives well align with EPSRC Healthcare Technologies Grand Challenges, addressing the topics of controlling the amount of physical intervention required, optimizing treatment, and transforming community health and care. In parallel, we shall contribute to the advancement of Cross-Cutting Research Capabilities (e.g. advanced materials, future manufacturing technologies and sustainable design of medical devices) that are essential for delivering these Grand Challenges. In particular, this research will employ nanomechanical tests to determine bacteria adhesion and microfluidics techniques for biofilm characterisation, which enables us to create novel approaches in computational engineering through the formulation and validation of sophisticated numerical models of bacteria attachment and biofilm mechanics.