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The APPLE COPD-ICON2 trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) without prior history of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the predefined cut-off of platelet inhibition measured using the Multiplate test in COPD patients. Eligible patients were randomised to aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only for 6 months. The primary outcome comprises inhibition (binary response) of arachidonic acid- (ASPI test, cut-off

This thesis adopts a broad qualitative standpoint. It examines police involvement in partnerships before and after the implementation of the Crime and Disorder Act, 1998, legislation which mandated the police to work in partnership. A case-study of Staffordshire Police explores experiences of officers working in partnerships pre and post 1998. The research is used to provide insights into the complexity that is partnership, which has wider applicability beyond policing. The thesis examines also the concept and specific mechanisms of policing in partnership that have, in the main, been championed by successive government administrations since New Labour in the late 1990s and are now largely assumed as being an 'effective and efficient' way of working.\ud \ud The thesis identifies an important hitherto strangely underexplored fact, namely: that the foundational policy document, which framed the Crime and Disorder Act mandating police-partnerships, the Morgan Report (1991), produced zero-evidence as to the efficacy of the partnership approach it advocates. Despite being unevidenced, the Morgan Report set in motion a national framework, bureaucratization and professionalization of partnerships. Consequently, there now exists a complex web of professional clustering’s around pre-defined problems. Significantly, the research identifies, that the formality of partnership has encouraged the police to withdraw from elements of their pre-Morgan service and care functions. Equally, partnership has little or no connection to current policing strategy. More recently Police and Crime Commissioners provide a new dynamic to partnership governance and their increasing 'influence' is being felt. However, government fiscal austerity has shifted contemporary partnership discourse with evidence presented of organizations withdrawing support and re-entrenching core activity. The thesis concludes by framing a new conceptualization for assessing partnership effectiveness.

Introduction: The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD. Methods and analysis: Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol–five dimensions–five levels of perceived problems (EQ5D-5L), St. George’s COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale. Ethics and dissemination: The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals. Trial registration number: ISRCTN43245574; Pre-results.

A physical model of the bladder has been used to study the process of urinary catheter encrustation. Techniques have been devised for the preparation of sections through these encrustations in situ on the luminal surfaces of catheters and for mapping the distribution of calcium and magnesium in the biofilms. Transmission electron microscopy on these sections showed struvite-like crystals lying in the matrix and in direct contact with the catheter surface. Calcium phosphate ("bioapatite") was distributed throughout the film and many of these amorphous particles appear to have cells at their cores. Freeze-substituted sections of biofilms also showed electron dense materials around cell-like shapes and X-ray mapping and X-ray scanning transmission microscopy on the catheter biofilms also indicate that mineralization occurs around the bacterial cells. These observations suggest that in catheterized bladders infected by Proteus mirabilis, bacteria and crystals formed in the urine, adhere to the catheter. Further colonization and growth of the cells on the catheter and crystal surfaces produces the alkaline biofilm which provides the conditions for continued encrustation. The binding of crystals directly onto the catheter and the subsequent bacterial colonization of these crystals has implications for attempts to prevent encrustation by manufacturing catheters from biomaterials impregnated or coated with antibacterials.