Globally, 15 million people suffer a stroke every year, causing 6 million deaths and leaving another 5 million permanently disabled, which makes stroke the second leading cause of disability. In the Europe, it is the most common cause of morbidity and long-term disability, and has significant socioeconomic consequences for patients, their partners and society. Thus far, upper limb weakness remains the biggest and most challenging disability, due to the complexity of movement required in daily living and its generally slower and less complete recovery. More than 50% of stroke survivors still have upper extremity hemiparesis one year after stroke. Neuro rehabilitation is the main approach to improve upper extremity motor outcome, and previous studies have demonstrated that patients can regain considerable motor functions after intensive training. With the number of people surviving a stroke soaring, more and more rehabilitation programs are delivered with minimal involvement of a physiotherapist due to limited resource available, and the success of this approach depends on the accurate assessment of stroke patients’ movement impairment. In collaboration with with the National Demonstration Centre in Rehabilitation Medicine, Leeds Teaching Hospitals NHS Trust, my vision is therefore to establish a comprehensive, quantitative, objective and personalised Motor Impairment Index (MII), via benchmarking the impaired arm movement to healthy arm mirrored exercise to quantify the motor impairment. This approach will increase the likelihood of successful rehabilitation leading to improved quality of life for millions of people affected by stroke. This application focuses on developing innovative healthcare technologies for stroke patients; but it could also potentially benefit millions of people with conditions such as multiple sclerosis, brain tumours and spinal cord injury, as well as people with musculoskeletal conditions or trauma.

Oral administration, e.g. tablets and capsules, is the preeminent dosage-form for most solid drug compounds. Designing and formulating drugs for which the rate-limiting step of drug release is dissolution of crystalline solids remains a persistent challenge, this is due to our insufficient understanding of the optimal dissolution characteristics from first principles. The current dissolution model, still based on the Noyes-Whitney equation (1897), does not consider the dissolution on the different morphological faces of crystal, nor take into account for the detailed molecular diffusion through the stagnant solution layer around the crystal surfaces. The project will employ optical interferometric microscopic techniques to characterise single, faceted-crystal dissolution rates associated with the morphology and size. This will also relate to the surface chemistry of the crystal (such as crystal surface structure and interaction with the solution, e.g. hydrophilicity), fluid characteristics (e.g. solution concentration, viscosity), and solution boundary concentration gradient and diffusion co-efficient through it. This would significantly improve our understanding of crystal dissolution and hence provide a scientific based for the prediction of drug dissolution and industrial formulation design. Aims: The ultimate aim is to develop a model that provide an accurate description for drug dissolution behaviour related to pharmaceutical ingredient solid particles of formulated tablets, which underpins the design and optimisation of solid dosage forms. Objectives: Commissioning of the interferometry equipment of Michelson and Mach Zenhder setups. Growing single crystals of selected drug compounds into different sizes for dissolution tests. Measuring dissolution rate as a function of morphologic face, size and degree of solution undersaturation. Measuring solution stagnant boundary layer thickness and solute concentration gradient. Developing the dissolution model in association with surface chemistry and solution characteristics. Methodology: For the project, the drug crystal/solvent systems will be selected to representing the contrast in surface chemistry of dissolution. Single crystal samples with well-defined hkl morphology will be prepared by growing crystals to different sizes (from micro meter to millimetre). Dissolution rates of these crystals' morphological faces are accurately measured in the direction normal to the incidence beam via observation of the light interference rings as a function of crystal size, solution type and pH, and level of undersaturation, using Michelson interferometer. These results will be respectively compared against the measurements of the thickness and concentration profile across the solution boundary surrounding the dissolving crystal faces using Mach Zenhder interferometric setup. The Mach Zenhder interferometer applies an incidence beam parallel to the crystal hkl face. The light interference fringes is visualised based on the solution refractive-index variation as a function of solution concentration and hence interpreted into the solution concentration gradient across the boundary layer of the specific hkl faces. Using the concentration gradient profile in the boundary layer and the dissolution rate in terms of mass of diffusion, the new mass transfer kinetic model can be established associated with chemistry and physics of the crystal/solution systems.

The oceanic carbon cycle is key for regulating the Earth system because, in sediments and seawater, the balance between the degradation and preservation of organic carbon (OC) exerts a first order control on atmospheric CO2 and O2. In sediments, OC is preserved over millions of years, while in seawater, a dissolved form of recalcitrant OC has been recently recognised as critical to OC storage over anthropogenic timescales. Both sedimentary and seawater OC are derived from living organisms, and should therefore be easily degraded. Their persistence is therefore profoundly puzzling. Quite simply we do not know how or why OC is preserved. A long-standing hypothesis suggests that protection of OC inside minerals might account for the vast OC stores preserved in sediments. In a NEW hypothesis, based on recent work by the PI and proposed here for the first time, the interaction of OC with minerals might ALSO account for the even larger stores of dissolved OC preserved in seawater. Together these concepts could revolutionise our understanding of OC degradation and preservation, but the extent to which minerals preserve OC in sediments and seawater is (still) unknown, largely because the mechanisms that control how OC interacts with minerals are almost entirely unconstrained. MINORG will quantify the role of minerals in the preservation of OC for the first time, by combining cutting-edge molecular-level techniques with the first ever comprehensive and fully integrated experimental and modelling campaign, to determine in unprecedented detail the exact mechanisms responsible for the interaction of OC with minerals, and its subsequent degradation and preservation behaviour. MINORG hypothesises that minerals play a MAJOR role in the preservation of OC, in both its sedimentary and seawater forms, and is uniquely poised to test this. This project will majorly contribute to our quantitative understanding of the oceanic carbon cycle, and so to predicting current climate change.