Osteoarthritis affects over eight million people in the UK alone, with nearly three quarters of patients reporting some form of constant pain. Treatment for arthritis is estimated to cost the UK healthcare system over £10 billion per year, with significant additional societal costs for lost working hours and welfare payments. Although hip and knee replacement surgeries are considered successful, these treatments are not suitable for all patients and some devices fail early, requiring costly and less successful revision surgery. There are over 15,000 revision surgeries performed in the UK alone each year. Younger and more active patients, as well as rising numbers with obesity, are placing greater demands on these treatments: implants need to last for longer and withstand more extreme loading than ever before. There is evidence that both individual patient biomechanics and surgical choices influence the outcomes of these treatments. Improved outcomes, particularly for more challenging patient groups, can only be achieved by better matching the treatment to the functional requirements of the individual patient. This proposal will bring together complementary research expertise from two of the world's leading research institutes in the field to build the evidence needed to enable treatments for osteoarthritis to be better tailored to individual patient needs. The Institute of Medical and Biological Engineering at the University of Leeds has developed unique capability and expertise to evaluate artificial and natural joints. These include the world's largest academic facility for experimentally testing joint replacements, as well as computational modelling methods to simulate how implants perform in the body. These capabilities enable the mechanical performance of implants to be evaluated under a range of different conditions, for example to study how the implant wears over time or becomes damaged with usage. The Center for Orthopaedic Biomechanics at the University of Denver has developed world-leading capability in measuring patient joint mechanics in vivo, including methods of imaging patient joints as they undertake different activities, and parallel computational methods for deriving biomechanical information. These methods enable the forces and motions on an individual patient's hip or knee joints to be derived and, by collecting data on many patients, examine how these differ from one individual to another. By combining the expertise across both groups, this Centre-to-Centre Research Collaboration will enable relationships to be developed between an individual patient's characteristics (e.g. their anatomy and how they load their joints) and the mechanical performance of the implant. Specifically, in the hip we will combine methodologies developed at the two centres to evaluate how patient and surgical factors affect the risk of early failure in hip replacements due to the device components pushing into each other or the surrounding bone (impingement), or the way the components are aligned. We will also examine how different choices of implant can influence the outcomes. In the knee, we will combine methodologies to identify how patient factors (such as the anatomy of the knee and the way it is loaded during different activities) affect early-stage treatments for knee osteoarthritis. We will also examine the effects of a greater range of activities, such as squatting and stair climbing, on the outcomes of knee replacements. These studies will bring together different methodologies and build new pathways for acquiring and sharing data that can be adopted more widely and applied to other musculoskeletal systems in the future. The work will build the evidence needed to improve hip and knee implant design, inform clinical decision-making, enhance patient quality of life and reduce early complications.

Volcanic injections of sulphur brighten the stratospheric aerosol layer with major eruptions inducing periods of strong cooling within global mean surface temperature trends. The stratospheric ozone layer shields us from harmful UV radiation, and accurately predicting how it will recover relies on predicted changes in stratospheric aerosol and polar clouds. The MeteorStrat project addresses two key knowledge gaps that limit current predictive capability of composition-climate models, both associated with the effects from the continual supply of meteoric material entering the upper atmosphere. Firstly, recent in-situ observations have confirmed findings from the late 1990s that most particles in the stratospheric aerosol layer contain refractory core of meteoric origin, posing a major challenge to the current generation of interactive stratospheric aerosol models. Secondly, how the polar stratospheric clouds, that provide the medium by which emissions of compounds such as CFCs leads to polar ozone loss, form in the Arctic has remained a persistent uncertainty, limiting the confidence of model predictions for how the ozone layer will recover. The MeteorStrat team have made two breakthrough research findings that uniquely enable to address long-standing questions in stratospheric aerosol and PSC science. Firstly, our global model "meteoric smoke interaction experiments" show major effects from extra-terrestrial material, the meteoric inclusions radically altering the vertical distribution of sulphuric particles, challenging how models predict changes in the stratospheric aerosol layer. Secondly, our laboratory PSC freezing experiments reveal that rather than ablation-generated smoke particles (which were found to be poor NAT nuclei), it is an inclusion of non-ablated meteoric fragment particles that may explain how many NAT particles nucleate in the Arctic. This project builds on these exciting research findings with two hypotheses addressing the overarching aim to assess how cosmic dust influences the composition of the stratosphere. A. That meteoric-sulphuric particles are larger, with shorter stratospheric residence times, has important consequences for how models predict decay from volcanic enhancement B. The mechanism by which solid nitric acid PSCs form in the Arctic can finally be explained by the non-ablated meteoric fragments providing the preferential NAT nuclei We will combine our internationally-leading laboratory and modelling capabilities to test these hypotheses. Our workplan addresses the following 5 related science questions: 1. How far do the high-latitude source meteoric-sulphuric particles extend to lower latitudes and how variable is their mid-latitude abundance across different seasons and years? 2. Do the larger meteoric-sulphuric particles effect a faster volcanic decay timescale and if so what are the implications for the surface cooling attributed to volcanic eruptions? 3. What is the source flux and size distribution of the non-ablated "meteoric fragment" input and how do smoke or fragments transform into Junge layer meteoric-sulphuric particles? 4. How do the distinctly composed meteoric fragments facilitate NAT freezing and what are the implications of the laboratory findings compared to smoke-driven parameterizations? 5. Can meteoric influence explain observed PSCs and how is Arctic ozone loss enhanced? A key philosophy of the project involves gathering in situ and satellite measurement datasets to ensure model predictions are observationally-constrained and calibrated to maximise confidence in research findings. The project will provide the UK Earth System Model with vital capability to simulate future changes to the stratosphere, in particular for the effects from volcanic and potential stratospheric sulphur or particle geoengineering.

Our vision is that patients with knee pain receive the right treatment at the right time. In the UK, one third of people aged over 45 have sought treatment for osteoarthritis, and the disease costs the NHS over £5 billion per year. The knee is the most common site for osteoarthritis, with over four million sufferers in England alone. The aging population with expectations of more active lifestyles, coupled with the increasing demand for treatment of younger and more active patients, are challenging the current therapies for knee joint degeneration. There is a major need for effective earlier stage interventions that delay or prevent the requirement for total knee replacement surgery. There are large variations in patients' knees and the way that they function, and it is important that this variation is taken into account when treatments are developed, so that the right treatment can be matched to the right patient. Through this ambitious programme of research we will develop novel testing methods that combine laboratory-based simulation and computer modelling to predict the mechanical performance of new therapies for the knee and enable their design and usage to be optimised. Importantly these tests will take into account the variation in patients' anatomy and knee biomechanics, as well as variations in device design and surgical technique. This will enable different therapies, or different variants of a device, to be matched to different patient groups. The tools will be applied to existing treatments using clinical data to help validate that our model predictions are correct. The outcomes will better define which patients will benefit from a particular intervention and help optimise their usage. We will then apply the methods to new and emerging treatments, including regenerative devices, so that they can be tested and optimised before costly clinical trials take place. We will use these examples as case studies to demonstrate how the new testing methods can optimise the products before they reach the patient, and we will work with industry, standards agencies and regulators to promote the adoption of these methods across the sector. This programme will benefit patients, the NHS and the growing UK industry and science base that are developing new therapies for the knee.